Inhibition by halothane of potassium‐stimulated acetylcholine release from rat cortical slices

Abstract

1 Cholinergic neurones in the basal forebrain are linked to cortical activation and arousal. 2 The present study was designed to examine the hypothesis that clinically relevant doses of halothane (0.1 to 5%) would significantly reduce depolarization-evoked acetylcholine (ACh) release from rat cortical slices. 3 ACh release was measured from rat cortical slices by a chemiluminescent technique. 4 Depolarization-evoked ACh release was inhibited significantly by halothane with an IC50 of 0.38%. This value equates to 0.3 MAC (the minimum alveolar concentration at which no movement occurs to a standard surgical stimulus in 50% of subjects) for the rat. 5 The potent effect of halothane on ACh release suggests that this mechanism may be a target for the action of volatile anaesthetic agents. This in vitro effect on ACh release is consistent with effects of halothane reported in vivo.

Halothane enhances exocytosis of [3H]‐acetylcholine without increasing calcium influx in rat brain cortical slices

“…Although this apparent discrepancy could be explained by the halothane dose used, tissue and methodological differences should also be taken into account. Moreover, it is worth noting that, as in the present study, Griffiths et al . (1995) reported a trend to an increase in the release of ACh in brain cortical slices from unstimulated samples at all concentrations of halothane tested (0.037–1.19 m M ).…”

“…There are few studies of the effect of volatile general anaesthetics on the release of ACh. In some of these studies, halothane was shown to decrease potassium‐evoked ACh release from rat cortical synaptosomes ( Johnson & Hartzell, 1985 ) and rat cortical slices ( Griffiths et al ., 1995 ). In contrast, no effect on potassium‐stimulated ACh release was observed in rat cerebral cortex in the presence of 1.25% halothane, 3% enflurane or 0.2% methoxyflurane ( Bazil & Minneman, 1989a , 1989b ).…”

“…Although there has been some reports of the action of volatile anaesthetics on ACh release, it is not clear how these drugs alter the release of this transmitter. Some authors reported significant inhibition of potassium‐stimulated release of ACh in the presence of halothane ( Johnson & Hartzell, 1985 ; Griffiths et al ., 1995 ) while others observed no effect ( Bazil & Minneman, 1989a , 1989b ). However, to our knowledge all studies examined the release of ACh from the central nervous system (CNS) using high potassium stimulation, and little effort has been made to follow the effects of anaesthetics on ACh release induced by electrical stimulation.…”

Acetylcholine Release Induced by the Volatile Anesthetic Sevoflurane in Rat Brain Cortical Slices

“…The same result was observed with halothane on pontine ACh release (Keifer et al, 1994). In addition, it was shown that halothane decreases the potassium-evoked ACh release from rat cortical synaptosomes (Johnson and Hartzell, 1985) and rat cortical slices (Griffiths et al, 1995).…”

“…Although there have been some reports of the action of volatile anesthetics on ACh release, it is not clear as to how these drugs alter the release of this transmitter. It was shown that volatile anesthetics decreased the release of ACh in in vitro (Griffiths et al, 1995;Johnson and Hartzell, 1985) and in in vivo systems (Keifer et al, 1994;Shichino et al, 1997;Shichino et al, 1998). However, other studies reported an increase in the release of ACh by halothane (Gomez et al, 1999) and isoflurane from rat brain cortical slices (Gomez et al, 2000), and by halothane in rat striatal slices (Adachi et al, 2001).…”