title: Endocrine effects of new bombesin/gastrin-releasing peptide antagonists in rats.
abstract: Four new and specific pseudononapeptide bombesin/gastrin-releasing peptide (GRP) receptor antagonists, containing the D-forms of Trp or Trp analogue (Tpi) at position 6, were studied for their effects on the endocrine pancreas and GRP-(14-27)-induced gastrin release in pentobarbital-anesthetized rats. One of the analogues, D-Tpi6,Leu13-psi (CH2NH)Leu14-bombesin-(6-14) (RC-3095), was injected into the lateral brain ventricle just preceding intracerebroventricular administration of GRP-(14-27) to evaluate its antagonistic effect on GRP-induced serum growth hormone (GH) suppression. Analogues RC-3095, D-Trp6,Leu13-psi (CH2NH)Leu14-bombesin-(6-14) (RC-3125), and D-Trp6,Leu13-psi (CH2NH)Phe14-bombesin-(6-14) (RC-3420), but not D-Tpi6,Leu13-psi (CH2NH)Phe14-bombesin-(6-14) (RC-3105), significantly (P < 0.01) inhibited GRP-(14-27)-stimulated serum gastrin secretion. Analogues RC-3095, RC-3420, and RC-3105, but not RC-3125, demonstrated significant (P < 0.05) antagonistic activities on GRP-(14-27)-stimulated plasma glucagon secretion. Intracerebroventricular injection of RC-3095 (10 micrograms) immediately before GRP-(14-27) (1 microgram) completely prevented the GRP-(14-27)-induced serum GH suppression. These results indicate that 1) marked differences exist in the ability of these analogues to antagonize GRP-(14-27)-induced gastrin or glucagon release, suggesting the existence of different bombesin/GRP receptor subtypes, and 2) the central effect of bombesin/GRP on GH release from the pituitary is probably mediated through specific bombesin/GRP receptors.
authors.affiliation: Endocrine, Polypeptide and Cancer Institute, Department of Veterans Affairs Medical Center, New Orleans, Louisiana.
authors.forename: J
authors.initials: J
authors.lastname: Pinski
authors.forename: T
authors.initials: T
authors.lastname: Yano
authors.forename: K
authors.initials: K
authors.lastname: Groot
authors.forename: R Z
authors.initials: RZ
authors.lastname: Cai
authors.forename: S
authors.initials: S
authors.lastname: Radulovic
authors.forename: A V
authors.initials: AV
authors.lastname: Schally
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001839:Bombesin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004702:Endocrine Glands / Q000187:drug effects*; D019886:Gastrin-Releasing Peptide; D005755:Gastrins / Q000097:blood; D005934:Glucagon / Q000097:blood; D013006:Growth Hormone / Q000097:blood; D007328:Insulin / Q000097:blood; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D005755:Gastrins; D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides; C071363:bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-; D019886:Gastrin-Releasing Peptide; C041922:gastrin releasing peptide (14-27); D013006:Growth Hormone; D005934:Glucagon; D001839:Bombesin