Phorbol ester and central chemosympathectomy augment beta-adrenoceptor response by different mechanisms.
The aim of this study was to compare the mechanisms of increased responsiveness of the beta-adrenoceptor dependent cyclic AMP generating system induced by chronic decrease of noradrenaline availability (beta-upregulation) with that resulting from simultaneous stimulation of alpha-adrenoceptors (alpha-potentiation) and to assess the role of protein kinase C in these phenomena. The beta-upregulation was produced by central chemosympathectomy with 6-hydroxydopamine. The role of alpha 1- and alpha 2-adrenoceptors was assessed by comparison of the effects of specific beta-adrenoceptor agonist isoproterenol with those of a mixed alpha-beta-adrenoceptor agonist noradrenaline, and clonidine was used to selectively stimulate alpha 2-adrenoceptors. The role of protein kinase C was assessed by measuring cyclic AMP responses in the presence and absence of 12-O-tetradecanoyl-phorbol 13-acetate. The results indicate that the mechanism of increased responsiveness induced by central chemosympathectomy is different from the alpha-potentiation, that only alpha 1-adrenoceptors are involved positively in alpha-potentiation, while the alpha 2-adrenoceptors play an inhibitory role, and that increased responsiveness following central chemosympathectomy may be inhibited by protein kinase C activation.
Nalepa
I
I
Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Vetulani
J
J
D000818:Animals; D001921:Brain / Q000502:physiology*; D003000:Clonidine / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D008297:Male; D016627:Oxidopamine; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013563:Sympathectomy, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D016627:Oxidopamine; D000242:Cyclic AMP; D011493:Protein Kinase C; D003000:Clonidine; D013755:Tetradecanoylphorbol Acetate