Sosogu Nakayama

Sympathetic activity in the recto-rectal reflex of the guinea pig.

In the guinea pig, defecation is controlled by the myenteric plexus, whose activity is modulated by the sacral spinal and supraspinal centers. The purpose of this study is to clarify the control of defecation reflex by sympathetic nerves. The propulsive contractions of the rectum produced by rectal distension (recto-rectal excitatory reflex response) were abolished after transection of the Th 13 and/or the L 4 segment. This response was reproduced again after removal of the lumbar segments (L1-4), division of the lumbar dorsal roots (L1-4), the lumbar splanchnic nerves or lumbar colonic nerves (LCN). The frequency of efferent discharges of LCN was increased slightly by rectal distension and remarkably increased after Th 13 and/or L 4 transection. Thus, there occurs during the recto-rectal reflex not only mucosal intrinsic reflex and sacral excitatory reflex via the pelvic nerves but also a lumbar inhibitory reflex via the colonic nerves, whose center may be located in the upper lumbar segments.But, the activity of the inhibitory center was depressed by the supraspinal center, so that an excitatory reflex is produced more dominantly than an inhibitory one in normal animals. All these extrinsic reflexes coordinate the activity of the myenteric plexus in defecation reflex.

Effects of capsaicin on myenteric neurons of the guinea pig ileum

The effects of capsaicin on the electrophysiological behavior of myenteric neurons were investigated with intracellular recording techniques in the isolated guinea pig ileum. Capsaicin evoked a marked long-lasting slow depolarization associated with increased input resistance, during which the cells spiked repeatedly or displayed anodal break excitation. Capsaicin did not produce the slow depolarizing action on myenteric neurons in Ca2(+)-free media (with 0.1 mM ethylenediaminetetraacetic acid) or in the mesenteric denervated ileum. This action of capsaicin on myenteric neurons seems to be mediated via a release of substance P, possibly from sensory nerve endings.

Effects of mesenteric nerve stimulation on the electrical activity of myenteric neurons in the guinea pig ileum

Effects of mesenteric nerve stimulation on the electrical activity of 28 myenteric neurons were investigated in the myenteric flaps innervated with mesenteric nerves. Mesenteric nerve stimulation evoked slow excitatory postsynaptic potentials (EPSPs), whose amplitude and duration were 24.5 +/- 5.5 mV and 374.6 +/- 58.9 s in 7 AH/Type 2 neurons, respectively. Such slow EPSPs mimic the slow depolarizing action induced by exogenous substance P. It is, therefore, likely that slow EPSPs might be in part mediated by the release of substance P.

Possible involvement of calcitonin gene-related peptide (CGRP) in non-cholinergic non-adrenergic relaxation induced by mesenteric nerve stimulation in guinea pig ileum

Mesenteric nerve (MN) stimulation produced a biphasic response, i.e., a contraction followed by a prolonged relaxation in the isolated guinea pig ileum after complete adrenergic neuron blockade with guanethidine. This biphasic response mimicked the effect of capsaicin by itself. The latter relaxation response to MN stimulation was unaffected by hexamethonium, but was abolished by capsaicin in an irreversible fashion. Calcitonin gene-related peptide desensitization (CGRP-D) reduced the relaxation response to about 20% of the control. After pretreatment with atropine and guanethidine, MN stimulation provoked a pure relaxation, which was significantly reduced to about 20% of the control by CGRP-D. Therefore, it seems likely that the non-adrenergic non-cholinergic relaxation response to MN stimulation is partly mediated via a release of CGRP from sensory nerve endings.

Pelvic afferent reflex control of rectal motility and lumbar colonic efferent discharge mediated by the pontine sympatho-inhibitory region in guinea pigs.

Rectal motility and the efferent discharge of lumbar colonic nerves (LCED) have previously been shown to be affected by reflex activity activated by rectal stimulation. The sensory limb of this reflex is represented by afferent fibers in pelvic nerves. The present study revealed that this reflex is modulated by supraspinal sympatho-inhibitory regions. Pelvic afferent stimulation led to rectal contraction through the withdrawal of a tonic inhibitory influence of lumbar colonic nerves. The supraspinal region responsible for this antagonism ofthe rectal-inhibitory colonic nerve activity was localized to the pons. Neither the intravenous administration of atropine nor that of guanethidine (and Eisai compound 865–123, another adrenergic neuron blocking agent) effected the ability of pelvic afferent stimulation to inhibit tonic discharge of lumbar colonic efferent nerves; nervertheless, both agents eliminated the mechanical response of the rectum to stimulation of pelvic afferents. These observations suggest that lumbar sympathetic nerves may tonically inhibit the release of acetylcholine from excitatory neurons in the rectal myenteric plexus. We conclude that descending fibers from the pons are activated as a result of pelvic afferent nerve stimulation. These descending pontine fibers in turn inhibit the firing of sympathetic lumbar colonic nerves. Removal of this tonic restraint leads to rectal contraction.

Role and localization of a region in the pons which has a descending inhibitory influence on sympathetically mediated inhibition of the recto-rectal reflex of guinea pigs

The present study revealed the site of origin and the possible function of a supraspinal descending-inhibitory influence over the lumbar sympathetic component of the recto-rectal reflex of guinea pigs. The recto-rectal reflex contraction was not changed by suprapontine transection. It completely disappeared after subpontine transection, but returned immediately after additional section of the colonic nerves, which contain the sympathetic inhibitory outflow to the rectum, i.e., subpontine transection with the lumbar colonic nerves transected did not suppress the recto-rectal reflex. These results indicate that a descending pathway which can inhibit the lumbar sympathetic component of the reflex may originate in the pons. On stimulation at sites within the pons of animals which had been spinalized at L4 we were able to evoke an increase of rectal motility and an inhibition of the lumbar colonic efferent discharges, thus producing a response which is comparable to the reflex response produced by afferent stimulation of the rectum.The sites from which this effect could be evoked were mainly located in a band running rostrocaudally through the lateral reticular formation of the rostral part of the pons, medial to the sensory nucleus of the trigeminal nerve.

Effects of neurotensin on the motility of the isolated gallbladder, bile duct and ampulla in guinea-pigs

Neurotensin induced dose-dependent contraction in the isolated gallbladder, bile duct and ampulla of guinea-pigs, which were usually reduced by atropine and tetrodotoxin. In all cases, the neurotensin-induced contraction of the gallbladder was reversed to relaxation by indomethacin after administration of atropine and tetrodotoxin. The neurotensin-induced contraction of bile duct and ampulla was reduced by indomethacin, atropine and tetrodotoxin, and was slightly enhanced in some experiments after guanethidine administration. Ganglion-, alpha- and beta-adrenoceptor, serotonin- and histamine-blocking agents did not affect the neurotensin-induced contraction in any of the preparations. These results suggest the following; (1) the contractile effects are due to excitement of cholinergic neurons in the myenteric plexus of the biliary tract, (2) the direct action of neurotensin on the smooth muscle of the bile duct and ampulla results in a small contraction, (3) the contraction in the gallbladder is partly caused by stimulation of prostaglandin synthesis.

Inhibitory effect of capsaicin on the ascending pathway of the guinea-pig ileum and antagonism of this effect by ruthenium red.

A segment of guinea-pig ileum, which was continuous with a strip of longitudinal muscle-myenteric plexus (LM-MP) at the anal end, was used to examine the effect of capsaicin on ascending excitatory pathways. Electrical field stimulation of the LM-MP caused an ascending contraction of the segment. After initially causing contraction capsaicin (3 microM) inhibited the ascending contraction. This inhibitory effect of capsaicin exhibited rapid desensitization and was abolished after extrinsic (mesenteric) denervation. Desensitization to calcitonin gene-related peptide (CGRP) prevented the capsaicin-induced inhibition without affecting the ascending contraction. Neither naloxone nor alpha- and beta-adrenoceptor antagonists affected the capsaicin-induced inhibition. CGRP (25 nM) also inhibited the ascending contraction, mimicking the inhibition induced by capsaicin. Ruthenium red (0.1-3 microM) antagonized the capsaicin-induced inhibition in a concentration-related manner, but did not affect the CGRP-induced inhibition. These findings suggest that the inhibitory effect of capsaicin on the ascending pathways might be mediated via the release of CGRP from extrinsic nerve terminals, and that the site of the antagonism of the action of capsaicin by ruthenium red is prejunctional.

Indomethacin-induced lesion modifies contractile activity in rat small intestines.

BACKGROUND Indomethacin induces intestinal lesions. The change in contractility of segments with lesions was studied. METHODS Motility was recorded in segments with lesions isolated from the rat small intestine 24 h after a subcutaneous injection of indomethacin (20 mg/kg). RESULTS Concentration-contraction curves for acetylcholine shifted leftward independently of the degree of severity of lesions, but the curves for carbachol and 5-hydroxytryptamine did not. Contractions produced by intramural nerve stimulation were enhanced in segments with no visible damage but decreased with progression of lesions. Neostigmine augmented them in normal rats but not in indomethacin-treated rats. The peristaltic activity was enhanced in segments with no visible lesions. CONCLUSIONS The results suggest that treatment of the rat with indomethacin enhances contractility of the small intestine owing to diminution of acetylcholinesterase activity independently of the degree of lesions and reduces it owing to decreased responsiveness of enteric neurons with the progression of lesions.

Capsaicin‐sensitive afferents activate a sympathetic intestinointestinal inhibitory reflex in dogs.

1. In urethane‐anaesthetized dogs, an intra‐arterial infusion of capsaicin (0.7‐14 nmol min‐1) into a separated jejunal segment inhibited a vagally evoked cholinergic contraction of the other non‐infused segments. The mechanism of this reflex was investigated. 2. The inhibition by capsaicin was abolished after bilateral splanchnic nerve section or cervical spinal cord transection (C5 or C6), but was unaffected by bilateral vagotomy. Decerebration partially reduced the inhibition. 3. The inhibition by capsaicin was abolished by pre‐treatment with phentolamine or yohimbine, but was unaffected by prazosin or propranolol. 4. Sympathetic efferent discharge of the mesenteric nerve increased with capsaicin application, during which time vagally evoked contractions were inhibited. 5. Single‐unit discharges of the major splanchnic and mesenteric afferents increased with capsaicin infusion to the loop which was innervated by the units. 6. Together the results implied that capsaicin stimulated canine intestinal primary afferents, resulting in the sympathetic intestinointestinal inhibitory reflex supraspinally. The inhibition of vagally evoked contractions may be due to a presynaptic inhibition via alpha 2‐adrenoceptors, which are activated by the reflex.