Galanin exerts dual action on inositol-specific phospholipase C activity in isolated pancreatic islets.
The intracellular mechanism whereby the neuropeptide galanin inhibits insulin secretion is not establish, since the peptide affects several 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 generation of inositol 1,4,5-trisphosphate and its metabolite inositol 1,3,4-trisphosphate from the hydrolysis of polyphosphoinositides. Inositol phosphates were measured by anion-exchange fast protein liquid chromatography (FPLC) analysis of extracts from islets prelabelled with myo-3H-inositol. Galanin (1 to 100 nM) significantly increased the glucose-induced (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, both the stimulatory and inhibitory effects of galanin on the iPLC activity vanished. We therefore conclude that galanin initially stimulates iPLC 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.
Malm
D
D
Department of Medicine, University Hospital of Tromsoe, Norway.
Lindskog
S
S
Ahrén
B
B
Florholmen
J
J
D000818:Animals; D002469:Cell Separation; D004789:Enzyme Activation / Q000187:drug effects; D019004:Galanin / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013379:Substrate Specificity / Q000187:drug effects; D010738:Type C Phospholipases / Q000187:drug effects* / Q000378:metabolism
D015544:Inositol 1,4,5-Trisphosphate; D019004:Galanin; D010738:Type C Phospholipases