Reduced G protein function in desensitized rat aorta

M. D. Johnson, H. Y. Wang, D. Ciechanowski, E. Friedman

Research output: Contribution to journalArticlepeer-review

Abstract

These studies investigated the role of G proteins in vascular desensitization. Rats were infused with norepinephrine (NE) subcutaneously (0.1 mg/kg/hr) for 6 days using osmotic minipumps and aortas were obtained. NE-stimulated contraction was blunted in aortas obtained from NE infused rats compared to aortas from vehicle infused controls. Contractile responses to KCl and serotonin (5-HT) were not affected by NE infusion indicating desensitization was specific to certain receptors. Dose response curves for NaF-stimulated contraction were right-shifted in aortas from NE infused rats suggesting reduced G protein function in these vessels. G protein function was studied further by assessing G protein activation in response to receptor stimulation. This was done by measuring agonist-stimulated increases in 35S-GTPγS binding to G protein alpha subunits in aortic membranes. The alpha1 adrenergic agonist phenylephrine stimulated GTPτS binding to G(s) and G(i) in aortic membranes and the degree of stimulation was reduced in desensitized vessels. 5-HT stimulated binding to G(i) and G(o) in aortic membranes and the response was not altered in desensitized vessels. Thus, vascular desensitization produced by NE infusion involves selective reductions in the ability of alpha1 receptors to activate G(s) and G(i).

Original languageEnglish
Pages (from-to)255-259
Number of pages5
JournalJournal of Pharmacology and Experimental Therapeutics
Volume259
Issue number1
StatePublished - 1991
Externally publishedYes

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