2001 Fiscal Year Final Research Report Summary
In vivo analysis of regulatory mechanism of gastrointestinal motility
| Project/Area Number |
12670091
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Department of Pharmacology, Nagasaki University School of Medicine |
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Principal Investigator |
TANIYAMA Kohtaro Nagasaki University School of Medicine, Professor, 医学部, 教授 (70030898)
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| Co-Investigator(Kenkyū-buntansha) |
KAIBARA Muneshige Nagasaki University School of Medicine, Professor, 医学部, 助教授 (40274633)
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| Project Period (FY) |
2000 – 2001
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| Keywords | sympathetic neuron / Parasympathetic neuron / 5-Hydroxytryptamine (Serotonin) / GABA / Gastrointestinal motility / Acetylcholine / in vivo microdialysis |
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| Research Abstract |
To analyze relation of motor activity of the gastrointestinal tract with neuronal activity, the intestinal motility associated with acetylcholine (ACh) release was studied in the whole body of animals by determining simultaneously motor activity and ACh release with the in vivo microdialysis method, A dialysis probe was inserted into the wall of intestine at the site of the transducer sutured to the serosa for recording the mechanical response.
1. We established a new method to identify physiological intestinal motor activity associated with mainly the activity of cholinergic neurons in the whole body of animals. The cholinergic neuronal activity is regulated by adrenergic neurons and the local negative feedback system via muscarinic autoreceptors. These findings may lead to development of substance possessing antagonistic property of muscarinic autoreceptor as a prokinetics, such as Z-338.
2. 5-Hydroxytryptamine (5-HT) accelerates intestinal motor activity and increases the ACh release
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via 5-HT4 receptor. Prokinetics, mosapride also accelerates intestinal motor activity and the ACh release via 5-HT4 receptor. In vitro receptor autoradiography revealed that 5-HT4 receptor was located on the myenteric and submucosal plexuses and muscle layers of dog ileum and mosapride bound to 5-HT4 receptor. Thus, mosapride as well as 5-HT accelerates the intestinal motor activity due to the increase in ACh release mediated by stimulation of the 5-HT4 receptor.
3. γ-aminobutyric acid (GABA) inhibits the motor activity in parallel with decrease in the ACh release. A GABA_A agonist accelerated the motor activity and increased the ACh release, while A GABA_B agonist inhibits the motor activity and decreased the ACh release. Thus, GABA controls intestinal motor activity mainly via GABA_B receptor. With the in vivo microdialysis method, one can analyze mechanisms of endogenous bioactive substances underlying physiological and pathophysiological motor activity of the gastrointestinal tract, and drugs to treat subjects with gastrointestinal disorders can be developed. Less
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