点击显示 收起
【关键词】 pathways
Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
ABSTRACT
ANG II induces a rise in cytosolic Ca2+ ([Ca2+]i) in vascular smooth muscle (VSM) cells via inositol trisphosphate receptor (IP3R) activation and release of Ca2+ from the sarcoplasmic reticulum (SR). The Ca2+ signal is augmented by calcium-induced calcium release (CICR) and by cyclic adeninediphosphate ribose (cADPR), which sensitizes the ryanodine-sensitive receptor (RyR) to Ca2+ to further amplify CICR. cADPR is synthesized from -nicotinamide adenine dinucleotide (NAD+) by a membrane-bound bifunctional enzyme, ADPR cyclase. To investigate the possibility that ANG II activates the ADPR cyclase of afferent arterioles, we used inhibitors of the IP3R, RyR, and ADPR cyclase. Afferent arterioles were isolated from rat kidney with the magnetized microsphere and sieving technique and loaded with fura-2 to measure [Ca2+]i. In Ca2+-containing buffer, ANG II increased [Ca2+]i by 125 ± 10 nM. In the presence of the IP3R antagonists TMB-8 and 2-APB, the peak responses to ANG II were reduced by 74 and 81%, respectively. The specific antagonist of cADPR 8-Br ADPR and a high concentration of ryanodine (100 μM) inhibited the ANG II-induced increases in [Ca2+]i by 75 and 69%, respectively. Nicotinamide and Zn2+ are known inhibitors of the VSM ADPR cyclase. Nicotinamide diminished the [Ca2+]i response to ANG II by 66%. In calcium-free buffer, Zn2+ reduced the ANG II response by 68%. Simultaneous blockade of the IP3 and cADPR pathways diminished the [Ca2+]i response to ANG II by 83%. We conclude that ANG II initiates Ca2+ mobilization from the SR in afferent arterioles via the classic IP3R pathway and that ANG II may lead to activation of the ADPR cyclase to form cADPR, which, via its action on the RyR, substantially augments the Ca2+ response.
calcium-induced calcium release; ryanodine; vascular smooth muscle; nicotinamide
IT IS BECOMING generally accepted that agonist stimulation of G protein-coupled receptors, formation of IP3, and activation of IP3 receptors (IP3R) cause release of Ca2+ of very short duration from the endoplasmic and sarcoplasmic reticulum (ER/SR) (3, 26). The Ca2+ signal, likely initiated by IP3, is then amplified and sustained by activation of a ryanodine receptor (RyR) by the increase in cytolsolic Ca2+ ([Ca2+]i). This process, known as calcium-induced calcium release (CICR), is enhanced by cyclic adeninediphosphate ribose (cADPR) and possibly by IP3 as well (22, 26, 53). cADPR, discovered by H. C. Lee in 1989 in sea urchin eggs (38), is synthesized from -nicotinamide adenine dinucleotide (NAD+) by a bifunctional membrane-bound enzyme, ADP ribosyl cyclase, in a wide variety of eukaryotic cells (24, 36). cADPR activates a RyR (40, 54) and, in conjunction with calmodulin, sensitizes a RyR to Ca2+, thereby augmenting CICR (14, 23, 34).
Evidence for the presence of an ADPR cyclase and for a role of cADPR in Ca2+ signaling has been established in a large number of mammalian cell types, including pancreatic islet cells, cardiac myocytes, trachea, intestinal longitudinal muscle, lymphocytes, sympathetic neurons, salivary and lacrimal gland cells, and hepatocytes (24, 36). Only recently, however, has a role for cADPR been investigated in vascular smooth muscle (VSM). In membrane preparations of aorta (13, 53), renal microvessels (39), coronary arteries (31, 52, 55), and pulmonary artery (16), evidence for ADPR cyclase activity has been demonstrated. Measurement of changes in [Ca2+]i in response to cADPR has been made in permeabilized renal VSM cells (39). To our knowledge, there have been no Ca2+ studies examining the activation of the cADPR pathway in intact fresh afferent arterioles and no studies exploring the effect of ANG II on this particular pathway in VSM of any origin.
The ADPR cyclase of VSM has several unique properties that distinguish it from the CD38 ADPR cyclase of nonvascular cells. In contrast to the CD38 enzyme of sea urchin eggs, aplysia, and HL-60 cells, in which Zn2+ enhances the activity of the enzyme, Zn2+ inhibits the cyclase of rat aortic VSM cells (13). Nitric oxide (NO) inhibits the VSM enzyme, whereas it is stimulatory in macrophages, neurons, pancreatic cells, and sea urchin eggs (52). Recently, it has been shown that oxidative stress increases [Ca2+]i in fresh bovine coronary VSM cells through a pathway that involves cADPR (55) and that NO inhibits ADPR cyclase in coronary artery VSM (52).
Only one study investigated the effect of ANG II on the activity of ADP-ribosyl cyclase (27). This laboratory found that in membrane preparations of neonatal but not older cardiac myocytes, ANG II increased cyclase activity in a dose-dependent fashion (27). The mechanism by which ANG II stimulated an increase in ADPR cyclase activity is unknown, but these investigators speculated that a G protein-coupled process is involved (27). Because of the crucial importance of afferent arterioles in regulating glomerular filtration and sodium balance, we investigated the effects of ANG II on Ca2+ signaling in freshly isolated afferent arterioles using inhibitors of IP3R, RyR, and ADPR cyclase.
METHODS
All studies were performed in compliance with the guidelines and practices of the University of North Carolina at Chapel Hill Institutional Animal Care and Use Committee.
Preparation of fresh afferent arterioles. We used the magnetized polystyrene microsphere sieving technique as previously described in our laboratory (20) to isolate afferent arterioles (<20-μm diameter) from 5- to 6-wk-old Sprague-Dawley rats maintained in the Chapel Hill Colony. Phosphate-buffered saline (PBS), with the following composition (in mM) 137 NaCl, 4.1 KCl, 0.66 KH2PO4, 3.4 Na2HPO4, 2.5 NaHCO3, 1.0 MgCl2, and 5 glucose, was adjusted daily to pH 7.4 at 4°, 23°, and 34°C. The vessel segments in PBS containing 0.1% BSA were treated with collagenase type IV (Worthington, 197 U/mg, 510 μg/ml) for 18 min at 34°C. Arterioles were loaded with fura 2-AM (2 μM) and 0.1% BSA for 45 min at 23°C in the dark. After the arterioles were washed twice with PBS, the suspension was kept on ice. Ca2+ (1.1 mM) was added shortly before analysis of an arteriole. For studies of arterioles in Ca2+-free buffer, the vessels were kept in buffer containing 107 M Ca2+ only during the fura incubation and then they were washed with Ca2+-free buffer before analysis.
Vessels were stimulated with ANG II (3 x 107 M) (18). The concentrations of antagonists we chose were based on published results: 8-(N,N-diethylamino) octyl 3,4,5-trimethoxybenzoate (TMB-8) (44, 47), 2-aminoethoxydiphenyl borate (2-APB) (41, 42), ryanodine (7, 18), Zn2+ (13), and nicotinamide (46). A dose-response analysis was performed for 8-Br cADPR (51). Arterioles were incubated with inhibitors for at least 1 min before initiation of an experimental measurement.
Measurement of [Ca2+]i. We measured [Ca2+]i as previously described (20). Afferent arterioles were identified by their morphology and measured diameter of 1520 μm. Additionally, we required visualization of microspheres in the lumen to exclude the possibility that the vessel was an efferent arteriole. The microspheres (4.04.5 μm) do not pass beyond the glomerular capillaries. An arteriole was centered in a small window of the optical field that was free of glomeruli or tubular fragments.
Although endothelial cells are present in these nonperfused afferent arterioles, we and others assumed that VSM cells provide the major source of fura-2 fluorescence owing to the greater bulk of VSM cells compared with endothelial cells (9). Studies in deendothelialized renal microvessels showed that ANG II-induced Ca2+ increases were not different from those of control arterioles (43). Furthermore, all reagents were added to the bath and therefore there was no immediate intraluminal exposure of endothelial cells to agonists and antagonists. We showed previously that freshly isolated single preglomerular VSM cells and afferent arterioles respond similarly, both qualitatively and quantitatively, to endothelin (20).
The VSM cells were excited alternately with light of 340- and 380-nm wavelength from a dual-excitation wavelength Delta-Scan equipped with dual monochronometers and a chopper [Photon Technology International (PTI)] as previously described (1719). After passing signals through a barrier filter (510 nm), fluorescence was detected by a photomultiplier tube. Signal intensity was acquired, stored, and processed by an IBM-compatible Pentium computer and Felix software (PTI). Background subtraction was performed in all studies. There was no interruption in the recording during the addition of reagents to the chamber. A video camera projected images of afferent arterioles onto a video monitor permitting visualization of contraction of vessel segments.
Reagents. We purchased ANG II, 2-APB, TMB-8, 8-Br cADPR, and nicotinamide from Sigma (St. Louis, MO), collagenase type IV from Worthington (Lakewood, NJ), fura-2AM from Molecular Probes (Eugene, OR), and magnetized microspheres from Spherotech (Libertyville, IL).
Statistics. Data are presented as means ± SE. Each data set was derived from afferent arterioles originating from at least three separate experimental days, two rats (4 kidneys) per experiment. Individual arterioles were studied only once and then discarded. In experiments with inhibitors, values for ANG II peak responses were included only for the experimental days in which a particular inhibitor was employed. Paired data for arterioles before and after ANG II stimulation were tested with Student's paired t-test. Unpaired t-tests were employed for comparisons of responses between groups.
RESULTS
[Ca2+]i response to ANG II. Afferent arterioles in Ca2+-containing PBS responded to ANG II with a sharp peak response in 13 s. The mean baseline [Ca2+]i was 64 ± 4, the peak 189 ± 10, and the plateau 100 ± 7 nM (n = 48, P < 0.01 for both peak and plateau values vs. baseline; Fig. 1). Thus the net peak increase in [Ca2+]i after ANG II stimulation for all control experiments was 125 ± 10 nM.
Effect of inhibitors of the IP3R. To assess the contribution of G protein-coupled ANG II receptor stimulation of phospholipase C (PLC), formation of IP3, and IP3R-mediated release of [Ca2+]i from the SR, we employed two inhibitors of the IP3R, TMB-8 and 2-APB (42, 47). Because these studies were conducted in Ca2+-containing buffer, inhibition of IP3R-mediated Ca2+ mobilization may also affect Ca2+ entry mechanisms (e.g., voltage-gated Ca2+ and store-operated Ca2+ entry channels) as well. Approximately one-half to two-thirds of the initial peak Ca2+ responses to ANG II in afferent arterioles have been shown to arise from mobilization mechanisms (5, current study, vide infra). Afferent arterioles were stimulated with ANG II in the absence (n = 11) or presence (n = 8) of TMB-8 (105 M; P < 0.01 for ANG II ± TMB-8 vs. baseline). A representative tracing (Fig. 2A) shows that the peak response to ANG II was attenuated by TMB-8-mediated inhibition of the IP3R. Group averages (Fig. 2C) demonstrate that the net ANG II-stimulated increase in [Ca2+]i with TMB-8 present was 40 ± 4 nM and with ANG II alone 152 ± 18 nM in this group of experiments (74% inhibition, P < 0.01). In a similar fashion, afferent arterioles were pretreated with 2-APB (33 μM) to antagonize IP3R (Fig. 2B). In this group of experiments, ANG II alone increased [Ca2+]i by 180 ± 18 nM (n = 11) and in the presence of 2-APB (n = 13) by 35 ± 4 nM (81% inhibition, P < 0.01 for ANG II + 2-APB vs. baseline, and <0.01 for ANG II alone vs. ANG II + 2-APB; Fig. 2C). Neither TMB-8 nor 2-APB had any influence on baseline [Ca2+]i values (P > 0.5 for both agents). These data confirm that ANG II-stimulated IP3 production and activation of the IP3R-mediated Ca2+ release from the SR contribute substantially to the initial Ca2+ response.
Effect of inhibitors of the RyR. We postulated that blockade of RyRs should abolish CICR (4) and the ability of cADPR to enhance the Ca2+ sensitivity of RyRs (24, 36). Ryanodine in high concentrations locks the RyR in a closed state (7, 48). Previously, we showed that a low concentration of ryanodine (23 μM) activates the RyR to mobilize Ca2+ from the SR (18). In contrast, a high concentration of ryanodine (100 μM) had no effect on baseline [Ca2+]i (21). In the current study, we found that ryanodine (100 μM) did not alter basal [Ca2+]i in afferent arterioles but inhibited the subsequent ANG II response by 69%. As Fig. 3C shows, the average increase in [Ca2+]i following stimulation with ANG II alone was 163 ± 27 nM (n = 12) and with ANG II following ryanodine was 50 ± 10 nM (n = 8, P < 0.01).
We tested the ability of 8-Br cADPR, a cell-permeant antagonist of the RyR (36), to attenuate the Ca2+ response to ANG II. In a dose-response analysis, 8-Br cADPR at concentrations of 50 and 100 μM was equally inhibitory (ANG II-induced increases in [Ca2+]i were 38 ± 5 and 31 ± 5 nM, respectively, P < 0.05 vs. baseline) but were twice as potent as a concentration of 10 μM (ANG II response 62 ± 7 nM). Therefore, we pooled the data for the two higher concentrations. 8-Br cADPR did not alter baseline values of [Ca2+]i (P > 0.3). A representative tracing is shown in Fig. 3B. In this group of experiments, ANG II alone increased [Ca2+]i by 152 ± 17 nM (n = 11), but in the presence of 8-Br cADPR, the net increase was only 36 ± 5 nM (76% inhibition, n = 16, P < 0.01 for ANG II alone vs. ANG II + 8-Br cADPR; Fig. 3C). Together, these two inhibitors of RyRs demonstrate the importance of cADPR in conjunction with RyRs for amplifying the [Ca2+]i signal initiated by IP3. That 8-Br cADPR blocks the ANG II-induced Ca2+ increase suggests that ANG II is linked to the production of cADPR.
Inhibitors of the ADPR cyclase. Thus a major question in trying to understand the relationship between agonist stimulation of a G protein-coupled receptor to initiate the sequence of IP3 generation, activation of the IP3R, release of Ca2+ from the SR, and participation of the RyR to augment the Ca2+ signal is what is the communication to the membrane ADPR cyclase to direct formation of cADPR We tested the effect of nicotinamide and Zn2+, well-studied inhibitors of the ADPR cyclase of VSM (13, 46), on Ca2+ signaling in response to ANG II. Nicotinamide (3 mM) pretreatment of afferent arterioles did not change baseline values of [Ca2+]i but reduced the [Ca2+]i response to ANG II by 66% (Fig. 4A). In this group of experiments, ANG II alone increased [Ca2+]i by 102 ± 18 nM (n = 7); in the presence of nicotinamide, the response was reduced to 35 ± 6 nM (n = 9, P < 0.01; Fig. 4C).
As noted above, Zn2+ inhibits the VSM ADPR cyclase, whereas it stimulates the cyclase of nonvascular cells (13). Because Zn2+ may inhibit voltage-gated Ca2+ entry channels (32) and because voltage-gated Ca2+ entry is a major entry pathway in afferent arterioles (6, 10, 29), our studies assessing the action of Zn2+ on the ADPR cyclase were done in Ca2+-free buffer. A typical tracing (Fig. 4B) shows that the response to ANG II is attenuated in Ca2+-free PBS and is markedly inhibited by Zn2+ (3 mM). In nominally Ca2+-free PBS, ANG II increased [Ca2+]i by 77 ± 30 nM (a value that is 62% of the response of afferent arterioles to ANG II in Ca2+-replete PBS). In the presence of Zn2+, the response to ANG II was decreased to 25 ± 10 nM (n = 7 for both, P < 0.05 for Zn2+ + ANG II vs. baseline and <0.03 for ANG II vs. ANG II + Zn2+; Fig. 4C). Zn2+ had no effect on baseline [Ca2+]i. Taken together, the nicotinamide and Zn2+ data suggest that there is a pathway used by ANG II that increases the activity of the ADPR cyclase and that is independent of the IP3 pathway.
Simultaneous inhibition of ADPR cyclase and of IP3R. To further document the relative contributions of activation of the IP3R and of formation of cAPPR, which sensitizes the RyR to Ca2+, we employed inhibitors of both of these pathways. In this group of experiments, ANG II increased [Ca2+]i by 100 ± 13 nM (n = 16). In afferent arterioles pretreated with nicotinamide and 2-APB, the increase in [Ca2+]i following addition of ANG II was 18 ± 4 nM and with nicotinamide and TMB-8 17 ± 3 nM (n = 9 and 8, respectively, P < 0.01 vs. ANG II alone and P < 0.01 for ANG II + inhibitor vs. baseline; Fig. 5).
DISCUSSION
In the present study, we show that G protein-coupled receptor activation by ANG II leads to Ca2+ release from the SR via two different receptor/release channels, one sensitive to IP3 and the other to ryanodine. We present new information that ANG II signaling in fresh afferent arterioles causes activation of the VSM ADPR cyclase and formation of cADPR. The mechanism by which this occurs awaits elucidation. Only one study, performed in neonatal rat cardiac myocytes, suggests that ANG II (possibly with involvement of a G protein) activates an ADPR cyclase to form cADPR, which, in turn, stimulates the RyR to release Ca2+ from the SR (27).
We were the first to demonstrate that fresh preglomerular VSM cells have a functional RyR (18) and that depletion of SR Ca2+ stores with ryanodine activates store-operated Ca2+ entry in both Wistar-Kyoto and spontaneously hypertensive rats (18, 19). Subsequently, other laboratories presented evidence for a role for a RyR in renal VSM. Stimulation of cultured renal VSM cells with RGD peptides induces Ca2+ waves that are completely blocked by closure of the RyR with ryanodine (20 μM) but not by the IP3R antagonist xestospongin (8). In the isolated hydronephrotic kidney model, ANG II-induced arteriolar oscillations in afferent arterioles are blocked by ryanodine but not by 2-APB, an IP3R inhibitor (50). In freshly dispersed VSM cells derived from third and fourth order renal vessels, the IP3R and RyR-sensitive Ca2+ stores of the SR appear to communicate with each other, in contrast to the spatial organization of pulmonary arterial VSM cells in which the compartments are independent (30). Taken together, these studies confirm the important physiological role of RyRs in renal VSM.
In the present study, we examined ANG II-stimulated participation of cADPR by inhibiting the ADPR cyclase and by assessing the contribution of cADPR to the stimulation of RyRs. When RyR is locked in a nonconductive state with a high concentration of ryanodine (100 μM) (7, 48), the [Ca2+]i response of afferent arterioles to ANG II is markedly reduced. Pretreatment of arterioles with the cell-permeant antagonist of cADPR, 8-Br cADPR, likewise substantially diminishes the response to ANG II. Thus ANG II appears to be involved in stimulating the formation of cADPR. Taken together, our data are consistent with the conclusion that the effect of cADPR on the RyR and the participation of cADPR in sensitizing the RyR to Ca2+ (CICR) are major components of the total [Ca2+]i response to ANG II stimulation of afferent arteriolar VSM and suggest that Ca2+ release from the SR through the IP3R accounts for less than one-third of the mobilization pathway.
To examine the possibility that ANG II influences the activity of the ADPR cyclase, we used two inhibitors of this plasmalemmal membrane enzyme, nicotinamide (46) and Zn2+ (13). Nicotinamide does not actually inhibit the cyclase but rather forces the reaction in the reverse direction to form NAD+ rather than cADPR (33). Nicotinamide is not known to influence other components of ANG II signaling pathways. Because Zn2+ may inhibit voltage-gated Ca2+ entry (32), a major entry channel in afferent arterioles (6, 10, 29), the Zn2+ experiments were performed in Ca2+-free buffer. Zn2+ may also inhibit the membrane Ca2+ ATPases (28). If this were a significant effect in renal VSM cells, one would expect an enhancement of the [Ca2+]i response to ANG II rather than inhibition. Zn2+ is also an inhibitor of proton currents generated via NOX in phagocytic cells (11). Whether Zn2+ has an interaction with the novel isoforms of NOX of VSM (2) has not been studied. Superoxide dismutase, which converts superoxide to H2O2, is inhibited by Zn2+ (15), an effect that would enhance rather than diminish a possible role for superoxide in ANG II signaling. The strong inhibitory effects of nicotinamide and Zn2+ in our studies provide evidence that ANG II stimulation of VSM of afferent arterioles ultimately results in activation of the ADPR cyclase to form cADPR.
An enzyme capable of forming cADPR was first described in homogenates of sea urchin eggs (38) and subsequently has been shown to be present in a wide variety of cell types (24, 25, 35). In mammals, a single bifunctional protein, CD38, can act as a cyclase or hydrolase for cADPR (37, 45). The ADPR cyclase of VSM appears to have several unique characteristics that distinguish it from CD38 (13). Of particular interest is the fact that the VSM enzyme is inhibited, rather than stimulated, by Zn2+ (13).
Mammalian ADPR cyclases of specific cell types are stimulated by a number of different agonists: for example, estrogen in myometrium (1), glucose in pancreatic beta cells (49), retinoic acid and triiodothyronine in aortic VSM cells (12), reactive oxygen species in bovine coronary VSM (55), ANG II in neonatal cardiac myocytes (27), tumor necrosis factor- and interleukin-1 in glomerular mesangial cell (54), and acetylcholine and endothelin in airway smooth muscle (51). How this structurally diverse group of molecules mediates the same process, namely activation of the ADPR cyclase, has not yet been elucidated with certainty.
In summary, we show that ANG II stimulation of afferent arterioles increases [Ca2+]i via several distinct pathways. The classic G protein-coupled receptor activation that results in IP3 generation and release of [Ca2+]i from the SR likely provides an initial and transient burst of [Ca2+]i, which can activate CICR from RyR. We present new information demonstrating that the ANG II response is blocked by the specific cADPR antagonist, 8-Br cADPR, and by high concentrations of ryanodine, which closes RyR. At present, we do not know the pathway(s) that link activation of the ADPR cyclase to ANG II stimulation of afferent arteriolar VSM, studies of which await further investigation.
GRANTS
This work was supported in part by a grant from the Thomas H. Maren Foundation and from National Heart, Lung, and Blood Institute Grant HL-02334.
FOOTNOTES
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
REFERENCES
Barata H, Thompson M, Zielinska W, Han YS, Mantilla CB, Prakash YS, Feitoza S, Sieck G, and Chini EN. The role of cyclic-ADP-ribose-signaling pathway in oxytocin-induced Ca2+ transients in human myometrium cells. Endocrinology 145: 881889, 2004.
Bengtsson SH, Gulluyan LM, Dusting GJ, and Drummond GR. Novel isoforms of NADPH oxidase in vascular physiology and pathophysiology. Clin Exp Pharmacol Physiol 30: 849854, 2003.
Berridge MJ. Inositol trisphosphate and calcium signalling. Nature 361: 315325, 1993.
Berridge MJ. The endoplasmic reticulum: a multifunctional signaling organelle. Cell Calcium 32: 235249, 2002.
Carmines PK, Fowler BC, and Bell PD. Segmentally distinct effects of depolarization on intracellular [Ca2+] in renal arterioles. Am J Physiol Renal Fluid Electrolyte Physiol 265: F677F685, 1993.
Carmines PK and Navar LG. Disparate effects of Ca channel blockade on afferent and efferent arteriolar responses to ANG II. Am J Physiol Renal Fluid Electrolyte Physiol 256: F1015F1020, 1989.
Carroll S, Skarmeta JG, Yu X, Collins KD, and Inesi G. Interdependence of ryanodine binding, oligomeric receptor interactions, and Ca2+ release regulation in junctional sarcoplasmic reticulum. Arch Biochem Biophys 290: 239247, 1991.
Chan WL, Holstein-Rathlou NH, and Yip KP. Integrin mobilizes intracellular Ca2+ in renal vascular smooth muscle cells. Am J Physiol Cell Physiol 280: C593C603, 2001.
Che Q and Carmines PK. Angiotensin II triggers EGFR tyrosine kinase-dependent Ca2+ influx in afferent arterioles. Hypertension 40: 700706, 2002.
Conger JD and Falk SA. KCl and angiotensin responses in isolated rat renal arterioles: effects of diltiazem and low-calcium medium. Am J Physiol Renal Fluid Electrolyte Physiol 264: F134F140, 1993.
DeCoursey TE, Morgan D, and Cherny VV. The voltage dependence of NADPH oxidase reveals why phagocytes need proton channels. Nature 422: 531534, 2003.
De Toledo FG, Cheng J, and Dousa TP. Retinoic acid and triiodothyronine stimulate ADP-ribosyl cyclase activity in rat vascular smooth muscle cells. Biochem Biophys Res Commun 238: 847850, 1997.
De Toledo FG, Cheng J, Liang M, Chini EN, and Dousa TP. ADP-ribosyl cyclase in rat vascular smooth muscle cells: properties and regulation. Circ Res 86: 11531159, 2000.
Dousa TP, Chini EN, and Beers KW. Adenine nucleotide diphosphates: emerging second messengers acting via intracellular Ca2+ release. Am J Physiol Cell Physiol 271: C1007C1024, 1996.
Endroczi E, Hepp J, Sasvary M, Walentin S, and Levay G. Dipeptidyl peptidase IV (DP IV) and superoxide dismutase activity in thymus-derived lymphocytes: effects of inhibitory peptides and Zn2+ in vitro. Acta Physiol Hung 75: 3544, 1990.
Evans AM and Dipp M. Hypoxic pulmonary vasoconstriction: cyclic adenosine diphosphate-ribose, smooth muscle Ca2+ stores and the endothelium. Respir Physiol Neurobiol 132: 315, 2002.
Fellner SK and Arendshorst WJ. Capacitative calcium entry in smooth muscle cells from preglomerular vessels. Am J Physiol Renal Physiol 277: F533F542, 1999.
Fellner SK and Arendshorst WJ. Ryanodine receptor and capacitative Ca2+ entry in fresh preglomerular vascular smooth muscle cells. Kidney Int 58: 16861694, 2000.
Fellner SK and Arendshorst WJ. Store-operated Ca2+ entry is exaggerated in fresh preglomerular vascular smooth muscle cells of SHR. Kidney Int 61: 21322141, 2002.
Fellner S and Arendshorst WJ. Endothelin A and B receptors of preglomerular vascular smooth muscle. Kidney Int 65: 18101817, 2004.
Fellner SK and Parker LA. Endothelin B receptor Ca2+ signaling in shark vascular smooth muscle: participation of inositol trisphosphate and ryanodine receptors. J Exp Biol 207: 34113417, 2004.
Galione A and Churchill GC. Interactions between calcium release pathways: multiple messengers and multiple stores. Cell Calcium 32: 343354, 2002.
Galione A, Lee HC, and Busa WB. Ca2+-induced Ca2+ release in sea urchin egg homogenates: modulation by cyclic ADP-ribose. Science 253: 11431146, 1991.
Guse AH. Cyclic ADP-ribose: a novel Ca2+-mobilising second messenger. Cell Signal 11: 309316, 1999.
Guse AH. Regulation of calcium signaling by the second messenger cyclic adenosine diphosphoribose (cADPR). Curr Mol Med 4: 239248, 2004.
Guse AH, da Silva CP, Berg I, Skapenko AL, Weber K, Heyer P, Hohenegger M, Ashamu GA, Schulze-Koops H, Potter BV, and Mayr GW. Regulation of calcium signalling in T lymphocytes by the second messenger cyclic ADP-ribose. Nature 398: 7073, 1999.
Higashida H, Zhang J, Hashii M, Shintaku M, Higashida C, and Takeda Y. Angiotensin II stimulates cyclic ADP-ribose formation in neonatal rat cardiac myocytes. Biochem J 352: 197202, 2000.
Hogstrand C, Verbost PM, Bonga SE, and Wood CM. Mechanisms of zinc uptake in gills of freshwater rainbow trout: interplay with calcium transport. Am J Physiol Regul Integr Comp Physiol 270: R1141R1147, 1996.
Inscho EW, Mason MJ, Schroeder AC, Deichmann PC, Stiegler KD, and Imig JD. Agonist-induced calcium regulation in freshly isolated renal microvascular smooth muscle cells. J Am Soc Nephrol 8: 569579, 1997.
Janiak R, Wilson SM, Montague S, and Hume JR. Heterogeneity of calcium stores and elementary release events in canine pulmonary arterial smooth muscle cells. Am J Physiol Cell Physiol 280: C22C33, 2001.
Kannan MS, Fenton AM, Prakash YS, and Sieck GC. Cyclic ADP-ribose stimulates sarcoplasmic reticulum calcium release in porcine coronary artery smooth muscle. Am J Physiol Heart Circ Physiol 270: H801H806, 1996.
Kerchner GA, Canzoniero LM, Yu SP, Ling C, and Choi DW. Zn2+ current is mediated by voltage-gated Ca2+ channels and enhanced by extracellular acidity in mouse cortical neurones. J Physiol 528: 3952, 2000.
Kim H, Jacobson EL, and Jacobson MK. Synthesis and degradation of cyclic ADP-ribose by NAD glycohydrolases. Science 261: 13301333, 1993.
Lee HC. Potentiation of calcium- and caffeine-induced calcium release by cyclic ADP-ribose. J Biol Chem 268: 293299, 1993.
Lee HC. Mechanisms of calcium signaling by cyclic ADP-ribose and NAADP. Physiol Rev 77: 11331164, 1997.
Lee HC. Physiological functions of cyclic ADP-ribose and NAADP as calcium messengers. Annu Rev Pharmacol Toxicol 41: 317345, 2001.
Lee HC, Graeff RM, and Walseth TF. ADP-ribosyl cyclase and CD38. Multifunctional enzymes in Ca2+ signaling. Adv Exp Med Biol 419: 411419, 1997.
Lee HC, Walseth TF, Bratt GT, Hayes RN, and Clapper DL. Structural determination of a cyclic metabolite of NAD+ with intracellular Ca2+-mobilizing activity. J Biol Chem 264: 16081615, 1989.
Li N, Teggatz EG, Li PL, Allaire R, and Zou AP. Formation and actions of cyclic ADP-ribose in renal microvessels. Microvasc Res 60: 149159, 2000.
Li PL, Tang WX, Valdivia HH, Zou AP, and Campbell WB. cADP-ribose activates reconstituted ryanodine receptors from coronary arterial smooth muscle. Am J Physiol Heart Circ Physiol 280: H208H215, 2001.
Missiaen L, Callewaert G, De Smedt H, and Parys JB. 2-Aminoethoxydiphenyl borate affects the inositol 1,4,5-trisphosphate receptor, the intracellular Ca2+ pump and the nonspecific Ca2+ leak from the non-mitochondrial Ca2+ stores in permeabilized A7r5 cells. Cell Calcium 29: 111116, 2001.
Peppiatt CM, Collins TJ, Mackenzie L, Conway SJ, Holmes AB, Bootman MD, Berridge MJ, Seo JT, and Roderick HL. 2-Aminoethoxydiphenyl borate (2-APB) antagonises inositol 1,4,5-trisphosphate-induced calcium release, inhibits calcium pumps and has a use-dependent and slowly reversible action on store-operated calcium entry channels. Cell Calcium 34: 97108, 2003.
Praddaude F, Marchetti J, Alhenc-Gelas F, and Ader J. Dissimilar mechanisms of Ca2+ response to bradykinin in different types of juxtamedullary glomerular arterioles. Am J Physiol Renal Physiol 277: F697F705, 1999.
Salomonsson M and Arendshorst WJ. Norepinephrine-induced calcium signaling pathways in afferent arterioles of genetically hypertensive rats. Am J Physiol Renal Physiol 281: F264F272, 2001.
Schuber F and Lund FE. Structure and enzymology of ADP-ribosyl cyclases: conserved enzymes that produce multiple calcium mobilizing metabolites. Curr Mol Med 4: 249261, 2004.
Sethi JK, Empson RM, and Galione A. Nicotinamide inhibits cyclic ADP-ribose-mediated calcium signalling in sea urchin eggs. Biochem J 319: 613617, 1996.
Smallridge RC, Gist ID, and Ambroz C. 8-Diethylamino-octyl-3,4,5-trimethoxybenzoate, a calcium store blocker, increases calcium influx, inhibits alpha-1 adrenergic receptor calcium mobilization, and alters iodide transport in FRTL-5 rat thyroid cells. Endocrinology 129: 542549, 1991.
Sutko JL, Airey JA, Welch W, and Ruest L. The pharmacology of ryanodine and related compounds. Pharmacol Rev 49: 5398, 1997.
Takasawa S, Tohgo A, Noguchi N, Koguma T, Nata K, Sugimoto T, Yonekura H, and Okamoto H. Synthesis and hydrolysis of cyclic ADP-ribose by human leukocyte antigen CD38 and inhibition of the hydrolysis by ATP. J Biol Chem 268: 2605226054, 1993.
Takenaka T, Ohno Y, Hayashi K, Saruta T, and Suzuki H. Governance of arteriolar oscillation by ryanodine receptors. Am J Physiol Regul Integr Comp Physiol 285: R125R131, 2003.
White TA, Kannan MS, and Walseth TF. Intracellular calcium signaling through the cADPR pathway is agonist specific in porcine airway smooth muscle. FASEB J 17: 482484, 2003.
Yu JZ, Zhang DX, Zou AP, Campbell WB, and Li PL. Nitric oxide inhibits Ca2+ mobilization through cADP-ribose signaling in coronary arterial smooth muscle cells. Am J Physiol Heart Circ Physiol 279: H873H881, 2000.
Yusufi AN, Cheng J, Thompson MA, Burnett JC, and Grande JP. Differential mechanisms of Ca2+ release from vascular smooth muscle cell microsomes. Exp Biol Med (Maywood) 227: 3644, 2002.
Yusufi AN, Cheng J, Thompson MA, Dousa TP, Warner GM, Walker HJ, and Grande JP. cADP-ribose/ryanodine channel/Ca2+ release signal transduction pathway in mesangial cells. Am J Physiol Renal Physiol 281: F91F102, 2001.
Zhang AY, Yi F, Teggatz EG, Zou AP, and Li PL. Enhanced production and action of cyclic ADP-ribose during oxidative stress in small bovine coronary arterial smooth muscle. Microvasc Res 67: 159167, 2004.