Inhibition of mechanical activity by neurotensin in rat proximal colon: involvement of nitric oxide.

ABSTRACT

The aim of the present study was to define the nature of inhibitory action of neurotensin in rat proximal colon. Mechanical activity was detected as changes of intraluminal pressure. Neurotensin (10(-10) to 10(-7) M), in the presence of atropine (10(-6) M), guanethidine (10(-6) M), and nifedipine (10(-8) M), induced a tetrodotoxin-insensitive inhibitory effect characterized by the complete disappearance of the spontaneous phasic contractions. The inhibitory effect of neurotensin (10(-7) M) was abolished by scorpion venom (Leiurus quinquestriatus hebraeus) (10(-6) g/ml) or high K+ (40 mM KCl), whereas it persisted in the presence of omega-conotoxin GVIA, (10(-7) M). N omega-nitro-L-arginine methyl ester (L-NAME) (10(-4) M to 3 x 10(-4) M) antagonized the inhibitory response to neurotensin but did not affect the response to norepinephrine. L-Arginine (5 x 10(-3) M) prevented the effect of L-NAME. The contractile action of neurotensin, observed in the absence of atropine and nifedipine, was potentiated by L-NAME (10(-4) M); L-arginine (5 x 10(-3) M) prevented the L-NAME effect. The present results suggest that in rat proximal colon the inhibitory action of neurotensin is largely due to production of nitric oxide (NO), likely released from neural prejunctional sites. Ca2+ influx through N-type channels is not a required step in the mechanism of neurotensin inhibitory action.