title: Halothane induces vesicular and carrier-mediated release of [3H]serotonin from rat brain cortical slices.
abstract: The serotonergic system may play a role during general anesthesia but the effect of the volatile anesthetic halothane on the release of serotonin (5-HT) is not fully understood. Rat brain cortical slices were labeled with [3H]5-HT to investigate the effects of halothane on the release of this neurotransmitter from the central nervous system. Halothane induced an increase on the release of [3H]5-HT that was dependent on incubation time and anesthetic concentration (0.006, 0.012, 0.024, 0.036, 0.048 and 0.072 mM). This effect was independent of extracellular calcium and was not affected by tetrodotoxin (blocker of voltage dependent Na+ channels). In contrast, the halothane-evoked [3H]5-HT release was reduced by BAPTA-AM, a membrane-permeable BAPTA analog that chelates intracellular Ca2+. The anesthetic-induced [3H]5-HT release depends on the ryanodine-sensitive intracellular calcium store since it was blocked by dantrolene and azumolene (inhibitors of the calcium-release through ryanodine receptors) but was not affected by aminoethoxydiphenylborate (2-APB), an inhibitor of inositol 1,4,5-triphosphate receptor. The [3H]5-HT release induced by halothane comes mainly from the vesicular pool since it was reduced in about 70% by reserpine, a blocker of vesicular monoamine transporter. The halothane-evoked release of [3H]5-HT release is reduced by fluoxetine, an inhibitor of 5-HT uptake, and the volatile agent also decreased the uptake of [3H]5-HT into rat brain cortical slices. Moreover, a decrease on halothane-induced release of [3H]5-HT was also observed when the brain cortical slices were incubated at low temperature, which is known to interfere with the carrier-mediated release of the neurotransmitter. Ouabain, a Na+/K+ ATPase pump inhibitor, which induces 5-HT release through reverse transport, also decreased [3H]5-HT release induced by halothane, confirming the involvement of a carrier-mediated release of the neurotransmitter in the presence of halothane. In conclusion, these data suggest that halothane induces vesicular and carrier-mediated release of [3H]5-HT in rat brain cortical slices.
authors.affiliation: Department of Pharmacology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Juliara Henriques
authors.initials: JH
authors.lastname: Silva
authors.forename: Marcus Vinicius
authors.initials: MV
authors.lastname: Gomez
authors.forename: Janice Henriques
authors.initials: JH
authors.lastname: Silva
authors.forename: Cristina
authors.initials: C
authors.lastname: Guatimosim
authors.forename: Renato Santiago
authors.initials: RS
authors.lastname: Gomez
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006221:Halothane / Q000494:pharmacology*; D008297:Male; D009924:Organ Culture Techniques; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013572:Synaptic Vesicles / Q000187:drug effects* / Q000378:metabolism; D014316:Tritium; D050493:Vesicular Monoamine Transport Proteins / Q000187:drug effects / Q000378:metabolism
chemical_list: D018685:Anesthetics, Inhalation; D002352:Carrier Proteins; D006221:Halothane; D019837:Ryanodine Receptor Calcium Release Channel; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D000254:Sodium-Potassium-Exchanging ATPase; D014316:Tritium; D050493:Vesicular Monoamine Transport Proteins