Neurotensin is a potent inhibitor of guinea-pig colon contractile activity.

The investigation concerned the effects of neurotensin (NT) on the mechanical activity of segments of guinea-pig proximal colon. The peptide, in concentrations ranging from 0.1 nM to 100 nM, induced a quick relaxation of the preparations which was followed upon washout by a rebound contraction. Tetrodotoxin had no effect on either the NT-induced relaxation or the rebound contraction. Blocking agents of alpha- and beta-adrenoceptors were also without effect. The bee venom toxin apamin inhibited and even converted to contractions the NT-induced relaxations in the guinea-pig colon. Concentration-response curves for the inhibitory effect of NT, adrenaline and ATP indicated that NT (IC50 0.32 nM) was 100 times more potent than adrenaline (IC50 nM) and 50 000 times more potent than ATP (IC50 16 microM). The data show that NT exerts a potent myogenic relaxing effect on the longitudinal smooth muscle of the guinea-pig proximal colon. The properties of this effect suggest the presence of high affinity NT receptors on colonic smooth muscle cells and this points to a possible role for NT as a modulator of guinea-pig proximal colon motility.