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-I 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 I-125-labeled vasoactive intestinal peptide (VIP) and I-125-secretin to dispersed chief cells. The actions of exendin-3, exendin-4, and TGLP-1, but not those of helospectin 1, 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.