Actions of Helodermatidae venom peptides and mammalian glucagon-like peptides on gastric chief cells.
The actions of peptides (helospectin I, helodermin, exendin-3, exendin-4) that have been isolated from the venoms of Helodermatidae lizards were examined using dispersed chief cells from guinea pig stomach. These actions were compared with those of mammalian glucagon-like peptides, particularly truncated glucagon-like peptide 1 (TGLP-1), a peptide that shares 53% homology with exendin-4. The Helodermatidae venom peptides and TGLP-1 caused a two- to threefold increase in chief cell adenosine 3',5'-cyclic monophosphate and pepsinogen secretion. Exendin-3 and exendin-4 were 100 times more potent than helospectin I and helodermin and 10 times more potent than TGLP-1. Helospectin I and helodermin, but not exendin-4 or TGLP-1, inhibited the binding of 125I-labeled vasoactive intestinal peptide (VIP) and 125I-secretin to dispersed chief cells. The actions of exendin-3, exendin-4, and TGLP-1, but not those of helospectin I, helodermin, VIP, or secretin, were progressively inhibited by increasing concentrations of an exendin-receptor antagonist, exendin-(9-39)-NH2. These data indicate that in gastric chief cells, whereas the actions of helospectin I and helodermin are mediated by interaction with high-affinity secretin (low-affinity VIP) receptors, the actions of exendin-3, exendin-4, and TGLP-1 are mediated by interaction with exendin receptors.
Department of Medicine, State University of New York-Health Science Center, Brooklyn 11203-2098.
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A
Rai
G
G
Singh
R
R
Raffaniello
J
J
Eng
J P
JP
Raufman
D000595:Amino Acid Sequence; D000664:Amphibian Venoms / Q000494:pharmacology*; D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors; D000242:Cyclic AMP / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D005934:Glucagon / Q000235:genetics / Q000494:pharmacology*; D006168:Guinea Pigs; D008116:Lizards; D008297:Male; D008322:Mammals; D008969:Molecular Sequence Data; D010435:Pepsinogens / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D013270:Stomach / Q000166:cytology / Q000187:drug effects*
D000664:Amphibian Venoms; D002147:Calmodulin; D010435:Pepsinogens; D010455:Peptides; D005934:Glucagon; D000242:Cyclic AMP