MODE AND MECHANISM OF NEUROTENSIN ACTION IN RAT PROXIMAL COLON

This study examined the mechanism of action of neurotensin on intralum inal pressure in rat proximal colon. The direct and indirect contracti le response to neurotensin (100 nM) was abolished in Ca2+-free solutio n, and was antagonized by nifedipine (1-5-10 nM) and potentiated by Ba y K 8644 (methyl -(2-trifluoromethylphenyl)-pyridine-5-carboxylate) (1 0-100-1000 nM). Neurotensin, in the presence of nifedipine (10 nM) and atropine (1 mu M), induced a tetrodotoxin-insensitive inhibitory effe ct, which was antagonized by SR 48692 -quinolinyl)-5-(2,6-dimethoxy-ph enyl)pyrazol-3-yl) carbonyl amino]tricyclo (3.3.1.1.(3.7)) decan-2-car boxylic acid) (300 nM) or apamin (0.1 mu M). The results demonstrate t hat the neurotensin response is dependent on the influx of Ca2+ via L- type channels and results from summation of excitatory and inhibitory effects.