Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Redox modulation of Gi protein expression and adenylyl cyclase signaling: role of nitric oxide. 1502 40

Dilation of rat preglomerular microvessels (PGMV) by activation of adenosine A2A receptors (A2AR) is coupled to epoxyeicosatrienoic acid (EET) release. We have investigated the commonality of this signal transduction pathway, i.e., sequential inhibition of G(salpha), adenylyl cyclase, PKA, and Ca2+-activated K+ (KCa) channel activity, to the vasoactive responses to A2AR activation by a selective A2A agonist, CGS-21680, compared with those of 11,12-EET. Male Sprague-Dawley rats were anesthetized, and microdissected arcuate arteries (110-130 microm) were cannulated and pressurized to 80 mmHg. Vessels were superfused with Krebs solution containing NG-nitro-L-arginine methyl ester (L-NAME) and indomethacin and preconstricted with phenylephrine. We assessed the effect of 3-aminobenzamide (10 microM), an inhibitor of mono-ADP-ribosyltranferases, on responses to 11,12-EET (3 nM) and CGS-21680 (10 microM) and found that both were inhibited by approximately 70% (P<0.05), whereas the response to SNP (10 microM) was unaffected. Furthermore, 11,12-EET (100 nM), like cholera toxin (100 ng/ml), stimulated ADP-ribose formation in homogenates of arcuate arteries compared with control. SQ-22536 (10 microM), an inhibitor of adenylyl cyclase activity, and myristolated PKI (14-22) amide (5 microM), an inhibitor of PKA, decreased activity of 11,12-EET and CGS-21680. Incubation of 11,12-EET (3 nM-3 microM) with PGMV resulted in an increase in cAMP levels (P<0.05). The responses to both 11,12-EET and CGS-21680 were significantly reduced by superfusion of iberiotoxin (100 nM), an inhibitor of KCa channel activity. Thus in rat PGMV activation of A2AR is coupled to EET release upstream of adenylyl cyclase activation and EETs stimulate mono-ADP-ribosyltransferase, resulting in Gsalpha protein activation.
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PMID:Adenosine2A receptor vasodilation of rat preglomerular microvessels is mediated by EETs that activate the cAMP/PKA pathway. 1647 79

Angiotensin II converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) presumably stimulate renin secretion by interrupting angiotensin II feedback inhibition. The increase in cytosolic calcium caused by activation of Gq-coupled AT1 receptors may mediate the renin-inhibitory effect of angiotensin II at the cellular level, implying that ACEI and ARB may work by reducing intracellular calcium. Here, we investigated whether angiotensin II blockade acts predominantly through Gs-mediated stimulation of adenylyl cyclase (AC) by testing the effect of ACEI and ARB in mice with juxtaglomerular cell-specific deficiency of the AC-stimulatory Gsalpha. The ACEI captopril and quinaprilate and the ARB candesartan significantly increased plasma renin concentration (PRC) to 20 to 40 times basal PRC in wild-type mice but did not significantly alter PRC in Gsalpha-deficient mice. Captopril also completely abrogated renin stimulation in wild-type mice after co-administration of propranolol, indomethacin, and L-NAME. Treatment with enalapril and a low-NaCl diet for 7 days led to a 35-fold increase in PRC among wild-type mice but no significant change in PRC among Gsalpha-deficient mice. Three different pharmacologic inhibitors of AC reduced the stimulatory effect of captopril by 70% to 80%. In conclusion, blockade of angiotensin II stimulates renin synthesis and release indirectly through the action of ligands that activate the cAMP/PKA pathway in a Gsalpha-dependent fashion, including catecholamines, prostaglandins, and nitric oxide.
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PMID:Stimulation of renin secretion by angiotensin II blockade is Gsalpha-dependent. 2039 78