Induction of Anesthesia with Halothane Increases Plasma Norepinephrine Concentrations

Joyce, Jeffrey T.; Roizen, Michael F.; Gerson, John I.; Grobecker, H.; Eger, Edmond I.; Forbes, A. R.

doi:10.1097/00000542-198204000-00010

Cited by 27 publications

(4 citation statements)

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“…Our data clearly support an exclusively excitatory role for GABA that is mediated through the selective expression of NKCC1 but not KCC2. It also suggests that clinically relevant drugs that interact with GABA A receptors including anesthetics and other neuroactive agents like benzodiazepines and barbiturates may have stimulatory effects on catecholamine release (Joyce et al 1982;Kitayama et al 1989). Further studies will be needed to determine if this is the case and to elucidate other functional consequences of the elevated [Cl Ϫ ] found in chromaffin cells.…”

Section: Discussionmentioning

confidence: 99%

Role of Cl^–Co-Transporters in the Excitation Produced by GABA_AReceptors in Juvenile Bovine Adrenal Chromaffin Cells

Xie

Currie

Cahill

et al. 2003

Journal of Neurophysiology

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GABA is the primary inhibitory neurotransmitter in the adult mammalian brain. However, in neonatal animals, activation of Cl(-)-permeable GABA receptors is excitatory and appears to depend on the expression of a Na(+)-K(+)-2Cl- cotransporter (NKCC) that elevates intracellular Cl- levels, leading to a depolarized Cl- equilibrium potential (ECl). The change from excitation to inhibition appears to involve the expression of the K+/Cl- co-transporter, KCC2, which lowers intracellular Cl- levels resulting in a hyperpolarized ECl. In this study, we show that bovine chromaffin cells from 4- to 5-mo-old animals are excited by GABA. Activation of GABAA receptors depolarizes the cells, opens voltage-dependent Ca2+ channels, elevates [Ca2+]i, and promotes the release of catecholamines. Blockade of voltage-dependent Ca2+ channels prevents the elevation of [Ca2+]i by GABA. The extrapolated anion reversal potential in these cells is approximately -28 mV, indicating a resting intracellular anion concentration of approximately 50 mM. Expression of KCC2 protein was not detected in the juvenile chromaffin cells. In contrast, clear expression of NKCC1 was observed. Blockade of NKCC1 should reduce the intracellular Cl- concentration and hyperpolarize ECl. Bumetanide, an NKCC1 blocker, reduced the elevation of [Ca2+]i by GABA. In some cells, activation of GABAA receptors inhibits responses to excitatory neurotransmitters, even though GABA itself is depolarizing. Co-activation of cholinergic and GABAA receptors in chromaffin cells produced elevations in [Ca2+]i that were comparable to those produced by cholinergic receptors alone. Our data showing the selective expression of chloride co-transporters and the resulting strongly depolarized anion reversal potential may help explain how activation of GABAA receptors causes sufficient excitation to elicit catecholamine release from chromaffin cells.

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Section: Discussionmentioning

confidence: 99%

Role of Cl^–Co-Transporters in the Excitation Produced by GABA_AReceptors in Juvenile Bovine Adrenal Chromaffin Cells

Xie

Currie

Cahill

et al. 2003

Journal of Neurophysiology

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“…In the group given thiopentone by infusion, there was a small decrease in plasma noradrenaline concentrations, but there was no change in the other groups, suggesting that thiopentone decreases tonic sympathetic activity Qoyce, Roizen and Eger, 1983).…”

Section: Induction Of Anaesthesia Intravenous Anaesthesiamentioning

confidence: 98%

Sympathoadrenal Responses to Anaesthesia and Surgery

Derbyshire

Smith

1984

British Journal of Anaesthesia

149

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“…In vivo administration of halothane and ethanol is also known to increase circulating catecholamines. For example, patients given halothane/02 by face mask experience significant increases in blood plasma norepinephrine 15 min after induction of unconsciousness, which returns to normal 30-45 min later (Joyce et al, 1982). Because most of the catecholamine content of the body is in the adrenal medulla, the increased plasma content of catecholamines may result from an anesthetic effect on chromaffin granule membranes.…”

Section: Discussionmentioning

confidence: 99%

Steady-state catecholamine distribution in chromaffin granule preparations: a test of the pump-leak hypothesis of general anesthesia

Akeson¹,

Deamer²

1989

Biochemistry

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The molecular mechanism of general anesthesia is not understood. Possible modes of action include binding at a protein site, such as a receptor or channel, or physical effects on membrane lipid properties. The pump-leak hypothesis suggests that anesthetics perturb the bilayer of synaptic vesicles, thereby increasing ionic permeability. This results in decay of proton gradients required for transport and accumulation of neurotransmitters. The subsequent loss of neurotransmitters from synaptic vesicles reduces the efficiency of synaptic transmission and results in the anesthetized state. We have determined the effects of general anesthetics on certain parameters of enzyme activity and membrane permeability relevant to the pump-leak hypothesis. We used chromaffin granules as a convenient model system and focused on clinically relevant anesthetic concentrations (ED50), quantitative measurements of permeability changes, and the kinetics of gradient decay. General anesthetics at ED50 have little or no effect on the proton-transport ATPase activity, but do cause modest increments in proton permeability that change the catecholamine distribution in actively pumping chromaffin granule preparations. We found that pH gradients do not collapse entirely under these conditions and that only a fraction of total catecholamine is lost from the chromaffin granules. When total collapse is induced by other means, efflux of catecholamines occurs with a half-time near 30 min. These results suggest that if the pump-leak hypothesis is valid, then very small losses of catecholamines must be sufficient to induce anesthesia. We conclude that the weight of evidence favors other mechanisms, notably direct binding of anesthetics to sensitive proteins.

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Induction of Anesthesia with Halothane Increases Plasma Norepinephrine Concentrations

Cited by 27 publications

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Role of Cl^–Co-Transporters in the Excitation Produced by GABA_AReceptors in Juvenile Bovine Adrenal Chromaffin Cells

Role of Cl^–Co-Transporters in the Excitation Produced by GABA_AReceptors in Juvenile Bovine Adrenal Chromaffin Cells

Sympathoadrenal Responses to Anaesthesia and Surgery

Steady-state catecholamine distribution in chromaffin granule preparations: a test of the pump-leak hypothesis of general anesthesia

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Induction of Anesthesia with Halothane Increases Plasma Norepinephrine Concentrations

Cited by 27 publications

References 0 publications

Role of Cl–Co-Transporters in the Excitation Produced by GABAAReceptors in Juvenile Bovine Adrenal Chromaffin Cells

Role of Cl–Co-Transporters in the Excitation Produced by GABAAReceptors in Juvenile Bovine Adrenal Chromaffin Cells

Sympathoadrenal Responses to Anaesthesia and Surgery

Steady-state catecholamine distribution in chromaffin granule preparations: a test of the pump-leak hypothesis of general anesthesia

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Role of Cl^–Co-Transporters in the Excitation Produced by GABA_AReceptors in Juvenile Bovine Adrenal Chromaffin Cells

Role of Cl^–Co-Transporters in the Excitation Produced by GABA_AReceptors in Juvenile Bovine Adrenal Chromaffin Cells