Effects of alpha 2-adrenergic agonists on carbachol-stimulated catecholamine synthesis in cultured bovine adrenal medullary cells.
We examined the effects of alpha 2- and alpha 1-adrenergic agonists on synthesis of catecholamines in cultured bovine adrenal medullary cells. Clonidine, an alpha 2-adrenergic agonist, inhibited carbachol-stimulated synthesis of [14C]catecholamines from [14C]tyrosine in a concentration-dependent manner. Clonidine also inhibited carbachol-induced uptake of 45Ca2+ into cells at concentrations similar to those that inhibited the synthesis of [14C]catecholamines. Other alpha 2-adrenergic agonists, oxymetazoline and guanfacine, also strongly inhibited carbachol-stimulated synthesis of [14C]catecholamines. alpha 1-Adrenergic agonists, phenylephrine and norfenefrine, did not affect the synthesis. Tyrosine hydroxylase (EC 1.14.16.2) activity in a soluble fraction of cultured bovine adrenal medullary cells was assayed after gel filtration on a Sephadex G-25 column. Stimulation of the cells with carbachol increased the activity of tyrosine hydroxylase. Clonidine, oxymetazoline, and guanfacine all suppressed the carbachol-induced increase in activity of tyrosine hydroxylase in the cells. These results suggest that alpha 2-adrenergic agonists inhibit carbachol-stimulated synthesis of catecholamines by suppression of tyrosine hydroxylase activity, probably through the inhibition of Ca2+ uptake. However, the involvement of alpha 2-adrenoceptors in the inhibitory effects of alpha 2-agonists on catecholamine synthesis is still unsettled, since yohimbine failed to antagonize the inhibitory effect of clonidine on the synthesis in cultured bovine adrenal medullary cells.
D015078:2-Hydroxyphenethylamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology*; D002395:Catecholamines / Q000096:biosynthesis*; D002417:Cattle; D002478:Cells, Cultured; D003000:Clonidine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016316:Guanfacine; D006146:Guanidines / Q000494:pharmacology; D009655:Octopamine / Q000031:analogs & derivatives*; D010109:Oxymetazoline / Q000494:pharmacology; D010648:Phenylacetates / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D002395:Catecholamines; D006146:Guanidines; D010648:Phenylacetates; D009655:Octopamine; D015016:Yohimbine; D016316:Guanfacine; D014443:Tyrosine; D015078:2-Hydroxyphenethylamine; D010109:Oxymetazoline; D002217:Carbachol; C005310:norfenefrine; D000242:Cyclic AMP; D014446:Tyrosine 3-Monooxygenase; D003000:Clonidine; D002118:Calcium