Effects of neurotensin on the isolated mouse distal colon

The effects of neurotensin were studied in the isolated mouse distal colon. This peptide had potent stimulatory effects which were of pre- or postjunctional origin according to the concentrations used. At low concentrations (10(-11)-10(-10) M) neurotensin induced neurogenic non-cholinergic contractions which seemed to result from the release of substance P (or substance P-like activity) by enteric excitatory nerves. At higher concentrations (10(-9)-10(-7) M) neurotensin elicited a biphasic effect consisting of transient relaxation rapidly followed by myogenic contraction. The bee venom toxin apamin inhibited the NT-induced relaxation while inhibition of prostaglandin synthesis by indomethacin abolished the contraction phase. All these responses were tightly related to the extracellular Ca2+ concentration. These properties of neurotensin point to a possible role for this peptide as a modulator of colonic motility.