Role of PGE_2 and PGI_2 in Gastric Neural Emergency System
| Project/Area Number |
13672396
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
応用薬理学・医療系薬学
|
|---|
| Research Institution | Kitasato University |
|---|
Principal Investigator |
HAYASHI Hiromi Kitasato Univ. School of Medicine Research Associate, 医学部, 助手 (20238124)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MAJIMA Masataka Kitasato Univ. School of Medicine Professor, 医学部, 教授 (70181641)
ARAI Katsuharu Kitasato Univ. School of Medicine Research Associate, 医学部, 助手 (50286259)
SAEKI Takeo Kitasato Univ. School of Medicine Research Associate, 医学部, 助手 (20265614)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Project Status |
Completed (Fiscal Year 2002)
|
| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
|
|---|
| Keywords | neural emergency system / capsaicin / CGRP / gastric mucosal injury / prostaglandin I_2 / IP receptor knockout mice / PGI2 / 胃粘膜微小循環 / エタノール胃粘膜傷害 / EPレセプターノックアウトマウス / PGE2 |
|---|
| Research Abstract |
Background: Administration of capsaicin also inhibited ethanol-induced gastric mucosal injury through the immediate release of calcitonin gene-related peptide (CGRP) from primary sensory neurons, which is called the neural emergency system. In the present study, we tested whether endogenous prostaglandin I2 also modulates cytoprotective action by capsaicin using IP knockout mice.
Methods: The stomachs of prostaglandin I receptor knockout mice (IP-/-) or their wild-type mice (IP+/+), anesthetized with urethane (1.225 g/kg, ip), were doubly cannulated from the esophageal and duodenal sides, and the gastric mucosa was perfused (0.5 ml/min) with physiological saline. Perfusate was estimated at the end of each perfusion experiment. In some animals, CGRP-(8-37), a CGRP antagonist (3 mg/kg) or indomethacin 81 mg/kg) was intravenously injected before perfusion of 50% ethanol containing capsaicin.
Results: Capsaicin inhibited injured area in a dose dependent manner. Fifty % ethanol containing cap
… More
saicin (480 μM) immediately increased intra-gastric levels of CGRP, although 50% ethanol alone did not. The protective action of capsaicin (480 μM) against ethanol was completely abolished by intravenous injection of CGRP-(8-37). Indomethacin also inhibited the protective action of capsaicin, and this was accompanied with reduced levels of intra-gastric CGRP. Intra-gastric levels in prostaglandin E_2 were not increased by capsaicin treatment, but those in 6-keto-prostagalandin F1α, a metabolite of prostaglandin I_2, were markedly increased. No protective action of capsaicin was observed in IP-/-, which lacked the ability to increase intragastric CGRP levels in response to ethanol containing capsaicin. The CGRP content of the stomach from untreated IP-/- did not differ from those in IP+/+.
Conclusions: The present results suggest that endogenous prostaglandin I_2 enhances the protective action of the capsaicin-mediated neural emergency system against ethanol-induced gastric mucosal injury through the enhancement of CGRP release. Less
|
Report
(3 results)
Research Products
(13 results)
