The Function of Opioid Peptides Derived from Adrenal Medulla - Relationship to Stress and Immune System -

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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 … More 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