Effects of putative galanin antagonists M35 and C7 on rat exocrine pancreas

Galanin is a neuropeptide having a wide range of biological actions. Recent ly selective galanin receptor antagonists such as M35 [galanin(1-12)-Pro-br adykinin(2-9)-amide] and C7 [galanin(1-12)-Pro-spantide-amide] have been de scribed. These antagonists have blocked the actions of galanin on flexor re flex, glucose-induced insulin secretion, and acetyicholine release from hip pocampus. Our present aim was to investigate whether M35 and C7 can affect galanin-induced inhibition of pancreatic enzyme secretion in rats. Pancreat ic enzyme secretion was studied in urethane-anesthetized rats supplied with jugular vein catheter and pancreatic cannula. Amylase secretion evoked by submaximal CCK-8 stimulation was inhibited dose-dependently by galanin in a nesthetized rats. Surprisingly, neither M35 nor C7 was able to inhibit the responses of the exocrine pancreas to galanin. However, both putative galan in receptor antagonists behaved as agonists in our experimental models. Our data suggest that the effects of galanin on pancreatic enzyme secretion ar e not mediated by M35- or C7-sensitive galanin receptors. Therefore, these galanin receptors are different from those described in the central nervous system. (C) 2001 Elsevier Science Ltd. All rights reserved.