GRP-preferring bombesin receptors increase generation of inositol phosphates and tension in rat myometrium
Amiot, F.; Leiber, D.; Marc, S.; Harbon, S.
American Journal of Physiology 265(6 Pt 1): C1579-C1587
1993
ISSN/ISBN: 0002-9513 PMID: 8279518 Document Number: 414863
In the estrogen-treated rat myometrium, bombesin (Bn) and related agonists triggered contraction and the increased generation of inositol phosphates. The relative order of potencies was identical for both responses: Bn = gastrin releasing peptide (GRP) = litorin = neuromedin C mchgt neuromedin B. Two specific GRP-preferring receptor antagonists, namely (D-Phe6)Bn-(6-13) methyl ester and (Leu-14,psi-13-14)Bn were inhibitory for both Bn-mediated tension and generation of inositol phosphates. (125I-Tyr-4)Bn bound to myometrial membranes with high affinity (K-d = 104 pM) to a single class of sites in a saturable and reversible manner. The relative potencies for inhibiting binding were GRP = litorin = (Tyr-4)Bn (K-i = 0.4 to 0.6 nM) mchgt neuromedin B (K-i 10.3 nM). The high affinity displayed by (D-Phe6)Bn-(6-13) methyl ester (K-i = 2.8 nM) and (Leu-14,psi-13-14)Bn (K-i = 35 nM) for competing for (Tyr-4)Bn binding supported the involvement of a GRP-preferring Bn receptor. Guanine nucleotides decreased the binding of (125I-Tyr-14)Bn and accelerated the rate of ligand dissociation, reflecting the coupling of receptors to guanine nucleotide regulatory proteins (G proteins). The results demonstrate that rat myometrium expresses functional GRP-preferring Bn receptors whose activation stimulates the phospholipase C pathway, a pertussis toxin-insensitive event that contributes to Bn-mediated uterine contractions.