Characterization of neurotensin receptors in intestinal smooth muscle using a nonpeptide antagonist

Neurotensin reduced substance P-induced tension in ileal muscle strips and the relaxant effect was inhibited by a nonpeptide antagonist, SR 48692, 2-[ (1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxyphenyl)pyrazol-3-yl)carbonylamin o]tricyclo(3.3.1.1(3.7))decan-2-carboxylic acid with a half-maximal concent ration (IC50) of 7.4 +/- 2.1 nM (n = 9) and a dissociation constant (K-b) o f 0.9 +/- 0.2 nM. Neurotensin produced a contractile response in ileal musc le strips pretreated with apamin (50 nM) and in isolated chick rectums and both contractile effects were inhibited by SR 48692 with IC50 of 31.6 +/- 9 .5 nM and K-b of 3.2 +/- 0.9 nM (n = 6) and with IC50 of 28.9 +/- 6.9 nM an d K-b of 5.4 +/- 1.0 nM (n = 7), respectively. The K-b values for the contr actile effects were not significantly different from each other, but signif icantly different from that for the relaxant effect, suggesting that both t ypes of effect are mediated via distinct subtypes of neurotensin receptor i n the intestinal smooth muscles. Contractile responses and excitatory junct ion potentials evoked by electrical stimulation of nonadrenergic, noncholin ergic (NANC) nerves in isolated chick rectums were not inhibited by SR 4869 2 (up to 3.3 mu M). This does not provide functional evidence for the idea that neurotensin acts as an unidentified excitatory neurotransmitter of NAN C nerves in the avian rectum. (C) 1999 Elsevier Science B.V. All rights res erved.