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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In SH-SY5Y cells, activation of δ-opioid receptors with [d-Pen2,5]-enkephalin (DPDPE; 1 µm) did not alter the intracellular free Ca2+ concentration [Ca2+]i. However, when DPDPE was applied during concomitant Gq-coupled m3 muscarinic receptor stimulation by carbachol or oxotremorine-M, it produced an elevation of [Ca2+]i. The DPDPE-evoked increase in [Ca2+]i was abolished when the carbachol-sensitive intracellular Ca2+ store was emptied. There was a marked difference between the concentration–response relationship for the elevation of [Ca2+]i by carbachol (EC50 13 µm, Hill slope 1) and the concentration–response relationship for carbachol's permissive action in revealing the δ-opioid receptor-mediated elevation of [Ca2+] (EC50 0.7 mm; Hill slope 1.8). Sequestration of free G protein βγ dimers by transient transfection of cells with a βγ binding protein (residues 495–689 of the C terminal tail of G protein-coupled receptor kinase 2) reduced the ability of δ opioid receptor activation to elevate [Ca2+]i. However, DPDPE did not elevate either basal or oxotremorine-M-evoked inositol phosphate production indicating that δ-opioid receptor activation did not stimulate phospholipase C. Furthermore, δ-opioid receptor activation did not result in the reversal of muscarinic receptor desensitization, membrane hyperpolarization or stimulation of sphingosine kinase. There was no coincident signalling between the δ-opioid receptor and the lysophosphatidic acid receptor which couples to elevation of [Ca2+]i in SH-SY5Y cells by a PLC-independent mechanism. In SH-SY5Y cells the coincident signalling between the endogenously expressed δ-opioid and m3 muscarinic receptors appears to occur in the receptor activation-Ca2+ release signalling pathway at a step after the activation of phospholipase C.
    Type of Medium: Electronic Resource
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