GALANIN - STRUCTURE-DEPENDENT EFFECT ON PANCREATIC AMYLASE SECRETION AND JEJUNAL STRIP CONTRACTION

Rat and porcine galanin and their fragments inhibited cholecystokinin- 8 (CCK-8)-stimulated amylase secretion with the following activities: rat galanin-(1-29) = porcine galanin-(1-29) = galanin-(1-15) = rat gal anin-(3-29) > rat galanin-(2-29) = porcine galanin-(2-29) > galanin-(1 -10). Fragments of rat galanin-(9-29) and N(alpha)-acetyl-galanin-(9-2 9) were able to inhibit CCK-8-stimulated pancreatic amylase secretion but only at higher dose levels. Porcine galanin-(15-29) and rat galani n-(21-29) were unable to produce significant inhibition. Rat and porci ne galanin-(1-29), galanin-(1-15) and rat N(alpha)-acetyl-galanin-(9-2 9) also inhibited basal pancreatic amylase secretion. In the rat jejun al strip contraction model, rat galanin-(1-29) and porcine galanin-(1- 29) have similar potencies. Galanin-(1-15) and galanin-(1-10) stimulat e rat jejunal strip contraction with decreasing potencies. Elimination of Gly1 from the N-terminus of both rat and porcine galanin had no si gnificant effect either on pancreatic amylase secretion or on jejunal strip contraction. The rat galanin-(3-29) and (9-29) are not active in the stimulation of rat jejunal strip contraction. Acetylation of porc ine galanin-(9-29) created a peptide that was a powerful stimulator of rat jejunal strip contraction. The present data indicate that N-termi nal rat galanin amino acid residues are crucial for rat jejunal strip contraction but are not required for inhibition of pancreatic amylase. These results suggest that the galanin amino acid sequence contains s everal specific domains, which can be recognized by specific galanin r eceptor subsets.