TY - JOUR
T1 - Actions of Helodermatidae venom peptides and mammalian glucagon-like peptides on gastric chief cells
AU - Rai, A.
AU - Singh, G.
AU - Raffaniello, R.
AU - Eng, J.
AU - Raufman, J. P.
PY - 1993
Y1 - 1993
N2 - 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.
AB - 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.
KW - Gila monster venom
KW - adenosine 3',5'-cyclic monophosphate
KW - exendins
KW - glucagon
KW - helodermin
KW - helospectin
KW - pepsinogen secretion
KW - secretin receptors
UR - http://www.scopus.com/inward/record.url?scp=0027180014&partnerID=8YFLogxK
U2 - 10.1152/ajpgi.1993.265.1.g118
DO - 10.1152/ajpgi.1993.265.1.g118
M3 - Article
C2 - 8393295
AN - SCOPUS:0027180014
VL - 265
SP - G118-G125
JO - American Journal of Physiology - Gastrointestinal and Liver Physiology
JF - American Journal of Physiology - Gastrointestinal and Liver Physiology
SN - 0193-1857
IS - 1 28-1
ER -