title: The effect of helodermin in rat dispersed pancreatic acini.
abstract: Helodermin is a 35 amino acid-residue peptide of the vasoactive intestinal polypeptide (VIP) family, which was originally isolated from the venom of Heloderma suspectum on the basis of its capacity to stimulate adenylate cyclase in the rat pancreas. In the present study, using rat dispersed pancreatic acini, we examined the binding characteristics of helodermin, its action on amylase secretion, and the production of intracellular cyclic AMP (cAMP). Helodermin stimulated intracellular cAMP production dose dependently in a manner that was nearly identical to that of VIP. Helodermin stimulated amylase secretion dose dependently, showing an efficacy similar to that of VIP but with 100 times less potency than VIP. Adding 0.5 mM 3-isobutyl-1-methylxanthine increased the potency of helodermin's action on amylase secretion but did not change the efficacy. The binding study showed that the order of binding affinity to VIP receptors was VIP = helodermin > secretin, while the order of that to secretin receptors was secretin > helodermin > VIP. These results suggest that helodermin stimulated amylase secretion from rat dispersed pancreatic acini via VIP-preferring receptors that are coupled to the production of intracellular cAMP, but a part of the postreceptor mechanism for enzyme secretion is different from that of VIP.
authors.affiliation: Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Kashimura
authors.forename: T
authors.initials: T
authors.lastname: Shimosegawa
authors.forename: T
authors.initials: T
authors.lastname: Mochizuki
authors.forename: N
authors.initials: N
authors.lastname: Yanaihara
authors.forename: M
authors.initials: M
authors.lastname: Koizumi
authors.forename: T
authors.initials: T
authors.lastname: Toyota
mesh_terms: D000681:Amylases / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D014660:Vasoactive Intestinal Peptide / Q000187:drug effects / Q000378:metabolism
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D014660:Vasoactive Intestinal Peptide; C040442:heliodermin; D000242:Cyclic AMP; D000681:Amylases