Partial agonist activity of the bombesin-receptor antagonist [Leu14-psi-CH2-NH-Leu13]-bombesin in frog peptic cells.
The pseudopeptide [Leu14-psi-CH2NH-Leu13]-bombesin inhibited 125I-GRP binding to membrane preparations of frog cerebrum and peptic cells, rat cerebral cortex and pancreas with IC50's of 44-250 nM (using 180 pM 125I-GRP). It was unable to stimulate amylase release from rat pancreatic acini, but antagonized competitively BB stimulated amylase release with an IC50 of 130 nM. By contrast the pseudopeptide stimulated pepsinogen secretion from frog esophageal peptic cells with an efficacy relative to bombesin of 36%, and with an EC50 of 30 nM. By virtue of its partial agonist activity it inhibited submaximal BB stimulated responses to a level equal to the pseudopeptide alone. Thus [Leu14-psi-CH2NH-Leu13]-BB differentiates certain BB receptors by exhibiting selective intrinsic efficacy.
Dickinson
K E
KE
Division of Gastroenterology, University of Alabama, Birmingham, AL 35294.
Uemura
N
N
Sekar
M C
MC
McDaniel
H B
HB
Anderson
W
W
Coy
D H
DH
Hirschowitz
B I
BI
D000681:Amylases / Q000378:metabolism; D000818:Animals; D001001:Anura; D001839:Bombesin / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism*; D019886:Gastrin-Releasing Peptide; D005755:Gastrins; D005768:Gastrointestinal Hormones; D009092:Mucous Membrane / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D010435:Pepsinogens / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D051381:Rats; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*
D005755:Gastrins; D005768:Gastrointestinal Hormones; D010435:Pepsinogens; D010455:Peptides; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter; D019886:Gastrin-Releasing Peptide; D000681:Amylases; D001839:Bombesin