Pharmacological effects and metabolism of neurotensin and bradykinin in the isolated rat uterus.
Neurotensin (NT) and bradykinin (BK) were found to cause contractions of isolated rat uterus preparations. In 97% of the experiments, acute tachyphylaxis followed soon after the initial administration of NT. Interrelation between the oxytocic effects of NT and BK was not observed. Among the NT fragments studied, only NT-(9-13) had an oxytocic effect (less than 1.0%). All NT fragments tested induced tachyphylaxis to NT regardless of their efficacy. Using HPLC analysis, NT but not BK was found to be degraded by the intact rat uterus. A major involvement of a carboxydipeptidase cleaving at Tyr11-Ile12 is suggested. Carboxyl-blocked neurotensinamide (NT-NH2) was found to be resistent to proteolysis and not develop tachyphylaxis. No cross-tachyphylaxis was observed with NT or NT-(1-11). The results suggest the existence of different receptors for NT and BK in the uterus, as well as the existence of different receptors or receptor states that interact with NT or NT-NH2 in the rat uterus.
Lebrun
I
I
Department of Pharmacology, School of Medicine of Riberao Preto, University of Sao Paulo, Brazil.
Camargo
A C
AC
Correa
F M
FM
D000818:Animals; D001920:Bradykinin / Q000378:metabolism / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D066298:In Vitro Techniques; D009496:Neurotensin / Q000378:metabolism / Q000494:pharmacology*; D010121:Oxytocin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014357:Trypsin / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
D009496:Neurotensin; D010121:Oxytocin; D014357:Trypsin; D001920:Bradykinin