Teruhiro Yamasato

Role of 5‐HT3 receptors in peristaltic reflex elicited by stroking the mucosa in the canine jejunum.

1. 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 (1.0 g kg‐1, I.V.) and alpha‐chloralose (100 mg kg‐1, 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‐1 to 14 nmol min‐1 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‐1 for both). 4. The ascending contraction was markedly inhibited by treatment of either segment with hexamethonium (140 nmol min‐1). The response was abolished by treating both segments with hexamethonium and by treating the oral segment with atropine (14 nmol min‐1). 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.

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.

Histochemical study of the lumbar colonic nerve supply to the internal anal sphincter and its physiological role in dogs

The sympathetic innervation of the internal and sphincter (IAS) and its physiological role in maintaining sphincter tone were histochemically and mechanically studied in dogs anesthetized with pentobarbital sodium. Numerous catecholamine-fluorescent nerve fibers with varicosities were identified in the IAS of normal dogs. Such fibers were markedly reduced at one week and one month after resection of the hypogastric nerves (HGNs) or the lumbar colonic nerve (LCN), and disappeared after combined HGN and LCN resection. IAS tone decreased to 37.2% of baseline at 1 h after LCN resection and to 69.9% after HGN resection. It returned to the preoperative level at one week and one month after resection. The restored IAS tone was decreased again by acute transection of the previously intact HGNs or LCN. Combined LCN and HGN resection also caused a marked reduction of IAS tone (36.9%) at 1 h after the procedure, and was then restored to the preoperative level with time. The restored tone was not decreased by phentolamine administration. These findings confirmed that both the LCN and the HGN innervate the IAS and play a physiological role in the development of resting tone. The restoration of IAS tone after denervation may be due to intrinsic myogenic properties of the sphincter.

RELATIONSHIP BETWEEN ACTIVITIES OF THE SPHINCTER OF ODDI AND THE DUODENAL MUSCLE

To investigate the relationship between the activity of the sphincter of Oddi and that of the duodenal muscle, intracellular action potentials of them were recorded in the isolated preparation of the rabbit.The spontaneous rhythmic contraction of the sphincter of Oddi induced a retardation of the outflow of the perfusate through the common bile duct to the duodenal lumen, and when acetylcholine was administered there occurred tonic contraction which stopped the outflow of the perfusate.A burst of the spike potentials of the sphincter of Oddi was recorded synchronously to the longitudinal contraction of the duodenum (the pendular movements). The spike potentials in thelatter precede the former.Several hours after isolation of the preparation the sphincter of Oddi contracted independently of the longitudinal contraction of the entire duodenum. In such a case, a part of the duodenal muscle around the sphincter of Oddi discharged the spike potentials unsynchronously or synchronously to those in the latter.It is supposed from an anatomical structure and the facts described that there will be a functional connection between the sphincter of Oddi and the longitudinal muscle of the duodenum close to it.

EFFECT OF CAERULEIN ON THE INTESTINAL MOVEMENTS, ESPECIALLY ITS EFFECT THROUGH THE CENTRAL NERVOUS SYSTEM.

Theexcitatory effect induced by caerulein (5-20ng/kg, i. v.) on the movements of the denervated jejunal loop is more powerful than that on the innervated one. Using dogs anesthetized with pentobarbital sodium , i. v.), the mechanism of this phenomenon was studied. 1. On the innervated jejunum, the excitatory effect of caerulein was markedly increased after bilateral splanchnicotomy, the transection of spinal cord at the level of 5th cervical segment or decerebration between superior and inferior colliculi , whereas the effect was unchanged after bilateral vagotomy at the . 2. From the results obtained ,it was concluded that caerulein probably induced the excitation of sympathetic area in the brain cranial to the superior colliculus , which caused spinal sympathetic activation , resulting in inhibition of the intestinal motility through the splanchnic nerves , while caerulein caused the excitatory effect on the inteStinal motility through the excitatory myenteric neurones , as reported in the Previous paper.