Table 3.
Effect of halothane, pentobarbital, and ethanol on the evoked catecholamine release from peripheral organs and brain tissue
| Ligand-gated cation channels | Activation of Gq protein-coupled receptors | Voltage-dependent cation channels | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| NMDA | Kainate | nACh | 5-HT3 | Histamine H1 | mACh | K+ | Veratridine | Electrical stimulation | |||
| IC50 | |||||||||||
| Halothane | 1Bovine adrenal medulla | 0.25 | 4.6 | > 4.3 | > 4.3 | > 14 | mM | ||||
| Halothane | 2Rabbit heart | 0.06 | > 1 | > 1 | mM | ||||||
| Pentobarbital | 3Rabbit heart | 34 | 190 | 440 | μM | ||||||
| Ethanol | 4Rabbit heart | 129 | 203 | 830 | 1150 | mM | |||||
| Ethanol | 5Human cortex | 90 | 115 | > 150 | > 150 | mM | |||||
| Ethanol | 6Rat cortex | 45 | 126 | > 320 | > 320 | mM | |||||
To evoke catecholamine release from bovine adrenal medulla chromaffine cells and noradrenaline release from noradrenergic nerve terminals, intracellular Ca2+ was increased by activation of ligand-gated or voltage-dependent cation channels or of Gq protein-coupled receptors. The table shows that the inhibitory potency of the three agents (IC50, concentration leading to an inhibition of 50%) at ligand-gated channels is higher than at Gq protein-coupled receptors and voltage-dependent cation channels. Within the ligand-gated ion channels, the potency towards NMDA receptors is higher than that towards nACh and 5-HT3 receptors. Inhibition of the nACh receptor-mediated inhibition of catecholamine/noradrenaline release may contribute to the clinical effect of halothane and pentobarbital. Thus, the IC50 of halothane is close to its MAC in saline of 0.24 mM (the MAC (minimal alveolar concentration) is a parameter of the potency of a general anesthetic). The IC50 of pentobarbital is within the range of the plasma/serum concentration (4.4-44 μM) obtained under treatment with this barbiturate. Inhibition of the NMDA-induced noradrenaline release in human cortex may contribute to the toxic effect of ethanol 2‰ (= 46 mM; inhibition by ~ 40% at this concentration). Derived from 1Göthert (1972) and Göthert et al. (1976a), 2Göthert (1974), 3Göthert and Rieckesmann (1978), 4Göthert and Thielecke (1976) and Göthert et al. (1979a), 5Fink et al. (1992a), and 6Göthert and Fink et al. (1989) and Fink and Göthert (1990)