Tumor promoter inhibition of cellular binding of somatostatin.

Tumor promoting phorbol esters inhibited the binding of 125I-[Tyr11] somatostatin to isolated acinar cells from guinea-pig pancreas. Maximal inhibition reached 69.7 +/- 5% at 1 microM TPA. Receptor affinity was decreased by 2.5-fold without change in binding capacity. The ability of TPA in inhibiting somatostatin binding was decreased in 30 nM Ca2+ medium, abolished at 4 degrees C or in a membrane preparation. The effect of caerulein, a secretagogue which also caused loss of binding, and that of TPA were not additive. We concluded that TPA inhibits somatostatin binding not by binding directly at the active site of somatostatin receptor. TPA may act at a later point than caerulein via a similar pathway to modulate somatostatin receptor affinity.