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

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T1 - Endothelial P2Y receptors induce hyperpolarisation of vascular smooth muscle by release of endothelium-derived hyperpolarising factor

AU - Malmsjö, Malin

AU - Erlinge, David

AU - Högestätt, Edward

AU - Zygmunt, Peter

PY - 1999

Y1 - 1999

N2 - The effects of P2Y receptor agonists on smooth muscle membrane potential in isolated ring segments of rat mesenteric artery were examined by intracellular microelectrodes. In the presence of inhibitors of nitric oxide-synthase and cyclo-oxygenase, the selective P2Y1 receptor agonist adenosine 5'-O-thiodiphosphate (ADPbetaS) induced endothelium-dependent membrane hyperpolarisations, which were abolished by a combination of the K+ channel inhibitors charybdotoxin and apamin, providing direct evidence that ADPbetaS releases endothelium-derived hyperpolarising factor (EDHF). 2-MethylthioATP and ATP, each which stimulates both endothelial P2Y receptors and P2X receptors on the smooth muscle cells, also elicited hyperpolarisation, but only after desensitisation of P2X receptors with alphabeta-methylATP indicating that simultaneous activation of P2X receptors may counteract the action of EDHF. In conclusion, activation of endothelial P2Y receptors induce release of EDHF.

AB - The effects of P2Y receptor agonists on smooth muscle membrane potential in isolated ring segments of rat mesenteric artery were examined by intracellular microelectrodes. In the presence of inhibitors of nitric oxide-synthase and cyclo-oxygenase, the selective P2Y1 receptor agonist adenosine 5'-O-thiodiphosphate (ADPbetaS) induced endothelium-dependent membrane hyperpolarisations, which were abolished by a combination of the K+ channel inhibitors charybdotoxin and apamin, providing direct evidence that ADPbetaS releases endothelium-derived hyperpolarising factor (EDHF). 2-MethylthioATP and ATP, each which stimulates both endothelial P2Y receptors and P2X receptors on the smooth muscle cells, also elicited hyperpolarisation, but only after desensitisation of P2X receptors with alphabeta-methylATP indicating that simultaneous activation of P2X receptors may counteract the action of EDHF. In conclusion, activation of endothelial P2Y receptors induce release of EDHF.

KW - Membrane potential

KW - K+ channel

KW - Purinoceptor

KW - Vascular endothelium

U2 - 10.1016/S0014-2999(98)00848-6

DO - 10.1016/S0014-2999(98)00848-6

M3 - Article

VL - 364

SP - 169

EP - 173

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 1879-0712

IS - 2-3

ER -