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.
|Journal||American Journal of Physiology - Gastrointestinal and Liver Physiology|
|Issue number||1 28-1|
|State||Published - 1993|
- Gila monster venom
- adenosine 3',5'-cyclic monophosphate
- pepsinogen secretion
- secretin receptors