Kappa-opioid receptors on astrocytes stimulate L-type Ca2+ channels.
Cultured astrocytes from the cerebral cortex of the rat respond to opioid kappa-receptor stimulation with a substantial elevation of the cytoplasmic free calcium, visualized through the use of the fluorescent calcium indicator Fura-2. The stimulation of kappa-receptors with U-50488H increases the level of calcium through a dose-related stimulatory effect on the transmembrane calcium influx. The kappa-receptor stimulation was completely blocked by the selective kappa-receptor blocker nor-binaltorphimine. Furthermore, the transmembrane calcium influx was completely blocked by nifedipine, indicating the involvement of L-type channels. The presence of L-type channels was verified by stimulation of L-type channels with Bay K8644. The effects of Bay K8644 were completely blocked by nifedipine. L-type channel-coupled kappa-receptors on astrocytes might represent a novel mechanism contributing to the depressant action of opioids on synaptic transmission via decreasing the availability of extracellular calcium necessary for presynaptic transmitter release.
Institute of Neurobiology, University of Göteborg, Sweden.
P S
PS
Eriksson
M
M
Nilsson
M
M
Wågberg
E
E
Hansson
L
L
Rönnbäck
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007150:Immunohistochemistry; D007700:Kinetics; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D000700:Analgesics; D015220:Calcium Channels; D005904:Glial Fibrillary Acidic Protein; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D002118:Calcium