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

Gen Pharmacol. 2000 Feb;34(2):137-45. doi: 10.1016/s0306-3623(00)00055-0.

Abstract

This study tests the hypothesis that insulin-like growth factor 1 (IGF-1)-induced 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-HT), 10(-7)-10(-5) M] before and after incubation with IGF-1 (10-100 nM; 90 min). IGF-1 caused a 20% inhibition of 5-HT-induced contractions. This inhibition was reversed by the tyrosine phosphatase inhibitors sodium orthovanadate and molybdate. Orthovanadate did not alter inhibitory properties of the calcium channel antagonist verapamil, suggesting that the phosphatase inhibitors were relatively specific. IGF-1-induced inhibition was not altered by blockade of nitric oxide synthase. Western blot analysis confirmed that the 5-HT-induced stimulation of tyrosine phosphorylation of the 42-kDa extracellular signal-regulated mitogen-activated protein kinase protein was reduced by IGF-1 (52% inhibition), an inhibition that was attenuated by orthovanadate. These data are consistent with the hypothesis that the vasodilator activity of IGF-1 is mediated by the activation of a tyrosine phosphatase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / enzymology
  • Aorta, Thoracic / physiology
  • Drug Synergism
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiology
  • Enzyme Inhibitors / pharmacology
  • In Vitro Techniques
  • Insulin-Like Growth Factor I / pharmacology*
  • Male
  • Mitogen-Activated Protein Kinases / metabolism
  • Molybdenum / pharmacology
  • Muscle Contraction / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / enzymology
  • Muscle, Smooth, Vascular / physiology
  • Nitric Oxide / physiology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitroarginine / pharmacology
  • Phosphorylation / drug effects
  • Protein Tyrosine Phosphatases / antagonists & inhibitors
  • Protein Tyrosine Phosphatases / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / pharmacology*
  • Serotonin Antagonists / pharmacology*
  • Vanadates / pharmacology
  • Vasoconstriction / drug effects*
  • Vasoconstriction / physiology
  • Vasodilator Agents / pharmacology*

Substances

  • Enzyme Inhibitors
  • Serotonin Antagonists
  • Vasodilator Agents
  • molybdate
  • Nitroarginine
  • Nitric Oxide
  • Serotonin
  • Vanadates
  • Insulin-Like Growth Factor I
  • Molybdenum
  • Nitric Oxide Synthase
  • Mitogen-Activated Protein Kinases
  • Protein Tyrosine Phosphatases