期刊
NEUROSCIENCE
卷 155, 期 4, 页码 1237-1249出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2008.04.027
关键词
astrocyte; calcium; endothelial cells; inflammatory activators; opioids; pain-transmitting peptides
资金
- Swedish Research Council [33X-06812-23]
- Edith Jacobsson's Foundation
- Kungl. Vetenskaps- och Vitterhets-Samhallet i Goteborg (KVVS)
- Folksams Forskningsstiftelse
- Arvid Carlsson's Foundation
- Sahlgrenska University Hospital, Gothenburg
In order to imitate the in vivo situation with constituents from the blood-brain barrier, astrocytes from newborn rat cerebral cortex were co-cultured with adult rat brain microvascular endothelial cells. These astrocytes exhibited a morphologically differentiated appearance with long processes. 5-HT, synthetic mu-, delta- or kappa-opioid agonists, and the endogenous opioids endomorphin-1, beta-endorphin, and dynorphin induced higher Ca2+ amplitudes and/or more Ca2+ transients in these cells than in astrocytes in monoculture, as a sign of more developed signal transduction systems. Furthermore, stimulation of the co-cultured astrocytes with 5-HT generated a pronounced increase in intracellular Ca2+ release in the presence of the inflammatory or pain mediating activators substance P, calcitonin gene-related peptide (CGRP), lipopolysaccharide (LPS), or leptin. These Ca2+ responses were restored by opioids so that the delta- and kappa-opiold receptor agonists reduced the number of Ca2+ transients elicited after incubation in substance P+CGRP or leptin, while the mu- and delta-opioid receptor agonists attenuated the Ca2+ amplitudes elicited in the presence of LPS or leptin. In LPS treated co-cultured astrocytes the mu-opioid receptor antagonist naloxone attenuated not only the endomorphin-1, but also the 5-HT evoked Ca2+ transients. These results suggest that opioids, especially mu-opioid agonists, play a role in the control of neuroinflammatory activity in astrocytes and that naloxone, in addition to its interaction with mu-opioid receptors, also may act through some binding site on astrocytes, other than the classical opioid receptor. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.
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