AJP - Gastrointestinal and Liver Physiology, Vol 250, Issue 5 686-G690, Copyright © 1986 by American Physiological Society
Phorbol esters stimulate somatostatin release from cultured cells
K. Sugano, J. Park, A. Soll and T. Yamada
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.
