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- Title
Cyclic ADP-Ribose Contributes to Contraction and Ca<sup>2+</sup> Release by M<sub>1</sub> Muscarinic Receptor Activation in Coronary Arterial Smooth Muscle.
- Authors
Z.-D. Ge; D.X. Zhang; Y.-F. Chen; F.-X. Yi; A.-P. Zou; W.B. Campbell; P.-L. Li
- Abstract
AbstractThe present study determined the role of cyclic ADP-ribose (cADPR) in mediating vasoconstriction and Ca2+ release in response to the activation of muscarinic receptors. Endothelium-denuded small bovine coronary arteries were microperfused under transmural pressure of 60 mm Hg. Both acetylcholine (ACh; 1 nmol/L to 1 μmol/L) and oxotremorine (OXO; 2.580 μmol/L) produced a concentration-dependent contraction. The vasoconstrictor responses to both ACh and OXO were significantly attenuated by nicotinamide (Nicot; an ADP-ribosyl cyclase inhibitor), 8-bromo-cADPR (8-Br-cADPR; a cADPR antagonist) or ryanodine (Ry; an Ry receptor antagonist). Intracellular Ca2+ ([Ca2+]i) was determined by fluorescence spectrometry using fura-2 as a fluorescence indicator. OXO produced a rapid increase in [Ca2+]i in freshly isolated single coronary arterial smooth muscle cells (CASMCs) bathed with Ca2+-free Hanks solution. This OXO-induced rise in [Ca2+]i was significantly reduced by pirenzepine (PIR; an M1 receptor-specific blocker), Nicot, 8-Br-cADPR or Ry. The effects of OXO on the activity of ADP-ribosyl cyclase (cADPR synthase) were examined in cultured CASMCs by measuring the rate of cyclic GDP- ribose (cGDPR) formation from β-nicotinamide guanine dinucleotide. It was found that OXO produced a concentration-dependent increase in the production of cGDPR. The stimulatory effect of OXO on ADP-ribosyl cyclase was inhibited by both PIR and Nicot. These results suggest that the cADPR signaling pathway participates in the contraction of small coronary arterial smooth muscle and Ca2+ release induced by activation of M1 muscarinic receptors.Copyright © 2003 S. Karger AG, Basel
- Subjects
ADENOSINE diphosphate; MUSCARINIC receptors; ENDOTHELIUM; CORONARY arteries; SMOOTH muscle
- Publication
Journal of Vascular Research, 2003, Vol 40, Issue 1, p28
- ISSN
1018-1172
- Publication type
Article