Receptor-coupled uptake of valproate in rat astroglial primary cultures.
Various receptor ligands were investigated for their effects on the uptake of the antiepileptic drug valproic acid (VPA) in primary astroglial cultures from cerebral cortex of neonatal rats. After stimulation with the alpha 1-adrenoceptor agonist phenylephrine, 5-hydroxytryptamine (5-HT) or the glutamate receptor agonists glutamate, quisqualate and kainate, the Vmax and Km values for the drug transport increased. On the contrary, after exposure to the alpha 2-adrenoceptor agonist clonidine, Vmax and Km decreased. The effects were reversed in comparison to the control level in the presence of selective receptor antagonists. The data indicate a specific coupling between receptors and the uptake system for VPA. Furthermore, the results may have significant implications, as they suggest that receptors on astrocytes can be involved in the local regulation of drug transport in brain.
Institute of Neurobiology, University of Göteborg, Sweden.
M
M
Nilsson
L
L
Rönnbäck
E
E
Hansson
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003000:Clonidine / Q000494:pharmacology; D004347:Drug Interactions; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D007545:Isoproterenol / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D014635:Valproic Acid / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
D005971:Glutamates; D011810:Quinoxalines; D017981:Receptors, Neurotransmitter; D010656:Phenylephrine; D015016:Yohimbine; D012701:Serotonin; D018698:Glutamic Acid; D014635:Valproic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D016318:Quisqualic Acid; D007650:Ketanserin; D007545:Isoproterenol; D003000:Clonidine; D007608:Kainic Acid; D011224:Prazosin