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Tumor promoter inhibition of cellular binding of somatostatin
Abstract:
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.
Insights
Tumor promoting phorbol esters (TPA) reduce somatostatin binding to pancreatic cells by decreasing receptor affinity, not by direct binding. This effect occurs via a pathway similar to secretagogues like caerulein.
Area of Science:
- Endocrinology
- Cell Biology
- Gastroenterology
Background:
- Somatostatin plays a crucial role in regulating pancreatic function.
- Tumor promoting phorbol esters (TPA) are known modulators of cellular processes.
- Understanding TPA's interaction with somatostatin receptors is important for pancreatic research.
Purpose of the Study:
- To investigate the effect of TPA on somatostatin binding to pancreatic acinar cells.
- To elucidate the mechanism by which TPA influences somatostatin receptor affinity.
Main Methods:
- Radioligand binding assays using 125I-[Tyr11] somatostatin on isolated guinea-pig pancreatic acinar cells.
- Investigating the influence of TPA concentration on somatostatin binding.
- Assessing the impact of varying calcium concentrations, temperature, and cell preparation (whole cells vs. membranes).
- Comparing TPA's effect with that of caerulein, a known secretagogue.
Main Results:
- TPA significantly inhibited 125I-[Tyr11] somatostatin binding, with maximal inhibition of 69.7% at 1 microM.
- TPA decreased somatostatin receptor affinity by 2.5-fold, without altering binding capacity.
- The inhibitory effect of TPA was diminished in low calcium, abolished at 4°C, and absent in membrane preparations.
- TPA's effect was not additive to that of caerulein, suggesting a shared or convergent pathway.
Conclusions:
- TPA inhibits somatostatin binding to pancreatic acinar cells primarily by reducing receptor affinity.
- The mechanism of TPA action does not involve direct binding to the somatostatin receptor's active site.
- TPA likely modulates somatostatin receptor affinity through a pathway that overlaps with or is downstream of caerulein's action.