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

Abstract

1 The mediators of nonadrenergic, noncholinergic (NANC) relaxation in longitudinal muscle of the jejunum and ileum of Wistar rats were examined in vitro. 2 Treatment of the jejunal and ileal segments with a-chymotrypsin resulted in decreases in the NANC relaxations induced by electrical ®eld stimulation (EFS) by about one half. 3 The NANC relaxations were also decreased by about one half after the segments had been desensitized to neurotensin. A neurotensin receptor antagonist, SR48692 (10 mM) inhibited the NANC relaxation by 56 and 34% in the jejunal and ileal segments, respectively. 4 An inhibitor of small conductance Ca 2+ -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. 5 In the ileal segments, N G -nitro-L-arginine (L-NOARG, 100 mM), 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. 6 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 signi®cantly inhibited only the delayed phase. 7 EFS induced only a rapid i.j.ps in the jejunum. SR48692 and apamin inhibited the i.j.ps. 8 These ®ndings 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.

Participation of ATP in Nonadrenergic, Noncholinergic Relaxation of Longitudinal Muscle of Wistar Rat Jejunum

“…In the presence of atropine (1 mM) and guanethidine (5 m M), EFS with two pulses of 20-Hz frequency at 20 V induced mono-phasic rapid i.j.ps. The i.j.ps were completely inhibited by apamin as shown previously (23). SR48692 at 10 m M also partially inhibited the i.j.ps and resulted in about 30% inhibition 20 min after treatment, i.j.ps in the absence or presence of SR48692 were 12.6 ± 1.6 mV (n = 8) or 8.8 ± 2.0 mV (n = 8, significantly different from the value in the absence, P<0.05), respectively (Fig.…”

“…It was previously shown that apamin significantly inhibited EFS (10 Hz)-induced relaxation of the jejunal segments by 83% (23). Apamin at 100 nM completely inhibited the relaxation at 1.0 Hz (Table 1).…”

“…Participation of VIP in the relaxation of the distal colon of 2-to 8-week-old Wistar rats was also demonstrated (28). Although participation of neurotensin in the relaxation induced at 1 Hz was shown to be of a similar magnitude to those at higher frequencies in the Wistar rat jejunum with the desensitization method (23), further detailed examination with a neurotensin receptor antagonist in the present study revealed little effect of neurotensin at 1 Hz, instead of a significant role at higher frequencies (Fig. 3A).…”

“…In our previous studies, neurotensin was reported to partially mediate NANC relaxation in the rat jejunum and ileum (23). We therefore examined the relationship between relaxations mediated by ATP and neurotensin.…”

“…Although the effect of apamin on i.j.ps induced by more pulses was not examined for technical reasons, we have shown ATP-mediated apaminsensitive relaxation concomitant with apamin-sensitive fast i.j.ps in the Wistar rat jejunum. We previously reported PACAP-mediated apamin-sensitive relaxation concomitant with apamin-sensitive fast i.j.ps in the Wistar-ST rat distal colon (32,33) and neurotensinmediated relaxation in the Wistar rat proximal jejunum (23). It was also suggested that an unknown peptide-like substance induced apamin-sensitive relaxation with apamin-sensitive fast i.j.ps in the Wistar-ST rat jejunum (34).…”