Effects of clinically effective concentrations of halothane on adrenergic and cholinergic synapses in rat brain in vitro.
The effects of clinically relevant concentrations of halothane on various synaptic events in rat brain were examined in vitro. Slices or membranes prepared from various brain regions were equilibrated with 1.25% halothane at 37 degrees C, resulting in tissue concentrations greater than those found in brains of completely anesthetized animals (greater than 40 nmol/mg of lipid). Under these conditions, no effects of halothane were observed on agonist or antagonist binding to alpha-1 adrenergic, beta adrenergic, alpha-2 adrenergic or muscarinic cholinergic receptors, or on the ability of 5'-guanylylimidodiphosphate to reduce agonist binding affinity. This concentration of halothane also had no effect on norepinephrine-stimulated cyclic AMP accumulation, or inositol phosphate accumulation in response to norepinephrine, carbachol, histamine or 5-hydroxytryptamine. Halothane did reduce potassium-evoked release of [3H]norepinephrine from slices of rat cerebral cortex although it did not affect potassium-evoked release of [3H]acetylcholine. These results suggest that halothane may be relatively specific in its synaptic actions and may affect depolarization-evoked release of norepinephrine at concentrations achieved clinically.
Bazil
C W
CW
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia.
Minneman
K P
KP
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D006221:Halothane / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011950:Receptors, Cholinergic / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects*
D007295:Inositol Phosphates; D011941:Receptors, Adrenergic; D011950:Receptors, Cholinergic; D000242:Cyclic AMP; D000109:Acetylcholine; D006221:Halothane; D009638:Norepinephrine