INHIBITION OF MECHANICAL-ACTIVITY BY NEUROTENSIN IN RAT PROXIMAL COLON - INVOLVEMENT OF NITRIC-OXIDE

The aim of the present study was to define the nature of inhibitory ac tion of neurotensin in rat proximal colon. Mechanical activity was det ected 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 inhib itory effect characterized by the complete disappearance of the sponta neous 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 pr esence of omega-conotoxin GVIA (10(-7) M). N-omega-nitro-L-arginine me thyl ester (L-NAME) (10(-4) M to 3 x 10(-4) M) antagonized the inhibit ory response to neurotensin but did not affect the response to norepin ephrine. L-Arginine (5 x 10(-3) M) prevented the effect of L-NAME. The contractile action of neurotensin, observed in the absence of atropin e 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 t hat in rat proximal colon the inhibitory action of neurotensin is larg ely due to production of nitric oxide (NO), likely released from neura l prejunctional sites. Ca2+ influx through N-type channels is not a re quired step in the mechanism of neurotensin inhibitory action.