NEUROTENSIN - CONTRACTILE ACTIVITY, SPECIFIC BINDING, AND LACK OF EFFECT ON CYCLIC-NUCLEOTIDES IN INTESTINAL SMOOTH-MUSCLE

Neurotensin contracted the isolated longitudinal smooth muscle strip of the guinea-pig intestine. It induced a biphasic response (relaxation followed by contraction) when the muscle was contracted by histamine. Tetrodoxin blocked the contraction and the contraction phase of the biphasic response. Dose responses of the relaxing effect of neurotensin and its analogs D-Arg8-neurotensin and D-Arg9-neurotensin on tetrodotoxin-treated muscle gave EC50 values of 5 nM, 5.5 nM and 110 nM for the three peptides, respectively. [3H]Neurotensin bound specifically to membranes prepared from isolated longitudinal muscle strips of the guinea-pig intestine. In binding studies using [3]Hneurotensin and unlabelle peptides, the KDs of neurotensin, D-Arg8-neurotensin and D-Arg9-neurotensin were 4 nM, 2 nM and 300 nM, respectively, values which are in close agreement with the EC50 of the three peptides. Neurotensin had no effect on the cAMP and cGMP contents in longitudinal intestinal muscle strips of the guinea pig, an observation which suggests that cyclic nucleotides are not involved in the mechanism of action of neurotensin in this muscle preparation. © 1979.