Insulin-like growth factor inhibits vascular contraction to 5-hydroxytryptamine: Involvement of tyrosine phosphatase

This study tests the hypothesis that insulin-like growth factor 1 (IGF-1)-i nduced vasodilation is due to the stimulation of tyrosine phosphatase. Rat aortic segments (endothelium intact) were placed in muscle baths for force measurement. Segments were contracted to serotonin [5-hydroxytyptamine (5-H T), 10(-7)10(-5) M] before and after incubation with IGF-1 (10-100 nM; 90 m in). IGF-1 caused a 20% inhibition of 5-HT-induced contractions. This inhib ition was reversed by the tyrosine phosphatase inhibitors sodium orthovanad ate and molybdate, Orthovanadate did not alter inhibitory properties of the calcium channel antagonist verapamil, suggesting that the phosphatase inhi bitors were relatively specific. IGF-1-induced inhibition was not altered b y blockade of nitric oxide synthase. Western blot analysis confirmed that t he 5-HT-induced stimulation of tyrosine phosphorylation of the 42-kDa extra cellular signal-regulated mitogen-activated protein kinase protein was redu ced by IGF-1 (52% inhibition), an inhibition that was attenuated by orthova nadate. These data are consistent with the hypothesis that the vasodilator activity of IGF-1 is mediated by the activation of a tyrosine phosphatase. (C) 2000 Elsevier Science Inc. All rights reserved.