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mu-Opioid agonists inhibit the enhanced intracellular Ca(2+) responses in inflammatory activated astrocytes co-cultured with brain endothelial cells.
Neuroscience 2008; 155(4):1237-49N

Abstract

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 Ca(2+) amplitudes and/or more Ca(2+) 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 Ca(2+) release in the presence of the inflammatory or pain mediating activators substance P, calcitonin gene-related peptide (CGRP), lipopolysaccharide (LPS), or leptin. These Ca(2+) responses were restored by opioids so that the delta- and kappa-opioid receptor agonists reduced the number of Ca(2+) transients elicited after incubation in substance P+CGRP or leptin, while the mu- and delta-opioid receptor agonists attenuated the Ca(2+) 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 Ca(2+) 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.

Authors+Show Affiliations

Department of Clinical Neuroscience and Rehabilitation, The Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden. elisabeth.hansson@neuro.gu.seNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18692967

Citation

Hansson, E, et al. "Mu-Opioid Agonists Inhibit the Enhanced Intracellular Ca(2+) Responses in Inflammatory Activated Astrocytes Co-cultured With Brain Endothelial Cells." Neuroscience, vol. 155, no. 4, 2008, pp. 1237-49.
Hansson E, Westerlund A, Björklund U, et al. Mu-Opioid agonists inhibit the enhanced intracellular Ca(2+) responses in inflammatory activated astrocytes co-cultured with brain endothelial cells. Neuroscience. 2008;155(4):1237-49.
Hansson, E., Westerlund, A., Björklund, U., & Olsson, T. (2008). Mu-Opioid agonists inhibit the enhanced intracellular Ca(2+) responses in inflammatory activated astrocytes co-cultured with brain endothelial cells. Neuroscience, 155(4), pp. 1237-49. doi:10.1016/j.neuroscience.2008.04.027.
Hansson E, et al. Mu-Opioid Agonists Inhibit the Enhanced Intracellular Ca(2+) Responses in Inflammatory Activated Astrocytes Co-cultured With Brain Endothelial Cells. Neuroscience. 2008 Sep 9;155(4):1237-49. PubMed PMID: 18692967.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - mu-Opioid agonists inhibit the enhanced intracellular Ca(2+) responses in inflammatory activated astrocytes co-cultured with brain endothelial cells. AU - Hansson,E, AU - Westerlund,A, AU - Björklund,U, AU - Olsson,T, Y1 - 2008/04/23/ PY - 2008/02/15/received PY - 2008/04/11/revised PY - 2008/04/11/accepted PY - 2008/8/12/pubmed PY - 2009/2/7/medline PY - 2008/8/12/entrez SP - 1237 EP - 49 JF - Neuroscience JO - Neuroscience VL - 155 IS - 4 N2 - 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 Ca(2+) amplitudes and/or more Ca(2+) 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 Ca(2+) release in the presence of the inflammatory or pain mediating activators substance P, calcitonin gene-related peptide (CGRP), lipopolysaccharide (LPS), or leptin. These Ca(2+) responses were restored by opioids so that the delta- and kappa-opioid receptor agonists reduced the number of Ca(2+) transients elicited after incubation in substance P+CGRP or leptin, while the mu- and delta-opioid receptor agonists attenuated the Ca(2+) 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 Ca(2+) 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. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/18692967/mu_Opioid_agonists_inhibit_the_enhanced_intracellular_Ca_2+__responses_in_inflammatory_activated_astrocytes_co_cultured_with_brain_endothelial_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(08)00592-7 DB - PRIME DP - Unbound Medicine ER -