μ-Opioid agonists inhibit the enhanced intracellular Ca2+ responses in inflammatory activated astrocytes co-cultured with brain endothelial cells
Artikel i vetenskaplig tidskrift, 2008

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.

inflammatory activators

pain-transmitting peptides

astrocyte

opioids

calcium

endothelial cells

Författare

Elisabeth Hansson

Göteborgs universitet

Anna Westerlund

Göteborgs universitet

Ulrika Björklund

Göteborgs universitet

Torsten Olsson

Chalmers, Signaler och system, Signalbehandling och medicinsk teknik, Medicinska signaler och system

Neuroscience

0306-4522 (ISSN)

Vol. 155 4 1237-1249

Ämneskategorier

Medicinsk laboratorie- och mätteknik

Neurovetenskaper

DOI

10.1016/j.neuroscience.2008.04.027