Prostaglandin E1 inhibits endocytosis in the β-cell.

Prostaglandins inhibit insulin secretion in a manner similar to that of norepinephrine (NE) and somatostatin. As NE inhibits endocytosis as well as exocytosis, we have now examined the modulation of endocytosis by prostaglandin E-1 (PGE(1)). Endocytosis following exocytosis was recorded by whole-cell patch clamp capacitance measurements in INS-832/13 cells. Prolonged depolarizing pulses producing a high level of Ca2+ influx were used to stimulate maximal exocytosis and to deplete the readily releasable pool (RRP) of granules. This high Ca2+ influx eliminates the inhibitory effect of PGE(1) on exocytosis and allows specific characterization of the inhibitory effect of PGE(1) on the subsequent compensatory endocytosis. After stimulating exocytosis, endocytosis was apparent under control conditions but was inhibited by PGE(1) in a Pertussis toxin-sensitive (PTX)-insensitive manner. Dialyzing a synthetic peptide mimicking the C-terminus of the alpha-subunit of the heterotrimeric G-protein G(z) into the cells blocked the inhibition of endocytosis by PGE(1), whereas a control-randomized peptide was without effect. These results demonstrate that PGE(1) inhibits endocytosis and G(z) mediates the inhibition.