Endothelial P2Y receptors induce hyperpolarisation of vascular smooth muscle by release of endothelium-derived hyperpolarising factor

The effects of P2Y receptor agonists on smooth muscle membrane potential in isolated ring segments of rat mesenteric artery were examined by intracell ular microelectrodes. In the presence of inhibitors of nitric oxide-synthas e and cyclo-oxygenase, the selective P2Y(1) receptor agonist adenosine 5'-O -thiodiphosphate (ADP beta S) induced endothelium-dependent membrane hyperp olarisations, which were abolished by a combination of the K+ channel inhib itors charybdotoxin and apamin, providing direct evidence that ADP beta S r eleases endothelium-derived hyperpolarising factor (EDHF). 2-MethylthioATP and ATP, each which stimulates both endothelial P2Y receptors and P2X recep tors on the smooth muscle cells, also elicited hyperpolarisation, but only after desensitisation of P2X receptors with alpha,beta-methylATP indicating that simultaneous activation of P2X receptors may counteract the action of EDHF. In conclusion, activation of endothelial P2Y receptors induce releas e of EDHF. (C) 1999 Elsevier Science B.V. All rights reserved.