Effects of caerulein on the gastric motility of rats.

The effects of caerulein on gastric motility in urethane-anesthetized rats were studied. Caerulein administered into the lateral cerebral ventricle (i.c.v.) and jugular vein (i.v.) caused predominantly an inhibitory effect on gastric motility but sometimes an excitatory or a biphasic effect. The inhibitory response was reduced after vagotomy and/or splanchnicotomy, or after guanethidine. The remaining inhibitory response was abolished by tetrodotoxin, but was resistant to atropine and guanethidine. The excitatory response was abolished by atropine. Discharges of the gastric branch of the vagus nerve were decreased by i.v. injection of caerulein but increased by i.c.v. injection, whereas those of the splanchnic nerve were increased by both i.v. and i.c.v. injection. These results suggest that caerulein causes an inhibition of gastric motility by centrally stimulating vagal non-adrenergic inhibitory nerves and splanchnic adrenergic nerves and inhibiting vagal cholinergic nerves, and by peripherally stimulating non-adrenergic inhibitory neurons of the myenteric plexus. This peptide causes an excitation by stimulating cholinergic neurons of the myenteric plexus.</p

The effect of cecal volume change on gastric motility in rats.

The effect of a change in cecal volume on gastric motility was studied in 24 h fasted rats anesthetized with urethane (0.8 g/kg, i.p.). A cecal volume increase from 1 to 10 ml (in 1 ml steps) produced a decrease in the basal tone of the stomach. The maximal inhibitory response was produced with an 8 to 10-ml increase in cecal volume. The gastric inhibitory response continued as long as the increased cecal volume was maintained. It was abolished by a combination of a splanchnicotomy and vagotomy, or only a splanchnicotomy in a few cases. The inhibition of gastric motility by increasing the cecal volume also occurred after severance of dorsal roots between T8 and L4 and gastric branches of vagus nerves. It is suggested that an increase in cecal volume induces gastric relaxation mainly via the splanchnico-splanchnic pathway and partly via the vago-vagal and vago-splanchnic pathways. Therefore, retardation in transit of the gastric contents in germ free rats having an enlarged cecum may be attributed to an enhancement of the ceco-gastric inhibitory reflex. The ceco-gastric inhibitory response mediated by the splanchnic pathway was abolished by guanethidine (3-5 mg/kg, i.v.), but the response mediated by the vagal pathway was resistant to guanethidine as well as to atropine (0.2 mg/kg, i.v.). This result indicates that splanchnic postganglionic efferents are adrenergic, while vagal postganglionic efferents are non-adrenergic and non-cholinergic.</p

Effect of motilin on the sphincter of Oddi in the dog.

To investigate the action of motilin on the sphincter of Oddi, the flow rate of the perfusate (FRP) discharged into the duodenal lumen through the orifice of the common bile duct was measured by means of an electric drop counter in decerebrated dogs. Motilin in doses above 0.5 micrograms/kg i.v. reduced or stopped the FRP. The fifty percent recovery time of FRP was 20 min and full recovery time was 30 min. The reduction of FRP induced by motilin was unaffected by denervation and atropinization. These results suggest that motilin caused an increase in tone of the sphincter of Oddi by acting on the sphincter muscle.</p

Antroduodenal coordinated contractions as studied by chemical ablation of myenteric neurons in the gastroduodenal junctional zone.

Antroduodenal contractions were studied in rat preparations. Augmented duodenal contractions occurred spontaneously in coordination with antral contractions in normal and saline-pretreated preparations. The coordination did not occur when muscle layers and the myenteric plexus were transversely cut at the duodenum just anal to the gastroduodenal junction. In silent preparations, the coordinated contractions were produced by neostigmine or domperidone. When the antroduodenal junctional zone was pretreated with benzalkonium chloride, the augmented duodenal contractions did not occur spontaneously, and even after administration of neostigmine and domperidone although antral contractions occurred spontaneously. In these preparations, there were notably few myenteric neurons in the junctional zone, but the neurons were distributed normally in the areas where motility was recorded. The results suggest that myenteric neurons mediate antroduodenal coordinated contractions and that the coordination is modified by myenteric cholinergic excitatory and dopaminergic inhibitory pathways.</p

The effect of intraluminal pressure upon the frequency of intestinal contraction waves.

In guinea pigs the lumen of an excised jejunal segment was perfused to study the effect of intraluminal pressure on the frequency of rhythmic contraction waves. Within the range of 0 to 40 mmH2O, increases in intraluminal pressure caused increases in the frequency of contraction waves. At pressures of 10, 15, 20, 30 and 40 mmH2O the frequency was 7.9, 9.0, 10.9, 12.5 and 13.3 per min (mean of ten preparations), respectively. An exponential relationship was proved to exist between the pressure and the frequency.</p

Effects of vagotomy on feeding and defecation in guinea pigs.

The effect of subdiaphragmatic vagotomy on food intake and defecation was studied in guinea pigs. Weights of food and feces were measured for at least three weeks after vagotomy. The weight of daily food intake and feces evacuated increased about 15 and 30% after vagotomy compared with controls whereas it did not change in sham operated animals. The weight of scybalum decreased after vagotomy although the number increased markedly. It was considered that an increase in food intake after vagotomy may result from blocking of satiety signals mediated by the vagus; moreover, that the increase in feces may depend on the enhancement of scybalum formation in the proximal colon resulting from increasing food intake and transportation of the larger amount of the contents after vagotomy.</p

Functional role of lumbar sympathetic nerves and supraspinal mechanism in the defecation reflex of the cat.

The role of the lumbar sympathetic nerves and supraspinal mechanism in the defecation reflex was investigated in 30 adult cats and 6 kittens. One or two propulsive contractions, whose mean pressure evoked was more than about 90 cmH2O (adult cats) and 50 cmH2O (kittens), were induced in the rectum of all animals by rectal distension. These propulsive contractions could be generated at the descending and the transverse colons. The removal of the supraspinal influence by spinal transection at T13 or removal of pelvic afferents to the supraspinal center by spinal transection at L abolished the propulsive contractions. Successive lumbar sympathectomy restored the contractions. Lumbar sympathectomy and the successive removal of the supraspinal influence did not affect the propulsive contractions. In both cases, the final exclusion of the sacral segments by pithing of the spinal cord abolished the propulsive contractions. These results suggest that the sacral excitatory reflex mediated via pelvic nerves and the lumbar inhibitory reflex mediated via lumbar sympathetic nerves can function during rectal distension in spinal cats and that the lumbar inhibitory reflex is suppressed by the supraspinal sympathetic inhibitory reflex activated by pelvic afferents in intact cats, as in guinea pigs, resulting in propulsive contractions.</p

Atropine-sensitive, tetrodotoxin-resistant contraction induced by noradrenaline in isolated cat rectum.

Effects of noradrenaline (NA) on the isolated rectal circular muscle of the cats were studied in comparison with the effects on the internal anal sphincter (IAS). NA (10(-8)-10(-7) g/ml) caused tonic contraction in four of 15 strips of the rectum taken from 15 animals, and in all 15 strips of the IAS. Phenylephrine also induced rectal and IAS contraction. Rectal contraction induced by NA was resistant to phentolamine, yohimbine, propranolol, hexamethonium and tetrodotoxin, but blocked by atropine. IAS contraction induced by NA was resistant to propranolol, atropine, hexamethonium and tetrodotoxin, but blocked by phentolamine and yohimbine. It is suggested that an atropine-sensitive excitatory adrenergic mechanism other than the excitatory alpha-adrenergic mechanism exists in the rectal circular muscle.</p

Mechanism of rectal contraction mediated by sympathetic efferents from rectoanal pelvic afferents in guinea pigs.

In guinea pigs whose pelvic nerves were bilaterally sectioned, afferent stimulation of rectoanal branches of the pelvic nerve (PAS) could produce an intense contraction in the rectum similar to propulsive contractions elicited during defecation. The mechanism of this reflex was analyzed. Rectal contraction by PAS was abolished after transecting the spinal cord at T13 or sectioning the lumbar splanchnic nerves (LSN) or lumbar colonic nerves (LCN), but was unaffected by severing the intermesenteric and hypogastric nerves. Rectal contraction induced by PAS was abolished peripherally by atropine, guanethidine or yohimbine, while propranolol had no affect. Yohimbine antagonized the inhibitory effect of LSN or LCN stimulation on atropine-sensitive rectal contractions. It may, therefore, be concluded that PAS blocks the inhibition, by LCN efferents acting through alpha-adrenoreceptors, of cholinergic neurons in the myenteric plexus, thus facilitating recto-rectal propulsive contractions initiated by the defecation reflex.</p

Intrinsic reflexes mediated via peptidergic neurons in the smooth muscle esophagus of the hen.

In the extrinsically denervated smooth muscle esophagus of the hen anesthetized with urethane (1 g/kg, i. m.), it was studied whether peptidergic neurons in the intramural plexus are involved in the intrinsic reflex. Ascending and descending contractions, and descending relaxation were induced by electrical stimulation of a narrow segment of the esophagus. Naloxone (1 microM), desensitization to substance P (0.3 microM) and spantide (20 microM) inhibited the ascending and descending contractions, respectively. The degree of the inhibition of the contractile response by a combination of naloxone and substance P was nearly the same as that by a single administration of naloxone or substance P. The ascending and descending contractions were reduced to one-third of the control by hexamethonium (100 microM) and abolished by atropine (10 microM). The descending relaxation was abolished after desensitization to vasoactive intestinal peptide (0.3 microM). Taken together the results suggest that in the hen's esophagus, opioid- and substance P-containing neurons in the intramural plexus may act as preganglionic neurons of cholinergic motor neurons in the ascending and descending excitatory pathways and that vasoactive intestinal peptide-containing neurons are involved in the descending inhibitory pathway.</p