A possible role of neurotensin in NANC relaxation of longitudinal muscle of the jejunum and ileum of Wistar rats

The mediators of nonadrenergic, noncholinergic (NANC) relaxation in longitudinal muscle of the jejunum and ileum of Wistar rats were examined in vitro. Treatment of the jejunal and ileal segments with α‐chymotrypsin resulted in decreases in the NANC relaxations induced by electrical field stimulation (EFS) by about one half. The NANC relaxations were also decreased by about one half after the segments had been desensitized to neurotensin. A neurotensin receptor antagonist, SR48692 (10 μM) inhibited the NANC relaxation by 56 and 34% in the jejunal and ileal segments, respectively. An inhibitor of small conductance Ca2+‐activated K+ channel (SK channel), apamin (100 nM) also inhibited the NANC relaxation by 83 and 63%, respectively. Exogenous neurotensin‐induced relaxations of the two segments were abolished by apamin. In the ileal segments, NG‐nitro‐L‐arginine (L‐NOARG, 100 μM), inhibited the NANC relaxation by 43%. L‐NOARG, but not apamin, further inhibited the relaxation which persisted after the desensitization to neurotensin. Apamin with SR48692 inhibited the relaxation only to the same extent as apamin alone. EFS induced inhibitory junction potentials (i.j.ps) in the longitudinal muscle cells of the ileum. I.j.ps consisted of a rapid and a delayed phase. L‐NOARG significantly inhibited only the delayed phase. EFS induced only a rapid i.j.ps in the jejunum. SR48692 and apamin inhibited the i.j.ps. These findings suggest that neurotensin and unknown substance(s) mediate NANC relaxation via SK channels in the jejunum of Wistar rats, and that neurotensin via SK channels and nitric oxide not via SK channels separately mediate the relaxation in the ileum. British Journal of Pharmacology (2002) 137, 629–636. doi:10.1038/sj.bjp.0704914