Reduced G protein function in desensitized rat aorta.
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-GTP gamma S binding to G protein alpha subunits in aortic membranes. The alpha 1 adrenergic agonist phenylephrine stimulated GTP tau S binding to Gs and Gi in aortic membranes and the degree of stimulation was reduced in desensitized vessels. 5-HT stimulated binding to Gi and Go 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 alpha 1 receptors to activate Gs and Gi.
Johnson
M D
MD
Department of Pharmacology, Medical College of Pennsylvania, Philadelphia.
Wang
H Y
HY
Ciechanowski
D
D
Friedman
E
E
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D012969:Sodium Fluoride / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D011942:Receptors, Adrenergic, alpha; D012969:Sodium Fluoride; D019204:GTP-Binding Proteins; D009638:Norepinephrine