title: Comparison of prolonged in vivo inhibitory activity of several potent bombesin (BN) antagonists on BN-stimulated amylase secretion in the rat.
abstract: New BN analogues designed to be competitive receptor antagonists at the BN/gastrin releasing peptide receptor(s) can exhibit diverse properties ranging from full antagonist, partial agonist or weak agonist activity, depending on the assay system and animal species employed. Here we evaluate the following 3 antagonists which have the most potent receptor affinities in several in vitro assay systems and are representative of 3 main classes of BN antagonists for their in vivo effects on pancreatic amylase secretion in the rat: [D-Cpa6,Phe14,psi 13-14]BN(6-14), [D-Phe6]BN(6-13) propylamide, and [D-Phe6]BN(6-13) methyl ester. After injection in the rat, the methyl ester was clearly the most potent antagonist and completely inhibited BN-stimulated amylase release at the 20 nmol/kg (IV bolus) for about 2 h. In contrast, the propylamide analogue at the 200 nmol/kg (IV bolus) dose produced incomplete inhibition of amylase release. Inhibition was transient and lasted for only about 1 h, possibly reflecting the significant agonist activity of this latter peptide in the rat pancreatic amylase secretion test in vitro. The psi-analogue, while being the longest acting analogue, was also incapable of lowering amylase to basal level at 50 times the BN dose, suggesting that it is a mixed agonist-antagonist in vivo as was also previously shown in vitro in the rat.
authors.affiliation: Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70112.
authors.forename: N
authors.initials: N
authors.lastname: Alptekin
authors.forename: R V
authors.initials: RV
authors.lastname: Yagci
authors.forename: A
authors.initials: A
authors.lastname: Ertan
authors.forename: N Y
authors.initials: NY
authors.lastname: Jiang
authors.forename: J C
authors.initials: JC
authors.lastname: Rice
authors.forename: M
authors.initials: M
authors.lastname: Sbeiti
authors.forename: W J
authors.initials: WJ
authors.lastname: Rossowski
authors.forename: D H
authors.initials: DH
authors.lastname: Coy
mesh_terms: D000681:Amylases / Q000378:metabolism*; D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051381:Rats
chemical_list: D000681:Amylases; D001839:Bombesin