Project/Area Number |
07557315
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 試験 |
Research Field |
応用薬理学・医療系薬学
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Research Institution | Kochi Medical School |
Principal Investigator |
OSUMI Yoshitsugu Kochi Medical School, Pharmacology, Professor, 医学部, 教授 (80025634)
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Co-Investigator(Kenkyū-buntansha) |
SANO Shuichi Kochi Medical School, Internal Medicine I,Research Associate, 医学部, 助手 (50274379)
OKUMA Yasunobu Kochi Medical School, Pharmacology, Research Associate, 医学部, 助手 (20127939)
YOKOTANI Kumihiko Kochi Medical School, Pharmacology, Associate Professor, 医学部, 助教授 (30174858)
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Project Period (FY) |
1995 – 1996
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Project Status |
Completed (Fiscal Year 1996)
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Budget Amount *help |
¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1996: ¥500,000 (Direct Cost: ¥500,000)
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Keywords | Glutamic acid / Noradrenaline / Acetylcholine / Gastric function / Evaluation method of drug action / Vascularly-perfused gastric preparation / β-エンドルフィン / 神経伝達物質 / カルシウムチャネル / アミノ酸 |
Research Abstract |
We have developed experimental in vitro model to detect a very small amount of endogenous noradrenaline (NA) released from the rat gastric sympathetic nerves (Yokotani, K.et al., J.Pharmacol.exp.Ther., 1992). Then, in the present study, we further tried to establish practical availability of this model to elucidate precise mechanism of various gastric disorders and to develope their therapeutics. The isolated rat stomach was perfused with Krebs-Ringer solution (gastric artery*stomach*portal vein). Endogenous NA,acetylcholine (ACh) or glutamate (Glu) released into the perfusate was assayd by electrochmical or bioluminescence method. Results obtained were as follows. 1.Both high KCl and electrical stimulation of the vagus nerve induced a calcium dependent release of Glu. This release was abolished by tetrodotoxin. These results provide an evidence that Glu serves as a neurotransmitter in the stomach. 2.Electrical stimulation of the gastric sympathetic nerve induced a calcium dependent release of NA.Then, effects of various calcium chennel blockers selective to L,T,N,P,Q and R-type channels on this NA release were examined. N-type channel blockers alone but not others are effective to abolish the release. 3.Electrical stimulation of the vagus nerve induced a release of ACh. This release was blocked by a mu receptor agonist, beta-endorphin, while both of xi and chi receptor agonist was without effect. These results suggest that untoward effects of narcotic analgesics on the stomach probably originates from not only central but also direct action to the stomach. {Conclusion} : The isolated vascularly perfused rat stomach is probably a useful experimental model for various pharmacological studies of the stomach.
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