Modulation of aortic and cardiac G protein alpha subunits and their mRNAs during norepinephrine infusion in rats.
These studies examine the possibility that alterations in the expression of G protein alpha subunits occur during desensitization of adrenergic responses in the cardiovascular system. To desensitize adrenergic receptors, rats were infused with norepinephrine (NE) subcutaneously (0.1 mg/kg/h) for 3 or 6 days using osmotic minipumps. G protein alpha subunits and their mRNAs were then measured in the aorta and heart using selective antibodies and cDNA probes. Infusion of NE for 6 days significantly decreases the levels of Gs alpha, Gi alpha and Go alpha in the aorta. The mRNAs for the alpha subunits are not altered in the aorta after NE infusion for 3 or 6 days indicating that reduced mRNA expression does not account for the decreased proteins. In the atrium and ventricle the levels of Gs alpha decrease after NE infusion for 3 days but then return to control levels by day 6. The levels of atrial and ventricular Gi alpha are unaltered after NE infusion for 3 days but increase significantly by day 6. Go alpha levels do not change in the atrium or ventricle on either day. The level of Gi2 alpha mRNA increases after NE infusion for 6 days and may account for the increased alpha i protein. The levels of the other G alpha mRNAs do not change in the atrium or ventricle. These results demonstrate that expression of G protein alpha subunits is altered during cardiovascular desensitization, raising the possibility that modulation of the alpha subunits may contribute to reduced adrenergic responsiveness.
Zhou
Y
Y
Department of Pharmacology, Medical College of Pennsylvania, Philadelphia 19129.
Friedman
E
E
Roberts
J
J
Johnson
M D
MD
D000818:Animals; D001011:Aorta / Q000378:metabolism*; D015152:Blotting, Northern; D015153:Blotting, Western; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D007279:Injections, Subcutaneous; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D012333:RNA, Messenger; D019204:GTP-Binding Proteins; D009638:Norepinephrine