Platelets from spontaneously hypertensive rats exhibit decreased expression of inhibitory guanine nucleotide regulatory protein. Relation with adenylyl cyclase activity.
We have recently demonstrated an enhanced expression of inhibitory guanine nucleotide regulatory protein (Gi) in the heart and aorta from spontaneously hypertensive rats (SHR) as compared with control Wistar-Kyoto (WKY) rats; this enhanced Gi expression was associated with an increased inhibition of adenylyl cyclase by inhibitory hormones and decreased stimulation of adenylyl cyclase by stimulatory hormones. In the present studies, we have determined the levels of stimulatory and inhibitory guanine nucleotide regulatory proteins (Gs and Gi, respectively) in platelets from SHR by cholera toxin- and pertussis toxin-catalyzed ADP-ribosylations, respectively, as well as by immunoblotting techniques using specific antibodies for Gs and Gi. Cholera toxin catalyzed the ADP-ribosylation of a single protein of M(r) 45,000 in rat platelets from SHR and WKY rats, and the labeling of this band was not altered in SHR as compared with WKY rats. Pertussis toxin, on the other hand, catalyzed the ADP-ribosylation of a single protein band of M(r) 41,000 in platelets from SHR and WKY rats, and unlike the response in heart and aorta, the labeling of this band was significantly decreased in SHR as compared with WKY rats. Furthermore, immunoblotting experiments using AS/7 antibody, which is specific for Gi alpha-1 and Gi alpha-2, showed a decrease in Gi alpha-2 in platelets from SHR as compared with WKY rats. In addition, the inhibitory effects of angiotensin II and atrial natriuretic factor on adenylyl cyclase and cAMP levels were completely abolished in SHR platelets, whereas the stimulatory effects of GTP, N-ethylcarboxamide adenosine, prostaglandin E1, and forskolin on adenylyl cyclase and cAMP levels were enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)
Anand-Srivastava
M B
MB
Department of Physiology, Faculty of Medicine, University of Montreal, Quebec, Canada.
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000262:Adenylyl Cyclases / Q000097:blood*; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood; D019204:GTP-Binding Proteins / Q000032:analysis*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR / Q000097:blood*; D011921:Rats, Inbred WKY
D005576:Colforsin; D019830:Adenosine-5'-(N-ethylcarboxamide); D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D000527:Alprostadil; D000241:Adenosine