Effect of the bombesin receptor blockers [Leu13, psi CH2NH-Leu14]bombesin and N-pivaloyl GRP(20-25) alkylamide (L 686,095-001C002) on basal and neuromedin C-stimulated PRL and GH release in pituitary cell aggregates.
Perifusion of rat anterior pituitary cell aggregates, cultured in estrogen-supplemented serum-free medium with 1 nM of the bombesin (BBN)-like peptide, neuromedin C (NMC), significantly stimulates GH and PRL release. This effect is dose-dependently inhibited by the BBN receptor blocker L 686,095-001C002 [an N-pivaloyl-gastrin-releasing-peptide(20-25) alkylamide]. The IC50 was 0.20 nM in the case of the GH response and 0.16 nM in the case of the PRL response. The antagonist has no effect on basal PRL or GH release. [Leu13, psi CH2NH-Leu14]BBN (psi BBN) displays an IC50 of 0.41 microM for inhibiting the GH response and 0.36 microM for inhibiting the PRL response to NMC. At a concentration of 0.5 microM or 5 microM, however, the latter antagonist stimulates PRL and GH release when perifused alone. This stimulatory effect is dose dependent, augments when aggregates are cultured in 1 nM E2 (as is the case for NMC) and is abolished by 2 nM L 686,095-001C002. It is concluded that L 686,095-001C002 is a potent and pure antagonist of pituitary BBN receptors mediating PRL and GH release, whereas psi BBN is a relatively weak antagonist with considerable partial agonist activity.
Houben
H
H
Laboratory of Cell Pharmacology, University of Leuven, School of Medicine, Belgium.
Denef
C
C
D000577:Amides / Q000494:pharmacology; D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013006:Growth Hormone / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D010421:Pentanoic Acids / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000502:physiology
D000577:Amides; D010421:Pentanoic Acids; D010446:Peptide Fragments; D010455:Peptides; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter; C057644:bombesin, Leu(13)-psi-CH2NH-Leu(14)-; C040794:neuromedin C; D011388:Prolactin; D013006:Growth Hormone; D001839:Bombesin