Participation of nitric oxide in the electrical field stimulation-induced nonadrenergic, noncholinergic (NANC) relaxation in various intestinal regions was studied in 2- to 50-week-old Wistar rats. In the jejunum of 2-week-old rats, the extent of the nitric oxide-mediated component of the relaxation of longitudinal muscle was approximately 60-70%, whereas the component was 40-50% in 4-week-old rats and was absent in 8- and 50-week-old rats. Thus, nitric oxide seems to be the most important mediator at young ages but its significance is lost with age. The same tendency as that in the jejunum was also shown in longitudinal muscle of the ileum, proximal and distal colon, and rectum. The tendency was also shown in the circular muscle of the rectum. Sensitivity of the longitudinal muscle of the jejunum and proximal colon to exogenously added nitric oxide was high in younger rats. Immunoreactive structures for nitric oxide synthase were observed in the circular muscle layer of the rectum. The population of the structures was denser in 4-week-old than that in 50-week-old. The results suggest that NANC relaxation in every region of the intestine at 2-week-old is almost solely mediated by nitric oxide, and its significance as an inhibitory mediator gradually or rapidly decreases with age.

ABSTRACT. Participation of nitric oxide, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP) in nonadrenergic, noncholinergic (NANC) relaxation of longitudinal muscle of various intestinal regions in Sprague Dawley rats (8-weekold) was studied in vitro. Nitric oxide was suggested to participate in NANC relaxation of every intestinal region studied. But the participation was partial and its extent varied among the regions: significant in the proximal colon and rectum, and moderate in the jejunum, ileum and distal colon. Participation of PACAP in NANC relaxation was suggested only in the distal colon, while that of VIP was not detected in any of regions. Results obtained in the present study indicate that extent of participation of nitric oxide in NANC relaxation in Sprague Dawley rat intestine is more significant than those of other strains, Wistar and Wistar-ST.KEY WORDS: NANC (nonadrenergic noncholinergic) relaxation, nitric oxide, PACAP, rat intestine, VIP.J. Vet. Med. Sci. 62(8): 821-828, 2000 Nitric oxide has been suggested to mediate nonadrenergic, noncholinergic (NANC) relaxation in many regions of the gastrointestinal tract [22,23]. However, accumulated evidence suggests that the role of nitric oxide in NANC relaxation is not uniform throughout the gastrointestine, but quite variable in region to region. Wistar-ST rat intestine is a case in point. That is, an essential role of nitric oxide in the relaxation was suggested in circular [11] and longitudinal [24,26] muscles of the proximal colon, and in circular muscle of the rectum [27], while only minor or no role was suggested in longitudinal muscle of the jejunum [19] or the distal colon [16,24], respectively. In addition to regional difference, we recently found a strain difference in the mediator of NANC relaxation of the distal colon of rats between the Sprague Dawley and Wistar-ST strains: nitric oxide was suggested to partially mediate NANC relaxation of the Sprague Dawley but not Wistar-ST strain [21].In addition to nitric oxide, vasoactive intestinal peptide (VIP) is another candidate for the mediator of NANC relaxation in several gastrointestinal regions: lower oesophageal sphincter of opossums [5] and rabbits [2], stomach of dogs [1], guinea pigs [6, 10] and rats [13], taenia coli of guinea pigs [7,10], and colon of rats [9,24]. Pituitary adenylate cyclase activating peptide (PACAP) was also suggested to mediate NANC relaxation in some regions: lower oesophageal sphincter of cats and humans [20], stomach of guinea pigs [14], and colon of guinea pigs [12] and rats [8,15]. We suggested that VIP and PACAP mediate NANC relaxation of longitudinal muscle of the distal colon of Wistar-ST rats via opening of charybdotoxin-and apamin-sensitive K + channels, respectively [15,25]. However, participation of the peptides as well as nitric oxide in NANC relaxation does not seem to be uniform throughout the gastrointestine. For example, neither role of VIP in longitudinal muscle of the proximal and mid colon [24], a...

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Mediators of nonadrenergic, noncholinergic (NANC) relaxation in longitudinal muscle of several regions of ICR mouse intestine were studied. An inhibitor of synthesis of nitric oxide, NG-nitro-L-arginine (L-NOARG) at significantly inhibited NANC relaxations induced by electrical field stimulation (EFS) in the jejunum, ileum, and the proximal and distal colon. Especially in the ileum extent of the inhibition was more than 80%. An antagonist of vasoactive intestinal peptide (VIP) receptors, VIP10-28 at partially inhibited the EFS-induced relaxations in the jejunum and proximal colon, but very slightly in the distal colon and had no effect in the ileum. An antagonist of pituitary adenylate cyclase activating peptide (PACAP) receptor, PACAP6-38 at EFS-induced relaxations in the proximal and distal colon, but not in the jejunum and ileum. Totals of the percentages of relaxant components mediated by nitric oxide, VIP and PACAP in every region are roughly equal to a hundred percent. In another series of experiments, EFS-induced relaxations were almost completely inhibited by the treatment of the segments with L-NOARG and VIP 10-28 10-28 in the jejunum, with L-NOARG, VIP 10_28 10-28 and PACAP6-38 in the proximal colon, and with L-NOARG and PACAP6-38 in the distal colon. The present results suggest that nitric oxide solely mediates the relaxation of longitudinal muscle of the ileum of ICR mice, whereas nitric oxide and VIP co-mediate it in the jejunum, nitric oxide , VIP and PACAP in the proximal colon, and nitric oxide and PACAP in the distal colon .

Abstract. The role of interstitial cells of Cajal (ICC) in electrical field stimulation (EFS)-induced neurogenic responses in ileum was studied by using the ICC-deficient mutant (SLC-W / W V ) mouse and its wild type. In the immunohistochemical study with anti-c-Kit antibody, ICC was observed in the myenteric plexus (MY) and deep muscular plexus (DMP) region in the wild type. In the mutant, ICC-MY were lost, only ICC-DMP were present. EFS induced a rapid contraction of the ileal segments from the wild type mouse in the direction of longitudinal muscle. In the mutant mouse, onset of contraction was delayed and its rate was slowed. EFS induced nonadrenergic, noncholinergic (NANC) relaxation in the presence of atropine and guanethidine in the wild type. A nitric oxide synthase inhibitor inhibited the relaxation and L-arginine reversed it. In the mutant, EFS did not induce NANC relaxation. There was no difference between the responsiveness of the segments from wild type and mutant mice to exogenously added acetylcholine or Nor-1. Taking into account the selective loss of ICC-MY in the mutant mice, it seems likely that ICC-MY have an essential role in inducing nitric oxidemediated relaxation of longitudinal muscle of the mouse ileum and that ICC-MY partly participate in EFS-induced contraction.