GALANIN EXERTS DUAL-ACTION ON INOSITOL-SPECIFIC PHOSPHOLIPASE-C ACTIVITY IN ISOLATED PANCREATIC-ISLETS

The intracellular mechanism whereby the neuropeptide galanain inhibits insulin secretion is not established, since the peptide affects sever al signal pathways, including intracellular messengers such as calcium and cyclic AMP. In this study, we have assessed the effect of galanin on the inositol-specific phospholipase C (iPLC) activity in isolated rat pancreatic islets. The iPLC activity was measured as the generatio n of inositol 1,4,5-trisphosphate and its metabolite inositol 1,3,4-tr isphosphate from the hydrolysis of polyphosphoinositides. Inositol pho sphates were measured by anion-exchange fast protein liquid chromatogr aphy (FPLC) analysis of extracts from islets prelabelled with myo-H-3- inositol. Galanin (1 to 100 nM) significantly increased the glucose-in duced (12 mM) accumulation of inositol 1,4,5-trisphosphate after 2 min , but this stimulation of iPLC activity was followed by a significant suppression after 15 min. In the absence of extracellular calcium, bot h the stimulatory and inhibitory effects of galanin on the iPLC activi ty vanished. We therefore conclude that galanin initially stimulates i PLC in a calcium-dependent manner, followed by a secondary inhibitory effect. The secondary inhibition of iPLC activity might contribute to the insulinostatic action of the neuropeptide.