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μ-Opioid agonists inhibit the enhanced intracellular Ca2+ responses in inflammatory activated astrocytes co-cultured with brain endothelial cells

Elisabeth Hansson ; Anna Westerlund ; Ulrika Björklund ; Torsten Olsson (Institutionen för signaler och system, Medicinska signaler och system)
Neuroscience (0306-4522). Vol. 155 (2008), 4, p. 1237-1249 .
[Artikel, refereegranskad vetenskaplig]

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 μ-, δ- or κ-opioid agonists, and the endogenous opioids endomorphin-1, β-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 δ- and κ-opioid receptor agonists reduced the number of Ca2+ transients elicited after incubation in substance P+CGRP or leptin, while the μ- and δ-opioid receptor agonists attenuated the Ca2+ amplitudes elicited in the presence of LPS or leptin. In LPS treated co-cultured astrocytes the μ-opioid receptor antagonist naloxone attenuated not only the endomorphin-1, but also the 5-HT evoked Ca2+ transients. These results suggest that opioids, especially μ-opioid agonists, play a role in the control of neuroinflammatory activity in astrocytes and that naloxone, in addition to its interaction with μ-opioid receptors, also may act through some binding site on astrocytes, other than the classical opioid receptor.

Nyckelord: astrocyte; calcium; endothelial cells, inflammatory activators, opioids, pain-transmitting peptides



Denna post skapades 2009-01-08. Senast ändrad 2014-12-09.
CPL Pubid: 84367

 

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Institutioner (Chalmers)

Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering (2006-2016)
Institutionen för signaler och system, Medicinska signaler och system

Ämnesområden

Medicinsk teknik
Neurovetenskap

Chalmers infrastruktur