AJP - Gastrointestinal and Liver Physiology, Vol 265, Issue 1 118-G125, Copyright © 1993 by American Physiological Society
Actions of Helodermatidae venom peptides and mammalian glucagon-like peptides on gastric chief cells
A. Rai, G. Singh, R. Raffaniello, J. Eng and J. P. Raufman
Department of Medicine, State University of New York-Health Science Center, Brooklyn 11203-2098.
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.
