Faculty Collaboration Database

Cyclic ADP-ribose contributes to contraction and Ca2+ release by M1 muscarinic receptor activation in coronary arterial smooth muscle. J Vasc Res 2003;40(1):28-36

Date

03/20/2003

Pubmed ID

12644723

DOI

10.1159/000068936

Scopus ID

2-s2.0-0037227424 (requires institutional sign-in at Scopus site)   48 Citations

Abstract

The present study determined the role of cyclic ADP-ribose (cADPR) in mediating vasoconstriction and Ca(2+) 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 micromol/L) and oxotremorine (OXO; 2.5-80 micromol/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 Ca(2+) ([Ca(2+)](i)) was determined by fluorescence spectrometry using fura-2 as a fluorescence indicator. OXO produced a rapid increase in [Ca(2+)](i) in freshly isolated single coronary arterial smooth muscle cells (CASMCs) bathed with Ca(2+)-free Hanks' solution. This OXO-induced rise in [Ca(2+)](i) was significantly reduced by pirenzepine (PIR; an M(1) 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 beta-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 Ca(2+) release induced by activation of M(1) muscarinic receptors.

Author List

Ge ZD, Zhang DX, Chen YF, Yi FX, Zou AP, Campbell WB, Li PL

Authors

William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
David X. Zhang MD, PhD Associate Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

ADP-ribosyl Cyclase
Acetylcholine
Animals
Calcium
Calcium Channels
Cattle
Coronary Vessels
Cyclic ADP-Ribose
Endothelium, Vascular
Enzyme Inhibitors
Fluorescent Dyes
Fura-2
Inositol 1,4,5-Trisphosphate Receptors
Muscarinic Agonists
Muscle Contraction
Muscle, Smooth, Vascular
Niacinamide
Oxotremorine
Receptor, Muscarinic M1
Receptors, Cytoplasmic and Nuclear
Receptors, Muscarinic
Ryanodine
Ryanodine Receptor Calcium Release Channel
Spectrometry, Fluorescence
Vasoconstriction
Vasodilator Agents