Abstract
Neurotensin (NT) and bradykininin (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 (<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 Tyr 11-Ile 12 is suggested. Carboxyl-blocked neurotensinamide (NT-NH 2) was found to be resistent to proteolysis and not develop tachyphylaxis. No cross-tachyphylaxis was observed between NT and NT-NH 2. The oxytocic effects of NT-NH 2 were markedly potentiated by pre-incubation 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-NH 2 in the rat uterus.
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