Phorbol esters stimulate somatostatin release from cultured cells.
Recent studies suggest that 12-O-tetradecanoylphorbol 13-acetate (TPA), one of a family of phorbol esters that are known tumor promoters, can activate intracellular Ca2+, phospholipid-dependent protein kinase (protein kinase C) directly. To examine the possible involvement of protein kinase C-mediated mechanisms in regulating gastric somatostatin release, we studied the effects of TPA on isolated enriched canine gastric somatostatin cells in short-term culture. TPA markedly stimulated somatostatin release such that nearly 10% of total cellular content of somatostatin was released into media within 2 h of incubation. Among the phorbol compounds tested, TPA was the most potent, with half-maximum effective dose (ED50) obtained at a dose of 5 X 10(-9) M. Phorbol 12,13-dibutyrate (PDBu) also stimulated somatostatin release but with only 5% of the potency of TPA, whereas phorbol compounds with no biological activity in other systems failed to stimulate somatostatin release. In the absence of extracellular Ca2+, the effects of TPA were significantly attenuated. In contrast, stimulation of somatostatin release by forskolin (10(-4) M) was not affected by Ca2+ deprivation but was potentiated by TPA. No such potentiation was observed when TPA was combined with the Ca2+ ionophore A23187. Carbamylcholine (10(-5) M), which inhibits the stimulatory actions of beta-adrenergic agonists or dibutyryl cyclic adenosine monophosphate on somatostatin cells, also inhibited TPA-induced somatostatin release. These data suggest the presence of dual stimulatory mechanisms for gut somatostatin release, both of which are susceptible to inhibition by muscarinic agonists.
Sugano
K
K
Park
J
J
Soll
A
A
Yamada
T
T
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D004285:Dogs; D004357:Drug Synergism; D004533:Egtazic Acid / Q000494:pharmacology; D004789:Enzyme Activation; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D010703:Phorbol Esters; D005576:Colforsin; D013004:Somatostatin; D004533:Egtazic Acid; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium