No abstract

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 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.

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.

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 of the 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; nevertheless, 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.

SUMMARY1. The role played by the 5-HT3 receptor, a serotonin subtype receptor, in peristaltic reflexes was studied in dogs first given ketamine, then anaesthetized with urethane (10 g kg-', i.v.) and a-chloralose (100 mg kg-', i.v.). The jejunal loop was partitioned into two segments with respect to blood supply. Drugs were infused intra-arterially into each segment.2. Stroking of the mucosa of the aboral and oral segments elicited an ascending contraction and a descending relaxation, respectively.3. The ascending contraction was concentration-dependently inhibited by treatment of the aboral segment with the 5-HT3 receptor antagonists ICS 205-930 and ondansetron (1-4 pmol min-' to 14 nmol min-' for both). The maximal inhibition was 49*5 and 69-3 %, respectively. The response was not affected by treatment of the oral segment with these drugs. The descending relaxation was inhibited by 51-4 and 60-8 %, respectively, by treatment of the oral segment with ICS 205-930 and ondansetron (1-4 nmol min-' for both).4. The ascending contraction was markedly inhibited by treatment of either segment with hexamethonium (140 nmol min-'). The response was abolished by treating both segments with hexamethonium and by treating the oral segment with atropine (14 nmol min-').5. These results suggest firstly that, in the canine jejunum, enteric neurons with 5-HT3 receptors play a role as sensory neurons or interneurons in the ascending excitatory and the descending inhibitory pathways of the peristaltic reflex elicited by stroking the mucosa, and secondly, that the ascending limb is composed of cholinergic interneurons and motoneurons.

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We investigated the mechanism of ascending contraction induced by activation of 5-hydroxytryptamine3 (5-HT3) receptors in anesthetized dogs. Pressure-measuring balloons were inserted into a loop of extrinsically denervated jejunum. Drugs were administered via the arterial tree to the oral or the anal segment and the ensuing mechanical responses were monitored. Administration of 2-methyl-5-HT (440 pmol-44 nmol) to the anal segment caused contractions in the oral segment in a dose-dependent manner. This response was inhibited by treating the anal segment with ICS 205-930, cocaine, hexamethonium, or tetrodotoxin and by treating the oral segment with atropine or hexamethonium. The response persisted even after abolition of contraction in the anal segment by nifedipine. These results imply that activation of 5-HT3 receptors can induce an ascending contraction through an enteric excitatory pathway formed by a series of cholinergic interneurons and final cholinergic motor neurons, apart from the anal contraction.

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.