2000 Fiscal Year Final Research Report Summary
ROLES OF PROTEASE-ACTIVATED RECEPTORS IN THE ALIMENTARY SYSTEMS : PARTICIPATION IN THE MODULATION OF FUNCTIONS IN THE SALIVARY GLANDS, PANCREAS AND SMALL INTESTINE
| Project/Area Number |
11672283
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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 |
応用薬理学・医療系薬学
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| Research Institution | KINKI UNIVERSITY |
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Principal Investigator |
KAWABATA Atsufumi KINKI UNIVERSITY, DEPT.OF PATHOPHYSIOLOGY, FAC.OF PHARMCEUT.SCI, 薬学部, 助教授 (20177728)
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| Co-Investigator(Kenkyū-buntansha) |
KURODA Ryotaro KINKI UNIVERSITY, DEPT.OF PATHOPHYSIOLOGY, FAC.OF PHARMCEUT.SCI., PROFESSOR, 薬学部, 教授 (10161803)
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| Project Period (FY) |
1999 – 2000
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| Keywords | protease-activated receptor / protease / PAR / gastrointestinal motility / salivation / pancreatic secretion |
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| Research Abstract |
Protease-activated receptors (PARs), G protein-coupled seven trans-membrane domain receptors activated by certain proteases such as thrombin, trypsin and tryptase, play various physiological/pathophysiological roles especially during tissue injury or inflammation. We investigated the physiological roles of PARs in the alimentary systems.
Activation of PAR-1 produced apamin-sensitive relaxation followed by contraction in the isolated rat duodenal smooth muscle. PAR-2 activation elicited only contraction. PAR-4 produced no response. The PAR-1-mediated contraction was largely dependent on increased sodium permeability and activation of L-type calcium channels, and in part on activation of tyrosine kinase, protein kinase C and PI3 kinase.
We next detected mRNA for PAR-2 in the salivary glands and pancreas. Then, activation of PAR-2 in vivo markedly augmented exocrine secretion in both the tissues.
In conclusion, our study demonstrates that PARs present in the small intestine, salivary glands and pancreas modulate various physiological functions, predicting that PARs could be targets for drug development.
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