THE VAGAL INHIBITORY RESPONSES OF THE STOMACH TO STIMULATION OF THE DOG'S MEDULLA OBLONGATA

Transcription

1 Japanese Journal Physiology 14, pp , 1964 THE VAGAL INHIBITORY RESPONSES OF THE STOMACH TO STIMULATION OF THE DOG'S MEDULLA OBLONGATA Takehiko SEMBA, Kazumoto FUJII AND Nobumasa KIMURA * Department Physiology, University Hiroshima Medical School, Hiroshima present authors have demonstrated on previous work21) that stimulation dorsal nuclei vagus produced motor response stomach through splanchnic nerve as well as through vagus nerve. This fact suggests us that stimulation gastric inhibitory center3) in medulla oblongata will produce inhibition stomach through vagus nerve as well as through splanchnic nerve. Although it is considered that vagus nerve contains only motor nerve to stomach7,8), it has been reported by many investigators that stimulation vagal nerve trunk produced inhibitory responses to gastro-intestinal tract ( literatures are shown in LANGLEY11), CARLSON et al.2), and M'CREA et al.14)). And it was considered that reversed effects vagus nerve were dependent on peripheral factors in stomach and small intestine1,4,8), and also on conditions stimulation1, 4, 18). However, mechanism reversed effects vagus nerve has not yet been determined8). present study was undertaken by stimulating medulla oblongata in order to demonstrate vagal inhibitory effects on stomach movements. METHODS Dogs (weight 5-12 kg) were used in all experiments. animal was fasted for hours before surgical operation, and anestized with intravenous injection Nembutal (Abbott Co. 25 mg/kg body weight). animal was held in ventricumbent position. portion cisterna cerebello-medullaris was excised to observe dorsal surface caudal portion forth ventricle and obex. systemic blood pressure was measured at common carotid artery with mercury manometer, and movements antrum and pyloric portion -stomach were reco rded on kymograph by balloon tambour system. Received for publication May 16,

2 320 T. SEMBA, K. FUJII AND N. KIMURA electronic stimulator (Nihon-Kohden Co. MSE-3) was employed with an intensity 1-4 V, frequency c/s, duration 0.6 msec. and period seconds. mono-polar tungsten electrode (enameled with exception tip) was microns in diameter. Two cm ~4 cm silver plate was used as an indifferent electrode and applied under skin neck region. When inhibitory responses stomach were obtained as a result stimulation, weak direct current (0.2 ma, 1.5 V) was applied for a few seconds before position stimulating electrode was changed, to rmally coagulated stimulated area. Thus position electrode was determined in future histological examination. After end physiological experiments, animal was sacrificed by bleeding. medulla oblongata was removed, and fixed in 10% formalin solution. After paraffin embedding, serial coronal sections were prepared at 30 microns thick. Four pieces serial sections were stained by Kluver & Barrera method, and next one was stained by Nissl method alternatively. In this manner, two stainings preparations could be examined microscopically on its nerve fibers and cells. RESULTS 1) typical vagal inhibitory effect caused by stimulation medulla oblongata was shown in FIG. 1A. spinal cord was previously transected between cervical and thoracic region in order to avoid effects excitation spinal sympatic nerves. medulla oblongata was stimulated at 1 mm to left dorsal median sulcus and 2 mm deep at level oral side alae cinerea. No changes eir on systemic blood pressure (82 mmhg) or on respiratory excursions were observed, but tone skeletal muscles in neck region was increased during stimulation. movements stomach were inhibited completely. peristaltic movements (6 contractions per minute) were completely arrested, tone stomach diminished, after a few second latency. inhibitory effects stomach were maintained 2 minutes after end stimulation. On same animal, stimulation central portion right alae cinerea 1 mm deep, produced marked increase gastric tone and peristalsis and bradycardia. After successive severances bilateral vagus nerves in cervical region same animal, stimulation almost same area which used to produce inhibitory response, caused no changes in movements and tone stomach as shown in FIG. 1B. According to histological examination, stimulated area which produced inhibitory effects was located in medial longitudinal fascicle as shown in FIG. 1C, and motor area was found in dorsal nuclei vagus,

3 VAGAL GASTRIC 321 INHIBITION A B FIG. 1A: vagal inhibitory effects caused by stimulation medulla oblongata. spinal cord was severed between cervical and thoracic cord. vagus nerves were intact. B: After bilateral vagotomy, same area was stimulated. description curves is from top downwards; systemic blood pressure, movement stomach, signal and time marks (6 secs.). FIG. in FIG. cinerea. ª 1C: 1A. location coronal stimulated section area, stimulated through Kluver-Barrera area level on stain 6 ~. example oral side shown alae

4 T. SEMBA. 322 K. FUTII AND N. KIMURA A FIG. 2A: medulla thoracic cord. vagal oblongata. FIG. FIG. cinerea. ª inhibitory Spinal vagus effect was abolished same area was as shown in FIG. 1. in B nerves after stimulated. 2C: location 2A. coronal section stimulated area effect cord was were intact. caused by severed B: stimulation cervical and between vagal application hexamethonium description curves stimulated through Kluver-Barrera area stain on level 6 ~. inhibitory bromide. is same example 3/4 shown oral alae

5 VAGAL GASTRIC INHIBITION 323 2) example shown in FIG. 2A, spinal cord was also transected at level between cervical and thoracic region. medulla oblongata was stimulated at 1 mm to right dorsal median sulcus at level 3/4 oral alae cinerea. electrode was applied 0.5 mm deep from dorsal surface. No changes eir on systemic blood pressure (85 mmhg) or on respiratory excursions were observed. tone skeletal muscles in neck region was increased slightly. peristaltic movements stomach were abolished after 20 seconds latency, and inhibitory response was maintained during stimulation. tone stomach was also diminished. On same animal, 15 minutes after application intravenous injection hexamethonium bromide (25 mg, Yamanouchi Co.), almost same area was stimulated. result was shown in FIG. 2B. Any influences to stomach movements and its tone were not observed. stimulated area was examined histologically and located in medial longitudinal fascicle as shown in FIG. 2C. 3) 46 dogs were used for this experiments and 38 inhibitory responses were observed in 29 dogs. distribution areas which produced vagal inhibitory responses stomach is plotted as solid circles in diagram as shown in FIG. 3. Twenty five inhibitory areas are located in medial longitudinal fascicle, 6 areas in reticular formation, 3 areas in raphes FIG. 3: Diagram shows coronal section through level oral side alae cinerea. Solid circles show inhibitory areas through vagus nerve.

6 324 T. SEMBA, K. FUJII AND N. KIMURA and one in each accessory cuneate nuclei, solitary fascicle, inferior vestibular nuclei and rubro-spinal tract. DISCUSSION 1. inhibitory response stomach was observed by stimulation medulla oblongata on dog which previously had bilateral splanchnic nerves severed and bilateral suprarenal glands removed3). However, increase systemic blood pressure was unavoidable in se examples, as result excitation spinal sympatic nervous system. In present experiments, spinal cord was previously transected, and so inhibition stomach movements was obtained without any changes systemic blood pressure (see FIG. 1A & 2A), and inhibitory response was abolished after bilateral vagotomy (see FIG. 1B). stimulation alae cinerea, i. e. dorsal nuclei vagus7,21), constantly produced motor response stomach on same example which produced inhibitory response. That is to say, motor and inhibitory responses stomach through vagus nerve were obtained on same animal. Many investigators studied about conditions which produced reversal vagus action on stomach, and considered that y were dependent on state tone stomach1,2,12,14), on blood supplies to stomach (anoxaemia4)) and on influence anessia4). However, it seems that above fact shows existence two kinds nerve fibers (motor & inhibitory) in vagus. It is already suggested by MAY13) and KURE et al.9) that vagus supplies to stomach with a great number sympatic fibers. 2. LANGLEY11) observed after injection atropine into a vein, an abrupt cessation strong peristalsis by stimulation vagus, and MCSWINEY & ROBSON15) reported that vagal inhibitory response was produced on isolated gastric smooth muscle on addition atropine. In present experiments, inhibitory response stomach was abolished completely after application hexamethonium bromide as shown in FIG. 2B. NAKAYAMA17) also demonstrated same phenomenon on small intestine, and he thought about existence inhibitory preganglionic fibers in vagus nerve. studies on cardio-accelerator nerve in vagus also support our results. SHIZUME23), NAITO16) and KATO et al.6) demonstrated that vagus nerve to heart contained both adrenergic and cholinergic fibers. 3. It was already reported by THOMAS, CRIDER & MOGAN24), LALICH, MEEK & HERRIN10) and YOUMANS25) that one efferent nerve pathways on ileo-gastric inhibitory reflex, was vagus nerve. IRISAWA5) and SEMBA19)

7 VAGAL GASTRIC INHIBITION 325 reported same phenomenon on vesico-gastric inhibitory reflex and SEMBA et al.20) also reported it on colon-gastric inhibitory reflex. se facts show us that vagal nerve plays a role to inhibit stomach movements not in abnormal conditions, but in physiological circumstances. 4. As results histological examination, a large number inhibitory areas were located in medial longitudinal fascicle as shown in FIG. 3. medial longitudinal fascicle is thought as an extrapyramidal tract which originates in midbrain and descends to spinal cord. Investigation connection between medial longitudinal fascicle and vagus nerve is future problems. However, DATE3) demonstrated that inhibitory centers stomach movements in medulla oblongata were located in solitary fascicle and its surroundings. And so it may be supported that inhibitory fibers run to solitary fascicle from medial longitudinal fascicle and connect with vagus nerve. One present authors expect close relationships between extrapyramidal tract and autonomic nervous system on experiments higher brain stem22). CONCLUSION inhibitory response stomach movements was investigated on dog which spinal cord was previously transected. 1. inhibitory response stomach movements was obtained through vagus nerve by stimulation medulla oblongata at 1 mm lateral to dorsal median sulcus, mm in depth from dorsal surface at level between central alae cinerea and its oral side. On contrary, stimulation alae cinerea (dorsal nuclei vagus) constantly produced motor response stomach movements same animal which inhibitory response had been observed. 2. vagal inhibitory response was abolished by bilateral vagotomy and also after application hexamethonium bromide. 3. A large number inhibitory areas was found in medial longitudinal fascicle. 4. It may be concluded from this experiment that adrenergic nerve fibers which inhibit stomach movements are contained in vagus nerve. This work was supported by grant Waksman Foundation Japan INC.

8 326 T. SEMBA, K. FUJII AND N. KIMURA REFERENCES 1) BROWN, G. L. AND GARRY, R. C. Reversal gastric vagus. J, Physiol., 175: 213, ) CARLSON, A. J., BOYD, T. E. AND PEARCY, J. F. innervation cardia and lower end oesophagus in mammals. Amer. J. Physiol. 61: 14, ) DATE, T. On localization center inhibitory response stomach in dog's medulla oblongata. (in Jap.) J. Hiroshima Med. Ass. 13 Orig. Ser. 13: 867, ) HUKUHARA, T., OKADA, H. AND YAMAGAMI, M. A factor conditioning inhibitory response intestinal motility to peripheral stimulation cervical vagus nerves. Acta Med. Okayama 11: 103, ) IRISAWA, Y. pressure reflexes from urinary bladder. (in Jap.) J. Physiol. Soc. Jap. 17: 420, ) KATO, G., ITO, S. AND OMI, I. Fibre analysis cardiac vagus nerve. Jap. J. Physiol. 8: 67, ) KOSAKA, K. AND YAGITA, K. Experimentelle Untersuchungen ilber den Ursprung des Nervus Vagus. Mitt. Med. Ges. Okayama 17: 187, 1, ) KUNTZ, A. Autonomic nervous system. 4 Ed. p. 227, 1953, Lea & Febiger, Philadelphia. 9) KuRf:, K., ICHIKO, K. AND ISHIKAWA, K. On spinal parasympatic. Physiological significance spinal parasympatic system in relation to digestive tract. Quart. J. exp. Physiol. 21: 1, ) LALICH, J., MEEK, W. J. AND HERRIN, R. C. Reflex pathways concerned in inhibition hunger contractions by intestinal distention. Amer. J. Physiol. 115: 410, ) LANGLEY, J. N. On inhibitory fibers in vagus for end oesophagus and stomach. J. Physiol. 23: 407, ) LAUGHTON, N. B. effects on stomach stimulation dorsal vagus nuclei. Amer. J. Physiol. 89: 18, ) MAY, W. P. innervation sphincters and musculature stomach. J. Physiol. 31: 260, ) M'CREA, E. D., M'SWINEY, B. A. AND STOPFORD, J. S. B. effect on stomach stimulation peripheral end vagus nerve. Quart. J. exp. Physiol. 15: 201, ) MCSWINEY, B. A. AND ROBSON, J. M. response smooth muscle to stimulation vagus nerve. J. Physiol. 68: 124, ) NAITO, H. Studies on cardiac parasympatic function. efferent parasympatic cardio-accelerator nerve. (in Jay.) J. Kansai Med. Sch., 9: 59, ) NAKAYAMA, S. inhibitory nerve fibers to small intestine in vagus nerve. (in :Tap.) T. Physiol. Soc. Jap. 24: 368, ) ROGERS, F. T. AND BERCOVITZ, Z. A note on role intrinsic plexus in determining effects on gastric motility vagus stimulation. Amer. J. Physiol. 56: 257, ) SEMBA, T. motor response stomach and small intestine to stimulation urinary bladder. lap. J. Physiol. 6: 294, ) SEMBA, T., SASAKI, H. AND OKAMOTO, M. Reflex inhibition and excitation stomach caused by stimulation colon. (in Jap.) J. Phyiol. Soc. Jap. 19: 438, 1957.

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