Pharmacological characterization of [Leu-13-psi-CH2NH-Leu14]-bombesin as a specific bombesin receptor antagonist on isolated smooth muscle cells.
Isolated smooth muscle cells from guinea pig stomach were used to study the pharmacological characteristics of a newly synthetized bombesin analog, [Leu13-psi-CH2NH-Leu14]-bombesin (psi 13,14-BN) to function as antagonist of bombesin-induced contractile response. The antagonism caused by this new analog was compared to that obtained with the substance P analog [D-Arg1,D-Pro2,D-Trp7,9,Leu11]Substance P [( APTTL]SP), which has been used until now to characterize bombesin receptors on smooth muscle cells. psi 13,14-BN resulted to be more potent than [APTTL]SP as antagonist of bombesin action on smooth muscle. Comparing the IC50, psi 13,14-BN (IC50 70 nM) was 8 times more potent than [APTTL]SP (IC50 600 nM). In contrast to [APTTL] SP, the action of psi 13,14-BN was shown to be specific toward bombesin receptors in that it does not interfere with receptors for other agents (i.e., cholecystokinin, acetylcholine or substance P). The antagonism induced by both compounds was competitive inasmuch as the slope of the regression lines obtained by Schild plot analysis were not significantly different from the unity. The apparent affinity for the bombesin receptor was 0.8 nM for psi 13,14-BN and 7.8 nM for [APTTL]SP. These results indicate that psi 13,14-BN acts on isolated gastric smooth muscle cells as a competitive bombesin receptor antagonist, with a higher affinity and specificity than the substance P analog used previously.
Severi
C
C
Gastroenterology Unit, University La Sapienza, Rome, Italy.
Coy
D H
DH
Jensen
R T
RT
Boschero
L
L
Anania
M C
MC
Delle Fave
G
G
D000818:Animals; D001839:Bombesin / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D013270:Stomach / Q000187:drug effects; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology
D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter; C057644:bombesin, Leu(13)-psi-CH2NH-Leu(14)-; D013373:Substance P; D001839:Bombesin