Effects of a novel bombesin antagonist analogue on bombesin-stimulated gastric acid secretion and growth hormone release in the pentobarbital-anesthetized rat.
A new and specific bombesin receptor antagonist analogue, Leu13 psi [CH2NH]Leu14-bombesin, was studied for inhibition of bombesin-stimulated gastric acid secretion in pentobarbital-anesthetized rats. The analogue potently inhibited bombesin-stimulated gastric acid secretion in a dose-dependent fashion, exhibiting an ID50 of 0.66 mumol/250 g, which corresponds to a molar ratio of bombesin to antagonist of approximately 1:12. This agrees well with antagonist to agonist potency ratios previously reported for inhibition of bombesin-stimulated amylase release from guinea pig pancreatic acinar cells and the growth of murine Swiss 3T3 cells, suggesting functional similarities between the receptor sites involved. Conversely, the analogue failed to inhibit bombesin inhibition of growth hormone release in the sodium pentobarbital-anesthetized rat model and was, in fact, a weak agonist at higher dose levels. This indicates either that this system is not particularly bombesin-specific or that bombesin receptor recognition and signaling requirements are substantially different in the gut and hypothalamus.
Rossowski
W J
WJ
Dept. of Medicine, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Murphy
W A
WA
Jiang
N Y
NY
Yeginsu
O
O
Ertan
A
A
Coy
D H
DH
D000818:Animals; D001839:Bombesin / Q000008:administration & dosage*; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D013006:Growth Hormone / Q000378:metabolism*; D007275:Injections, Intravenous; D010424:Pentobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter / Q000187:drug effects*
D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter; D013006:Growth Hormone; D010424:Pentobarbital; D001839:Bombesin