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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

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)car bonylamino]tricyclo(3.3.1.1.(3.7)decan-2-carboxylic acid with a half-maximal concentration (IC50) of 7.4+/-2.1 nM (n = 9) and a dissociation constant (Kb) of 0.9+/-0.2 nM. Neurotensin produced a contractile response in ileal muscle 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 Kh of 3.2+/-0.9 nM (n = 6) and with IC50 of 28.9+/-6.9 nM and Kb of 5.4+/-1.0 nM (n = 7), respectively. The Kb values for the contractile effects were not significantly different from each other, but significantly different from that for the relaxant effect, suggesting that both types of effect are mediated via distinct subtypes of neurotensin receptor in the intestinal smooth muscles. Contractile responses and excitatory junction potentials evoked by electrical stimulation of nonadrenergic, noncholinergic (NANC) nerves in isolated chick rectums were not inhibited by SR 48692 (up to 3.3 microM). This does not provide functional evidence for the idea that neurotensin acts as an unidentified excitatory neurotransmitter of NANC nerves in the avian rectum.[1]

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