Effects of thiopental, halothane and isoflurane on the calcium-dependent and -independent release of GABA from striatal synaptosomes in the rat.
The effects of the anesthetic agents thiopental, halothane and isoflurane on the release of GABA induced by depolarization and/or reversal of the GABA carrier were investigated in a synaptosomal preparation obtained from the rat striatum. Veratridine (1 microM) and KCl (9 mM) elicited a significant, Ca(2+)-dependent release of [3H]GABA. The KCl-evoked release was not significantly modified in the presence of nipecotic acid (10(-5) M), a selective blocker of the neuronal GABA carrier. The [3H]GABA release was significantly decreased by omega-conotoxin (10(-7) M, a blocker of the N voltage-dependent Ca2+ channels, but was affected by neither nifedipine (10(-4) M) nor omega-Aga-IVA (10(-7) M which block the L and P Ca2+ channels, respectively. Thiopental application (10(-5) to 10(-3) M) was followed by a dose-related, significant, decrease in both the veratridine and KCl-induced releases, whether nipecotic acid was present or not. In contrast, halothane and isoflurane (1-3%) failed to alter [3H]GABA release. Altogether, these results suggest that reduction of the depolarization-evoked GABA release might contribute to thiopental anesthesia, but this seems unlikely for volatile anesthetics.
Lecharny
J B
JB
Institut National de la Santé et de la Recherche Médicale (INSERM U408), Faculté de Médecine Xavier Bichat, Paris, France.
Salord
F
F
Henzel
D
D
Desmonts
J M
JM
Mantz
J
J
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006221:Halothane / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009557:Nipecotic Acids / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D013874:Thiopental / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000777:Anesthetics; D009557:Nipecotic Acids; C030278:nipecotic acid; D005680:gamma-Aminobutyric Acid; D014701:Veratridine; D011392:Proline; C010983:homoproline; D007530:Isoflurane; D013874:Thiopental; D002118:Calcium; D006221:Halothane