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-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.
| Original language | English |
|---|---|
| Journal | American Journal of Physiology - Endocrinology and Metabolism |
| Volume | 263 |
| Issue number | 4 26-4 |
| State | Published - Jan 1 1992 |
| Externally published | Yes |
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Keywords
- endocrine pancreas
- receptor
ASJC Scopus subject areas
- Biochemistry
- Endocrinology
- Physiology
Cite this
Endocrine effects of new bombesin/gastrin-releasing peptide antagonists in rats. / Pinski, J.; Yano, T.; Groot, K.; Cai, R. Z.; Radulovic, S.; Schally, Andrew V.
In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 263, No. 4 26-4, 01.01.1992.Research output: Contribution to journal › Article
}
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, Andrew V
PY - 1992/1/1
Y1 - 1992/1/1
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
M3 - Article
C2 - 1415689
AN - SCOPUS:0026785223
VL - 263
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
SN - 0363-6143
IS - 4 26-4
ER -