Beta-adrenergic stimulation of anterior pituitary cyclic AMP is enhanced by tumor promoters.
Beta-adrenergic stimulation of cellular cyclic AMP accumulation was characterized in normal anterior pituitary cells in vitro. In the presence of isobutylmethylxanthine, the order of potency of catecholamine agonists, as well as the antagonism by propranolol and not phentolamine, aided in classifying the receptor as beta-adrenergic. Furthermore, this agonist effect was rapidly desensitized. Tumor promoters, which directly activate protein kinase C, enhanced the cyclic AMP levels achieved with beta-adrenergic agonists (1.5-fold average at 10 min). This acute effect occurred over 10-1000 nM phorbol dibutyrate or phorbol myristate acetate. Finally, 3H-phorbol dibutyrate binding to unstimulated anterior pituitary cells was predominantly associated with the cytosol (79%) versus membrane (21%) fractions. Thus, an acute role for protein kinase C in promoting beta-adrenergic receptor activation of adenylate cyclase activity is suggested for anterior pituitary cells.
S N
SN
Perkins
S T
ST
Summers
M J
MJ
Cronin
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D010703:Phorbol Esters; D011943:Receptors, Adrenergic, beta; D015240:Phorbol 12,13-Dibutyrate; D000242:Cyclic AMP; D011493:Protein Kinase C; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine