Phorbol esters stimulate somatostatin release from cultured cells

Area of Science:

• Gastroenterology
• Cell Signaling
• Endocrinology

Background:

• Tumor promoters like phorbol esters can activate protein kinase C (PKC).
• PKC is implicated in various cellular signaling pathways, including hormone release.
• Gastric somatostatin plays a crucial role in regulating gastrointestinal function.

Purpose of the Study:

• To investigate the role of PKC in regulating gastric somatostatin release.
• To determine the effects of 12-O-tetradecanoylphorbol 13-acetate (TPA) on canine gastric somatostatin cells.
• To elucidate the signaling mechanisms involved in TPA-induced somatostatin secretion.

Main Methods:

• Isolated canine gastric somatostatin cells were cultured short-term.
• Cells were treated with TPA and other phorbol esters to assess somatostatin release.
• Experiments were conducted with and without extracellular calcium.
• Effects of TPA were examined in combination with forskolin and carbamylcholine.

Main Results:

• TPA significantly stimulated somatostatin release, with an ED50 of 5 x 10(-9) M.
• Phorbol 12,13-dibutyrate (PDBu) also stimulated release, but with lower potency.
• TPA's effect was attenuated by calcium deprivation.
• TPA potentiated forskolin-induced release but not A23187-induced release.
• Carbamylcholine inhibited TPA-induced somatostatin release.

Conclusions:

• PKC activation by TPA is a potent stimulator of gastric somatostatin release.
• Dual signaling pathways appear to regulate somatostatin release, involving both calcium-dependent and independent mechanisms.
• Muscarinic agonists can inhibit TPA-mediated somatostatin secretion, indicating cross-talk between signaling pathways.