Cyclic ADP-ribose contributes to contraction and Ca2+ release by M1 muscarinic receptor activation in coronary arterial smooth muscle

Zhi-Dong Ge, David X. Zhang, Ya Fei Chen, Fu Xian Yi, Ai Ping Zou, William B. Campbell, Pin Lan Li*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

The 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; 2.5-80 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.

Original languageEnglish (US)
Pages (from-to)28-36
Number of pages9
JournalJournal of Vascular Research
Volume40
Issue number1
DOIs
StatePublished - 2003

Keywords

  • Calcium
  • Coronary artery
  • Cyclic adenosine diphosphate-ribose
  • Muscarinic receptors
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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