PMID: 8968381Dec 1, 1996Paper

Serotonin activates the mitogen-activated protein kinase pathway in vascular smooth muscle: use of the mitogen-activated protein kinase kinase inhibitor PD098059

The Journal of Pharmacology and Experimental Therapeutics
S W Watts

Abstract

Serotonin (5-hydroxytryptamine, 5-HT) promotes changes in vascular smooth muscle contractility and is a vascular smooth muscle mitogen. The hypothesis that 5-HT-induced arterial contraction is partially dependent on tyrosine kinase activation was tested in this study. Specifically, we examined the role of the tyrosine kinase mitogen-activated protein kinase kinase in 5-HT-induced vascular contraction by using a novel inhibitor of mitogen-activated protein kinase kinase PD098059. Helical strips of rat aorta, mesenteric and tail artery denuded of endothelium were mounted in tissue baths for measurement of isometric contractile force. 5-HT-induced contraction in all arteries was mediated by 5-HT2A receptors as ketanserin (3-30 nM) was a competitive antagonist in all arteries (pKB = 8.58-8.96). Genistein (5 x 10(-6) M) and tyrphostinB42 (3 x 10(-5) M), two unrelated tyrosine kinase inhibitors, shifted 5-HT-induced contraction toward the right in all arteries (approximately eight-fold). By contrast, daidzein (5 x 10(-6) M), the inactive isomer of genistein, did not reduce contraction to 5-HT in any artery. These findings suggest that 5-HT-induced activation of tyrosine kinase(s) may be a signal transduction pathway used by vascular ...Continue Reading

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