TY - JOUR
T1 - Endocrine effects of new bombesin/gastrin-releasing peptide antagonists in rats
AU - Pinski, J.
AU - Yano, T.
AU - Groot, K.
AU - Cai, R. Z.
AU - Radulovic, S.
AU - Schally, A. V.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1992
Y1 - 1992
N2 - 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-ψ(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-ψ(CH2NH)Leu14-bombesin-(6-14) (RC- 3125), and D-Trp6,Leu13-ψ(CH2NH)Phe14-bombesin-(6-14) (RC-3420), but not D-Tpi6,Leu13-ψ(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 μg) immediately before GRP-(14-27) (1 μg) 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.
AB - 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-ψ(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-ψ(CH2NH)Leu14-bombesin-(6-14) (RC- 3125), and D-Trp6,Leu13-ψ(CH2NH)Phe14-bombesin-(6-14) (RC-3420), but not D-Tpi6,Leu13-ψ(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 μg) immediately before GRP-(14-27) (1 μg) 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.
KW - endocrine pancreas
KW - receptor
UR - http://www.scopus.com/inward/record.url?scp=0026785223&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026785223&partnerID=8YFLogxK
U2 - 10.1152/ajpendo.1992.263.4.e712
DO - 10.1152/ajpendo.1992.263.4.e712
M3 - Article
C2 - 1415689
AN - SCOPUS:0026785223
VL - 263
SP - E712-E717
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
SN - 0363-6143
IS - 4 26-4
ER -