Effect of ethanol upon respiratory-related hypoglossal nerve output of neonatal rat brain stem slices.
The actions of ethanol (EtOH) on the respiratory output of the neonatal rat brain stem slice preparation in vitro are described. Ethanol inhibited respiratory-related hypoglossal nerve activity in a dose-dependent manner. The effect of EtOH was evident within 5 min and was reversible on EtOH washout. The actions of EtOH were qualitatively similar to those of two other alcohols, methanol and octanol. We investigated the dose-response relationship for each alcohol and determined that the order of potency was methanol < EtOH << octanol, with EC(50) values of 291 mM, 39.7 mM, and 49.2 microM respectively. Application of either strychnine (5 microM) or bicuculline (5 microM) alone, partially but not significantly, reversed the inhibition of respiratory-related hypoglossal nerve activity produced by 50 mM EtOH. Preincubation of rhythmic slices with a combination of both strychnine and bicuculline (both 5 microM) partially, but significantly, blocked the inhibitory actions of EtOH, suggesting that other mechanisms also play a role in the action of EtOH. Preincubation of the slices with 25 microM APV reduced the relative degree of inhibition caused by EtOH suggesting that N-methyl-D-aspartate (NMDA)-receptor-mediated events can be affected by EtOH. Furthermore inhibition of protein kinase C by incubation with 100 nM staurosporine also reduced the efficacy of EtOH. These results suggest that the actions of EtOH may be mediated via glycine, GABA(A), and NMDA receptors and that activation of protein kinase C is involved in the EtOH-induced inhibition of respiratory-related hypoglossal nerve activity.
Gibson
I C
IC
Department of Physiologycs, School of Medicine, University of Washington, Seattle, Washington 98195-7290, USA.
Berger
A J
AJ
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D007002:Hypoglossal Nerve / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology; D000432:Methanol / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology; D013331:Strychnine / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology
D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D013779:Tetrodotoxin; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D011493:Protein Kinase C; D019311:Staurosporine; D013331:Strychnine; D001640:Bicuculline; D000432:Methanol