Possible involvement of ATP-sensitive K+ channels in the inhibition of rat central adrenergic neurotransmission under hypoxia.
By using rat brain cortical slices preloaded with [3H]norepinephrine, we examined whether ATP-sensitive K+ channels are involved in altered adrenergic neurotransmission during hypoxia. The tritium overflow evoked by transmural nerve stimulation (TNS) was significantly inhibited at 5 min of hypoxia and reached the maximum inhibition at 20 min. The inhibition of the TNS-evoked tritium overflow under a 20-min hypoxia was reversed by subsequent reoxygenation and was concentration-dependently antagonized by glibenclamide (0.1 and 1 microM). 86Rb+ efflux was increased after introduction of hypoxia and reached the peak value at about 20 min, which was concentration-dependently antagonized by glibenclamide (0.1-10 microM). Hypoxia decreased cortical ATP content. Linear correlations were mutually observed among the changes by hypoxia in the TNS-evoked tritium overflow, tissue ATP content and 86Rb+ efflux. The spontaneous tritium outflow was inhibited only after hypoxic periods of more than 16 min, the inhibition being reversed by reoxygenation and antagonized by 1 microM glibenclamide. These results suggest that the inhibition of rat central adrenergic neurotransmission during hypoxia may be associated with an activation of ATP-sensitive K+ channels.
Takata
Y
Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Shimada
F
F
Kato
H
H
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009044:Motor Cortex / Q000378:metabolism / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012413:Rubidium / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D014316:Tritium / Q000378:metabolism
D015221:Potassium Channels; D014316:Tritium; D000255:Adenosine Triphosphate; D003042:Cocaine; D012413:Rubidium; D005905:Glyburide; D009638:Norepinephrine