Nitric oxide activates skeletal and cardiac ryanodine receptors

Long-term depression (LTD) of synaptic transmission can be induced by several mechanisms, one thought to involve Ca2+-dependent activation of postsynaptic nitric oxide (NO) synthase and subsequent diffusion of NO to the presynaptic terminal. We used the stable NO donor S-nitroso- N-acetylpenicillamine (SNAP) to study the NO-dependent form of LTD at Schaffer collateral-CA1 synapses in vitro. SNAP (100 μM) enhanced the induction of LTD via a cascade that was blocked by the N-methyl-d-aspartate receptor antagonist d-2-amino-5-phosphonopentanoic acid (50 μM), NO guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (10 μM), and the PKG inhibitor KT5823 (1 μM). We further show that LTD induced by low-frequency stimulation in the absence of SNAP also is blocked by KT5823 or Rp-8-(4-chlorophenylthio)-guanosine 3′,5′-cyclic monophosphorothioate (10 μM), cyclic guanosine 3′,5′ monophosphate-dependent protein kinase (PKG) inhibitors with different mechanisms of action. Furthermore SNAP-facilitated LTD was blocked when release from intracellular calcium stores was inhibited by ryanodine (10 μM). Finally, two cell-permeant antagonists of the cyclic ADP-ribose binding site on ryanodine receptors also were able to block the induction of LTD. These results support a cascade for induction of homosynaptic, NO-dependent LTD involving activation of guanylyl cyclase, production of guanosine 3′,5′ cyclic monophosphate and subsequent PKG activation. This process has an additional requirement for release of Ca2+ from ryanodine-sensitive stores, perhaps dependent on the second-messenger cyclic ADP ribose.

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Nitric oxide inhibits calcium release from sarcoplasmic reticulum of porcine tracheal smooth muscle cells

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1997.272.1.l1 ◽

1997 ◽

Vol 272 (1) ◽

pp. L1-L7 ◽

Cited By ~ 14

Author(s):

M. S. Kannan ◽

Y. S. Prakash ◽

D. E. Johnson ◽

G. C. Sieck

Keyword(s):

Nitric Oxide ◽

Smooth Muscle ◽

Sarcoplasmic Reticulum ◽

Calcium Release ◽

Ryanodine Receptors ◽

Tracheal Smooth Muscle ◽

Nitric Oxide Donor ◽

Ip3 Receptors ◽

Video Fluorescence Microscopy ◽

Inositol 1,4,5 Trisphosphate

In the present study, effects of the nitric oxide donor, S-nitroso-N-acetylpenicillamine (SNAP), on sarcoplasmic reticulum (SR) Ca2+ release were examined in freshly dissociated porcine tracheal smooth muscle (TSM) cells. Fura 2-loaded TSM cells were imaged using video fluorescence microscopy. SR Ca2+ release was induced by acetylcholine (ACh), which acts principally through inositol 1,4,5-trisphosphate (IP3) receptors, and by caffeine, which acts principally through ryanodine receptors (RyR). SNAP inhibited ACh-induced SR Ca2+ release at both 0 and 2.5 mM extracellular Ca2+. Degraded SNAP had no effect on ACh-induced SR Ca2+ release. SNAP also inhibited caffeine-induced SR Ca2+ release. ACh-induced Ca2+ influx was not affected by SNAP when SR reloading was blocked by thapsigargin. SNAP also did not affect SR Ca2+ reuptake. The membrane-permeant analogue of guanosine 3',5'-cyclic monophosphate (cGMP), 8-bromo-cGMP, mimicked the effects of SNAP. These results suggest that, in porcine TSM cells, SNAP reduces the intracellular Ca2+ response to ACh and caffeine by inhibiting SR Ca2+ release through both IP3 and RyR, but not by inhibiting influx or repletion of the SR Ca2+ stores. These effects are likely mediated via cGMP-dependent mechanisms.

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Involvement of Nitric Oxide in Iodine Deficiency-Induced Microvascular Remodeling in the Thyroid Gland: Role of Nitric Oxide Synthase 3 and Ryanodine Receptors

Endocrinology ◽

10.1210/en.2014-1729 ◽

2014 ◽

Vol 156 (2) ◽

pp. 707-720 ◽

Cited By ~ 13

Author(s):

J. Craps ◽

C. Wilvers ◽

V. Joris ◽

B. De Jongh ◽

J. Vanderstraeten ◽

...

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Thyroid Gland ◽

Mrna Expression ◽

Iodine Deficiency ◽

Ryanodine Receptors ◽

No Production

Iodine deficiency (ID) induces microvascular changes in the thyroid gland via a TSH-independent reactive oxygen species-hypoxia inducible factor (HIF)-1α-vascular endothelial growth factor (VEGF) pathway. The involvement of nitric oxide (NO) in this pathway and the role of calcium (Ca2+) and of ryanodine receptors (RYRs) in NO synthase 3 (NOS3) activation were investigated in a murine model of goitrogenesis and in 3 in vitro models of ID, including primary cultures of human thyrocytes. ID activated NOS3 and the production of NO in thyrocytes in vitro and increased the thyroid blood flow in vivo. Using bevacizumab (a blocking antibody against VEGF-A) in mice, it appeared that NOS3 is activated upstream of VEGF-A. L-nitroarginine methyl ester (a NOS inhibitor) blocked the ID-induced increase in thyroid blood flow in vivo and NO production in vitro, as well as ID-induced VEGF-A mRNA and HIF-1α expression in vitro, whereas S-nitroso-acetyl-penicillamine (a NO donor) did the opposite. Ca2+ is involved in this pathway as intracellular Ca2+ flux increased after ID, and thapsigargin activated NOS3 and increased VEGF-A mRNA expression. Two of the 3 known mammalian RYR isoforms (RYR1 and RYR2) were shown to be expressed in thyrocytes. RYR inhibition using ryanodine at 10μM decreased ID-induced NOS3 activation, HIF-1α, and VEGF-A expression, whereas RYR activation with ryanodine at 1nM increased NOS3 activation and VEGF-A mRNA expression. In conclusion, during the early phase of TSH-independent ID-induced microvascular activation, ID sequentially activates RYRs and NOS3, thereby supporting ID-induced activation of the NO/HIF-1α/VEGF-A pathway in thyrocytes.

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Molecular Interaction Between Nitric Oxide and Ryanodine Receptors of Skeletal and Cardiac Sarcoplasmic Reticulum

Antioxidants and Redox Signaling ◽

10.1089/ars.2000.2.1-5 ◽

2000 ◽

Vol 2 (1) ◽

pp. 5-16 ◽

Cited By ~ 39

Author(s):

Guy Salama ◽

Elizaveta V. Menshikova ◽

Jonathan J. Abramson

Keyword(s):

Nitric Oxide ◽

Sarcoplasmic Reticulum ◽

Molecular Interaction ◽

Ryanodine Receptors ◽

Cardiac Sarcoplasmic Reticulum

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Cyclic ADP ribose-mediated Ca2+ signaling in mediating endothelial nitric oxide production in bovine coronary arteries

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00441.2005 ◽

2006 ◽

Vol 290 (3) ◽

pp. H1172-H1181 ◽

Cited By ~ 23

Author(s):

Guo Zhang ◽

Eric G. Teggatz ◽

Andrew Y. Zhang ◽

Matthew J. Koeberl ◽

Fan Yi ◽

...

Keyword(s):

Nitric Oxide ◽

Coronary Arteries ◽

Ryanodine Receptors ◽

No Production ◽

Signaling Mechanism ◽

Adp Ribosyl Cyclase ◽

Cyclic Adp Ribose ◽

Intracellular Ca ◽

A Cell ◽

Endothelial Nitric Oxide

The present study tested the hypothesis that cyclic ADP ribose (cADPR) serves as a novel second messenger to mediate intracellular Ca2+ mobilization in coronary arterial endothelial cells (CAECs) and thereby contributes to endothelium-dependent vasodilation. In isolated and perfused small bovine coronary arteries, bradykinin (BK)-induced concentration-dependent vasodilation was significantly attenuated by 8-bromo-cADPR (a cell-permeable cADPR antagonist), ryanodine (an antagonist of ryanodine receptors), or nicotinamide (an ADP-ribosyl cyclase inhibitor). By in situ simultaneously fluorescent monitoring, Ca2+ transient and nitric oxide (NO) levels in the intact coronary arterial endothelium preparation, 8-bromo-cADPR (30 μM), ryanodine (50 μM), and nicotinamide (6 mM) substantially attenuated BK (1 μM)-induced increase in intracellular [Ca2+] by 78%, 80%, and 74%, respectively, whereas these compounds significantly blocked BK-induced NO increase by about 80%, and inositol 1,4,5-trisphosphate receptor blockade with 2-aminethoxydiphenyl borate (50 μM) only blunted BK-induced Ca2+-NO signaling by about 30%. With the use of cADPR-cycling assay, it was found that inhibition of ADP-ribosyl cyclase by nicotinamide substantially blocked BK-induced intracellular cADPR production. Furthermore, HPLC analysis showed that the conversion rate of β-nicotinamide guanine dinucleotide into cyclic GDP ribose dramatically increased by stimulation with BK, which was blockable by nicotinamide. However, U-73122, a phospholipase C inhibitor, had no effect on this BK-induced increase in ADP-ribosyl cyclase activity for cADPR production. In conclusion, these results suggest that cADPR importantly contributes to BK- and A-23187-induced NO production and vasodilator response in coronary arteries through its Ca2+ signaling mechanism in CAECs.

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