Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of clonidine and yohimbine on plasma cyclic nucleotide levels were investigated in both clonidine-naive and clonidine-treated male mice. Clonidine increased plasma cyclic GMP but decreased slightly cyclic AMP levels in clonidine-naive mice. Clonidine treatment for 10-14 days in the drinking water did not decrease the cyclic GMP response to clonidine indicating that no tolerance develops to the effect of clonidine on plasma cyclic GMP. alpha 2-Agonists, such as clonidine, oxymetazoline and naphazoline, were more potent than phenylephrine, an alpha 1-agonist, in increasing cyclic GMP, although azepexole, a weak alpha 2-agonist, had no effect. Inhibition of clonidine-induced increase in plasma cyclic GMP by yohimbine, hexamethonium and atropine, but not by prazosin suggests that the effect of clonidine is mediated by the central alpha 2-adrenoceptors, activating the muscarinic receptor-linked guanylate cyclase through the stimulation of vagal activity. Yohimbine increased plasma cyclic AMP levels in clonidine-naive mice. Inhibition of this effect by hexamethonium and propranolol suggests that yohimbine increases plasma cyclic AMP through increasing the sympathetic tone. The increase in plasma cyclic AMP elicited by yohimbine was potentiated by chronic clonidine treatment. Enhancement of the cyclic AMP effect of yohimbine found in clonidine-treated mice may be regarded as a precipitated withdrawal symptom and indicate development of dependence on clonidine.
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PMID:Effects of clonidine and yohimbine on plasma cyclic nucleotide levels in clonidine-naive and clonidine-treated mice. 301 8

The inhibitory effects of endothelium-derived relaxing factor (EDRF) on the contractions induced by norepinephrine and clonidine in rat aorta were examined. Carbachol induced a relaxation of norepinephrine-induced contraction in rat aorta with endothelium. Removal of endothelium inhibited the carbachol-induced relaxation and increased the magnitude of norepinephrine-induced contraction. Quinacrine, a phospholipase A2 inhibitor, methylene blue, a guanylate cyclase inhibitor and tetraethylammonium, a potassium permeability inhibitor, inhibited carbachol-induced relaxation and augmented the magnitude of norepinephrine-induced contraction only when endothelium was present. Clonidine induced a contraction when endothelium was removed or muscle was treated with methylene blue. The contractions induced by norepinephrine and clonidine were equally sensitive to prazosin and equally less sensitive to yohimbine. Clonidine inhibited the norepinephrine-induced contraction, whereas it potentiated the angiotensin 11- or 12 mM K-induced contractions in the aorta with endothelium. The inhibitory effect of clonidine on the norepinephrine-induced contraction was reduced by endothelium-removal and by methylene blue but not by yohimbine. These results suggest that norepinephrine has a strong direct stimulating action and clonidine has a weak one on vascular smooth muscle cells possibly mediated by alpha 1-adrenoceptors, and their contractile effects are inhibited by the spontaneously released EDRF.
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PMID:Role of endothelium in the contractions induced by norepinephrine and clonidine in rat aorta. 387 8

The mechanism underlying the analgesic effect of clonidine, an alpha(2)-adrenoceptor agonist, remains uncertain. Activation of alpha(2)-adrenoceptor induces the release of nitric oxide (NO) from endothelial cells, which has led us to test the hypothesis that the observed antinociceptive effect induced by the systemic administration of clonidine depends on the NO-cGMP pathway. The possible involvement of an opioid link in the antinociceptive effect of clonidine was also evaluated. The antinociceptive effect induced by systemic administration (intravenous or intraperitoneal) of clonidine was evaluated using the rat paw formalin, mice tail-flick and writhing tests. Clonidine (3-120 microg/kg) induces a dose-dependent antinociceptive effect in the formalin, tail-flick and writhing tests. The antinociceptive effect of clonidine in a dose that had no sedative effect assessed by rota rod test, was significantly reduced by NO-synthase and guanylyl cyclase inhibition. The antinociceptive effect of morphine, but not clonidine, was inhibited by naloxone. Our current results suggest that the antinociceptive effect of systemic clonidine does not involve the opioid receptor and is modulated by the NO-cGMP pathway.
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PMID:Role of the NO-cGMP pathway in the systemic antinociceptive effect of clonidine in rats and mice. 1521 64