Role of tyrosine kinase on Ca2+ entry and refilling of agonist-sensitive Ca2+ stores in vascular smooth muscles.

Abstract:

:Recent evidence suggests that some Ca2+ channels are regulated by a tyrosine kinase pathway. The possibility that Ca2+ entry is regulated by tyrosine kinase was investigated in canine vascular muscles. Functional studies were carried out in the dog mesenteric arteries and saphenous veins. Nicardipine-insensitive refilling of phenylephrine-sensitive Ca2+ stores of endothelium-denuded dog mesenteric artery, previously depleted of Ca2+, measured after a 30-min exposure of the arterial rings to Ca2+ in the absence and presence of genistein (10-100 microM), tyrphostin 23 (10-100 microM), tyrphostin 47 (10-100 microM), SK&F 96365 (3-30 microM), or vehicle, DMSO, as phenylephrine contraction in Ca(2+)-free medium, decreased with increasing concentrations of the inhibitors compared with DMSO-treated and control. Phenylephrine contraction in Ca(2+)-free medium was not affected in a consistent manner by tyrosine kinase inhibitors when added after the store refilling period, in Ca(2+)-free medium, 5 min prior to stimulation with phenylephrine, indicating that the inhibitors have no effect on the Ca2+ release mechanism or that they act directly on myofilaments. Cyclopiazonic acid (30 microM), an inhibitor of the sarcoplasmic reticulum Ca2+ pump, caused transient contractions in the dog saphenous vein only in the presence of extracellular Ca2+. These transient contractions were inhibited by tyrphostin 23 (30-100 microM), tyrphostin 47 (30-100 microM), genistein (30-100 microM), and SK&F 96365 (50-100 microM) but not by the vehicle DMSO. The results from this study provided evidence that a tyrosine kinase pathway is involved in the regulation of Ca2+ entry since inhibitors of tyrosine kinase are able to attenuate presumed Ca2+ entry following agonist-mediated Ca2+ store depletion. This route of Ca2+ entry is also sensitive to blockade by SK&F 96365.

authors

Low AM

subject

Has Abstract

pub_date

1996-03-01 00:00:00

pages

298-304

issue

3

eissn

0008-4212

issn

1205-7541

journal_volume

74

pub_type

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