Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. In incubated tubule fragments from renal cortex of fed rats gluconeogenesis from pyruvate was stimulated by adrenaline (1mum optimum) and by the selective alpha-adrenergic agonists oxymetazoline and amidephrine. The selective beta-agonists isoproterenol and salbutamol were ineffective at concentrations up to 10mum. 2. Stimulation of gluconeogenesis by 1mum-adrenaline was almost completely blocked by 10mum-phentolamine (alpha-antagonist), partially blocked by 10mum-phenoxybenzamine (alpha-antagonist) and unaffected by 10mum-propranolol (beta-antagonist). 3. Adrenaline stimulation of gluconeogenesis was rapid and was sustained for at least 1h. 4. Oxymetazoline (alpha-agonist) was extremely potent in stimulation of gluconeogenesis. This compound stimulated glucose production from pyruvate, lactate and glutamate, but not from succinate or glycerol. 5. In the absence of Ca(2+) oxymetazoline was ineffective, whereas some stimulatory effect of adrenaline on gluconeogenesis was still observed. 6. Glucagon had no effect on gluconeogenesis from pyruvate in the presence of 1.27mm-Ca(2+) and inhibited the process in the presence of 0.25mm-Ca(2+). Parathyrin (parathyroid hormone) stimulated gluconeogenesis at 1.27mm-Ca(2+). 7. In short incubations of tubule fragments glucagon, papaverine and adrenaline significantly increased 3':5'-cyclic AMP. Adrenaline also slightly decreased 3':5'-cyclic GMP. Oxymetazoline had no effect on the amount of either cyclic nucleotide. 8. At all concentrations tested, theophylline and papaverine decreased gluconeogenesis from pyruvate. 9. It is concluded that renal gluconeogenesis may be increased by alpha- but not beta-adrenergic stimuli and that this is probably independent of changes in 3':5'-cyclic AMP or 3':5'-cyclic GMP. An involvement of Ca(2+) in the action of oxymetazoline appears likely, but this is less certain with adrenaline.
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PMID:Hormonal control of gluconeogenesis in tubule fragments from renal cortex of fed rats. Effects of alpha-adrenergic stimuli, glucagon, theophylline and papaverine. 59 61

This study was designed to investigate the interaction between the NO/L-arginine pathway and the alpha2-adrenoceptor-mediated endothelium-dependent vasorelaxation. Reactivity of isolated resistance mesenteric arterial segments from mice lacking the gene for constitutive endothelial NO synthase (eNOS- mice, n=14) and from their wild-type controls (WT mice, n=46) was studied in isometric conditions in the presence of indomethacin (blocker of cyclooxygenase). Oxymetazoline (OXY, 0.01 to 30 micromol/L; a selective alpha2-adrenoceptor agonist) induced an endothelium-dependent relaxation of eNOS- but not WT arteries preconstricted either with phenylephrine or serotonin. In the presence of Nomega-nitro-L-arginine (l-NNA, 100 micromol/L), an inhibitor of NOS, OXY induced an endothelium-dependent relaxation of WT mesenteric arteries. l-NNA had no effect on the relaxation caused by OXY in eNOS- arterial rings. Therefore, the relaxation caused by OXY was independent of NO formation. To demonstrate the inhibitory role of NO on the alpha2-adrenoceptor-mediated relaxation, subthreshold (0.1 nmol/L) to threshold (1 nmol/L) concentrations of sodium nitroprusside (donor of NO) were added to l-NNA-treated arteries before OXY challenges: in these conditions, the alpha2-adrenoceptor-mediated relaxation of eNOS- and WT arteries was inhibited. OXY-induced relaxation was restored on readdition of methylene blue (1 micromol/L, inhibitor of guanylate cyclase), suggesting that cGMP may be the mechanism of inhibition of the alpha2-adrenergic pathway in the presence of NO. Finally, OXY-mediated relaxation was blocked by tetraethylammonium (1 mmol/L) but not glibenclamide (1 micromol/L), suggesting the involvement of an endothelium-derived hyperpolarizing factor that activates Ca2+-activated K+ channels. In conclusion, alpha2-adrenoceptor activation caused relaxation of isolated murine mesenteric arteries that was functionally blocked by NO through a mechanism that may involve activation of the soluble guanylate cyclase and cGMP formation. The endothelium-dependent alpha2-adrenoceptor-mediated relaxation is likely to be due to an endothelium-derived hyperpolarizing factor, whose release and/or production is reduced by concurrent NO formation.
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PMID:Nitric oxide inhibits alpha2-adrenoceptor-mediated endothelium-dependent vasodilation. 964 29