2013 Fiscal Year Annual Research Report
炎症時に涙腺組織内で上昇するプロテアーゼは涙液分泌を促進するか？
| Project/Area Number |
23592585
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| Research Institution | Iwate Medical University |
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Principal Investigator |
木村 桂 岩手医科大学, 医学部, 講師 (10364358)
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| Co-Investigator(Kenkyū-buntansha) |
齋野 朝幸 岩手医科大学, 医学部, 教授(Professor) (40305991)
佐藤 洋一 岩手医科大学, 医学部, 教授(Professor) (40118253)
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| Keywords | 涙腺 / プロテアーゼ活性化型受容体 / 細胞内カルシウムイオン / 共焦点レーザー顕微鏡 / RT-PCR |
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| Research Abstract |
Protease-activated receptors (PARs) represent a novel class of seven transmembrane domain G-protein coupled receptors, which are activated by proteolytic cleavage. PARs have been prominently implicated in the regulation of a number of vital functions. Here, lacrimal gland acinar cell responses to PAR activation were examined, with special reference to intracellular Ca2+ concentration ([Ca2+]i) dynamics. In the present study, only PAR2 mRNA was detected by RT-PCR. Both trypsin and a PAR2-activating peptide (PAR2-AP) induced an increase in [Ca2+]i in acinar cells. The removal of extracellular Ca2+ and the use of Ca2+ channel blockers did not inhibit PAR2-AP induced [Ca2+]i increases. Furthermore, U73122 and xestospongin C failed to inhibit PAR2-induced increases in [Ca2+]i. The origin of the calcium influx observed after activated PAR2-induced Ca2+ release from intracellular Ca2+ stores was also evaluated. The NO donor mimicked the effects of PAR2 in activating non-capacitative calcium entry (NCCE). However, both calyculin A and a low concentration of Gd3+ did not completely block the PAR2-AP-induced increase in [Ca2+]i. These findings indicated that PAR2 activation resulted primarily in Ca2+ mobilization from intracellular Ca2+ stores and that PAR2-mediated [Ca2+]i changes were mainly independent of IP3. We suggest that PAR2-AP differentially regulates both NCCE and CCE, predominantly NCCE. Finally, our results suggested that PAR2 may function as a key receptor in calcium-related cell homeostasis under pathophysiological conditions such as tissue injury or inflammation.
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