| Co-Investigator(Kenkyū-buntansha) |
DOHI toshihiro Hiroshima University, Faculty of Dentistry, Professor, 歯学部, 教授 (00034182)
KITAYAMA Shigeo Hiroshima University, Faculty of Dentistry, Associate Professor, 歯学部, 助教授 (80177873)
MORITA Katsuya Hiroshima University, Faculty of Dentistry, Assistant Professor, 歯学部, 講師 (10116684)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Research Abstract |
Methionine -enkephakin(Met-Enk) has been known to be co-released with catecholamine(CA) from adrenal medullary chromaffin cells when stimulated via nicotinic acetylcholine(Ach) receptor. The physiological role of released Met-Enk from adrenal gland, however, has not been clarified yet.
In this study, it was found that a long time exposure (6 to 24 hrs) of bovine adrenal medullary chromaffin cells to nicotine (10μM) induced a continuous release of Met-Enk, although CA release was transient. A newly-identified putative endogenous secretagogue, pituitary adenylate cyclase-activating polypeptide (PACAP, 10nM) evoked a long-lasting secretion of CA and Met-Enk. The CA content in chromaffin cells was not decreased after long-term Ach treatment, but even increased by PACAP. PACAP-induced CA release required extracellular CaィイD12+ィエD1 but was not inhibited by voltage-operated CaィイD12+ィエD1 channel blockers, A-kinase inhibitors, nor C-kinase inhibitor.
The effects of various opioid agonists on CA r
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elease in chromaffin cells were also investigated. Though Met-Enk is a μ-, and δ-agonists of these subtypes did not affect CA release. In contrast, κ-agonists like Dynorphin A(1-13) significantly reduced Ach-induced CA release. This inhibition was not antagonized by neither κ-specific nor non-specific opioid antagonists. Dynorphin A(1-13) also inhibited Ach-induced intracellular CaィイD12+ィエD1 concentration rise in chromaffin cells. Both dynorphin analogs, A(1-8) and A(2-13), which have been found to have less or no activity on κ-receptor, showed similar effects to A(1-13). In contrast, high KィイD1+ィエD1- nor PACAP-induced CA release was not affected by opioids. These results suggests that CA release from adrenal chromaffin cells is not autoregulated with Met-Enk, but may be regulated by another system involving dynorphin, thus κ subtype of opioids are plays different roles from μ or δ subtypes. Ach makes transient release of CA, while PACAP are supposed to be responsible for successive long-lasting release of CA, while PACAP are supposed to be responsible for successive long-lasting release and enhancement of Met-Enk production. The role of Met-Enk needs farther investigation. Less
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