Barbiturates inhibit K+-evoked noradrenaline and dopamine release from ratstriatal slices - involvement of voltage sensitive Ca2+ channels

The cellular target site(s) for anaesthetic action remain unclear. In rat s triatal slices we have previously demonstrated that K+-evoked noradrenaline (NA) and dopamine (DA) release is mediated predominantly via P/Q-type volt age sensitive Ca2+ channels (VSCC). Using this model of Ca2+ dependent tran smitter release we have evaluated the effects of anaesthetic and non-anaest hetic barbiturates. Rat brain striatal slices were incubated in the absence and presence of barbiturate for 10 min at 37 degrees C. The slices were th en incubated for 6 min with 40 mM KCl. All anaesthetic barbiturates produce d a concentration-dependent inhibition of K+-evoked NA and DA release. Non- anaesthetic barbiturate, barbituric acid was ineffective. The pIC(50) for N A and DA release (thiopental: 4.90 +/- 0.13 and 5.00 +/- 0.10, pentobarbita l: 4.39 +/- 0.07 and 4.43 +/- 0.14, phenobarbital: 3.85 +/- 0.08 and 3.59 /- 0.10, respectively) correlated with lipid solubility (NA: r(2) = 0.999, DA: r(2) = 0.987). We therefore suggest that barbiturates inhibit catechola mine release via an interaction with P/Q VSCC further implicating this chan nel in anaesthetic action. (C) 2000 Elsevier Science ireland Ltd. All right s reserved.