AJP - Gastrointestinal and Liver Physiology, Vol 251, Issue 5 602-G610, Copyright © 1986 by American Physiological Society
Receptors involved in helodermin action on rat pancreatic acini
J. P. Dehaye, J. Winand, C. Damien, F. Gomez, P. Poloczek, P. Robberecht, A. Vandermeers, M. C. Vandermeers-Piret, M. Stievenart and J. Christophe
Helodermin is a new peptide isolated from the venom of Heloderma suspectum.
Its effects on rat pancreatic acini were compared with those of secretin
and vasoactive intestinal peptide (VIP). Four classes of receptors with
decreasing affinity for secretin (S1, S2, S3, and S4) were first
delineated. Occupancy of S1 and S2 by secretin was responsible for a
biphasic adenosine 3',5'-cyclic monophosphate (cAMP) response. S3 was VIP
preferring so that the VIP-induced increase in cAMP could be inhibited by
VIP-(10-28). S2 and S3 allowed cAMP elevation, protein phosphorylation,
weak secretory effects, and potentiation of cholecystokinin octapeptide
(CCK-8) when occupied by secretin and VIP, respectively. A more efficient
exocytosis was observed with secretin interacting with low-affinity
receptors S4. Helodermin increased cAMP levels 14-fold, this increase being
inhibited by VIP-(10-28). Low concentrations of helodermin stimulated
amylase secretion twofold and potentiated secretion by CCK-8. High
concentrations of helodermin stimulated secretion another 2.6-fold.
Helodermin bound to the four secretin receptors with a weak selectivity. At
low concentration, helodermin stimulated cAMP elevation, protein
phosphorylation, amylase release, and potentiation of CCK-8 through S3,
whereas at high concentration it stimulated secretion via S4.
