Abstract
Stimulation of vascular beta-adrenoceptors causes vasodilatation through activation of adenylyl cyclase (AC) and plasma membrane potassium channels, and beta-adrenoceptors have been linked to activation of extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase in various cell lines. However, how these findings relate to functional responses in intact tissues is largely unknown. The aim of this study, therefore, was to investigate the role of ERK in beta-adrenoceptor-induced vasodilatation. Segments of porcine coronary artery were mounted in a Mulvany wire myograph and bathed in Krebs-Henseleit buffer gassed with 95% O(2)/5% CO(2) and maintained at 37 degrees C. Tissues were pre-contracted with the thromboxane mimetic U46619, endothelin-1 or KCl. Cumulative concentration-response curves to beta-adrenoceptor agonists or forskolin were then carried out in the absence or presence of the mitogen-activated protein kinase kinase (MEK) inhibitors PD98059 (10 or 50 microM) or U0126 (10 microM). PD98059 caused a concentration-dependent leftward shift in response to isoprenaline (pEC(50) control, 7.5 +/- 0.1; 50 microM PD98059, 8.1 +/- 0.1: P < 0.05). Inhibition of MEK also enhanced the maximum relaxation seen with s...Continue Reading
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Citations
Apr 29, 2014·Vascular Pharmacology·Miguel Perez-AsoM Dolores Ivorra
Sep 27, 2014·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·P S WongR E Roberts
Jul 17, 2012·European Journal of Pharmacology·Chukwuemeka O UhiaraRichard E Roberts
Nov 19, 2011·European Journal of Pharmacology·Alice LelliottRichard E Roberts
Nov 21, 2019·European Journal of Pharmacology·Taseer AhmadRichard Roberts
Jul 31, 2020·European Journal of Pharmacology·Taseer AhmadRichard Roberts