Activation of adenosine A(2A) but not A(2B) receptors is involved in uridine adenosine tetraphosphate-induced porcine coronary smooth muscle relaxation

Sun, Changyan; Jiao, Tong; Merkus, Daphne; Duncker, Dirk J.; Mustafa, S. Jamal und Zhou, Zhichao (2019): Activation of adenosine A(2A) but not A(2B) receptors is involved in uridine adenosine tetraphosphate-induced porcine coronary smooth muscle relaxation. In: Journal of Pharmacological Sciences, Vol. 141, No. 1: pp. 64-69

Abstract

Activation of both adenosine A(2A) and A(2B) receptors (A(2B)R) contributes to coronary vasodilation. We previously demonstrated that uridine adenosine tetraphosphate (Up(4)A) is a novel vasodilator in the porcine coronary microcirculation, acting mainly on A(2A)R in smooth muscle cells (SMC). We further investigated whether activation of A(2B)R is involved in Up(4)A-mediated coronary SMC relaxation. Both A(2A)R and A(2B)R may stimulate H2O2 production leading to activation of K(ATP )channels in SMCs, we also studied the involvement of H2O2 and K-ATP channels in Up(4)A-mediated effect. Coronary small arteries dissected from the apex of porcine hearts were mounted on wire myograph for Up(4)A concentration responses. Up(4)A-induced coronary SMC relaxation was attenuated by A(2A)R but not A(2B)R antagonism or non-selective P2R antagonism, despite greater endogenous A(2B)R expression vs. A(2A)R in both coronary small arteries and primary cultured coronary SMCs. Moreover, Up(4)A-induced coronary SMC relaxation was blunted by H2O2 catabolism. This effect was not altered by K-ATP channel blockade. Combination of H2O2 catabolism and A(2A)R antagonism attenuated Up4A-induced coronary SMC relaxation to the similar extent as A(2A)R antagonism alone. Collectively, Up(4)A-induced porcine coronary SMC relaxation is mediated by activation of A(2A)R-H2O2 pathway. This process does not involve A(2B)R, P2R or K-ATP channels. (C) 2019 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.

• Item Type: Journal article
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 1347-8613
• Language: English