Neurochem Int. 1984;6(2):237-44. doi: 10.1016/0197-0186(84)90098-6.

Alterations in cerebral ?-adrenergic receptor-adenylate cyclase system induced by halothane, ketamine and ethanol.

Neurochemistry international

C Okuda, M Miyazaki, K Kuriyama

PMID: 20488043 DOI: 10.1016/0197-0186(84)90098-6

Abstract

The effect of halothane, ketamine and ethanol on ?-adrenergic receptor adenylate cyclase system was studied in the brain of rats. An anesthetic concentration of halothane and ketamine added in vitro decreased the stimulatory effect of norepinephrine on cyclic AMP formation in slices from the cerebral cortex. On the other hand, ethanol increased the basal activity of cerebral adenylate cyclase without affecting on the norepinephrine-stimulated activity. The increase of the basal activity induced by ethanol was not antagonized by propranolol, a ?-adrenergic antagonist. In the crude synaptosomal (P(2)) fraction, these drugs had no significant effect on the basal adenylate cyclase activity, binding of [(3)H]dihydroalprenolol to ?-receptor, and binding of [(3)H]guanylylimido diphosphate ([(3)H]Gpp(NH)p) to guanyl nucleotide binding site. In contrast, the adenylate cyclase activity stimulated by Gpp(NH)p or NaF was significantly inhibited by an anesthetic concentration of these drugs. An anesthetic concentration of these drugs increased the membrane fluidity of P(2) fraction monitored by the fluorescence polarization technique. The addition of linoleic acid (more than 500 ?M) also induced not only the increase of fluidity, but also the decrease of Gpp(NH)p- or NaF-stimulated adenylate cyclase activity in the cerebral P(2) fraction. The present results suggest that general anesthetics may interfere with the guanyl nucleotide binding regulatory protein-mediated activation of cerebral adenylate cyclase by disturbing the lipid region of synaptic membrane.

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