Galanin inhibits insulin secretion by direct interference with exocytosis.

Electrically permeabilized RINm5F cells were used to study whether galanin inhibits insulin secretion distally to the generation of soluble second messengers. Ca2+-induced insulin secretion was inhibited by the neuropeptide in a dose-dependent manner. Galanin appears to act via a G-protein as pertussis toxin treatment abolished the effect. GTP (100 microM), GDP (100 microM) and a low dose of GTP gamma S (10 microM) did not affect galanin-mediated inhibition of secretion. In contrast, at 100 microM, GTP gamma S attenuated and GDP beta S abolished the effect of the peptide. We conclude that galanin inhibits exocytosis directly by a mechanism involving a G-protein.