Redox modulation of Gi protein expression and adenylyl cyclase signaling: role of nitric oxide.
Nitric oxide (NO) has been shown to regulate a variety of physiological functions, including vascular tone. The inhibition of NO synthase by N(omega)-nitro-L-arginine methyl ester (L-NAME) has been reported to increase arterial blood pressure. The present studies were undertaken to investigate if the increased blood pressure by L-NAME is associated with enhanced expression of Gi proteins, implicated in the pathogenesis of hypertension. L-NAME was administered orally into Sprague-Dawley rats for a period of 4 weeks. Control rats were given plain tap water only. The systolic blood pressure was enhanced in L-NAME-treated rats as compared with control rats; however, the heart-to-body weight ratio was not different in the two groups. The levels of Gialpha-2 and Gialpha-3 proteins and their mRNA as determined by western and northern blotting, respectively, were significantly augmented in hearts from L-NAME-treated rats, whereas the levels of Gsalpha and Gbeta were unaltered. In addition, the effect of low concentrations of GTPgammaS on forskolin-stimulated adenylyl cyclase activity (receptor-independent functions of Gialpha) was significantly enhanced, whereas the receptor-dependent inhibitions of adenylyl cyclase were completely attenuated in L-NAME-treated rats. Whereas cholera toxin-mediated stimulation of adenylyl cyclase was unaltered in both group of rats, the stimulatory effects of some agonists on adenylyl cyclase activity were diminished in L-NAME-treated rats. These results suggest the implication of NO in the modulation of Gi protein expression and associated adenylyl cyclase signaling.
Anand-Srivastava
Madhu B
MB
Department of Physiology, and Groupe de recherche sur le système nerveux autonome (GRSNA), Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada. anandsrm@physio.umontreal.ca
Di Fusco
Francesco
F
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics / Q000378:metabolism*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D008297:Male; D018721:Muscarinic Agonists / Q000378:metabolism; D009206:Myocardium / Q000737:chemistry; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D010095:Oxotremorine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014020:Tissue Extracts / Q000737:chemistry / Q000378:metabolism
D004791:Enzyme Inhibitors; D018721:Muscarinic Agonists; D014020:Tissue Extracts; D000804:Angiotensin II; D005576:Colforsin; D009569:Nitric Oxide; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D010095:Oxotremorine; D002772:Cholera Toxin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs; D000262:Adenylyl Cyclases; D019331:NG-Nitroarginine Methyl Ester