Abstract— Desheathed rat dorsal root ganglia were incubated in a medium containing amino‐oxyacetic acid and [3H]GABA. Under these conditions, [3H]GABA is taken up exclusively by the satellite glial cells in the ganglia. Efflux of [3H]GABA from the tissue was measured after passing the ganglia through a series of wash solutions. The spontaneous efflux of radioactivity, mostly [3H]GABA, was more rapid in the absence of amino‐oxyacetic acid in the incubation and wash media. Raising the potassium concentration in the wash media caused an increase in the efflux of [3H]GABA. This increase was sigmoidally related to the potassium concentration in the wash media, reaching a maximum at 64 mm‐K+. The releasing effect of K+ was inhibited by removing calcium from the media. Reducing the calcium and raising the magnesium concentration in the wash solutions inhibited the increased efflux of [3H]GABA due to 64 mm‐K+ by 48 per cent, while 5 mM‐La3+ and diphenylhydantoin (0·005 and 0·5 mm) had no effect on this increase. Only a small increase in the efflux of [14C]glutamate was produced by 64 mm‐K+ and it had no effect upon the effluxes of [3H]glycine, [3H]alanine or [3H]leucine. The efflux of lactate dehydrogenase was similarly unaffected by 64 mM‐K+. The results suggest that glial cells in spinal ganglia can respond to depolarizing concentrations of potassium by releasing GABA in a calcium‐dependent process.

The effect of various concentrations of thiopentone, pentobarbitone, methohexitone, hydroxydione, alphaxalone/alphadolone, ketamine, α‐chloralose and urethane on the transport of radiolabelled γ‐aminobutyric acid (GABA) and D‐aspartate was investigated. Uptake of the amino acids was weakly inhibited, if at all, by the anaesthetics and it is unlikely that such effects contribute significantly to their physiological function. The spontaneous efflux of GABA and D‐aspartate was not detectably altered by any of the drugs tested. Thiopentone, pentobarbitone, methohexitone and hydroxydione inhibited K+‐stimulated GABA and D‐aspartate release. The other anaesthetics had no effect on K+‐stimulated amino acid release. The rank order of potency of the inhibitors of K+‐stimulated amino acid release did not correlate with their anaesthetic potency. Furthermore not all inhibitors appeared to be very effective at anaesthetic concentrations. It is concluded that although it is possible that inhibition of excitatory transmitter release may be involved in the anaesthetic action of some anaesthetics, for many of the substances tested in this study such a mechanism does not appear to be implicated.

No abstract

The specific binding of [3H]WAY‐100635 {N‐[2‐[4‐(2‐[O‐methyl‐3H]methoxyphenyl)‐1‐piperazinyl]ethyl]‐N‐(2‐pyridinyl)cyclohexane carboxamide trihydrochloride} to rat hippocampal membrane preparations was time, temperature, and tissue concentration dependent. The rates of [3H]WAY‐100635 association (k+1 = 0.069 ± 0.015 nM−1 min−1) and dissociation (k−1 = 0.023 ± 0.001 min−1) followed monoexponential kinetics. Saturation binding isotherms of [3H]WAY‐100635 exhibited a single class of recognition site with an affinity of 0.37 ± 0.051 nM and a maximal binding capacity (Bmax) of 312 ± 12 fmol/mg of protein. The maximal number of binding sites labelled by [3H]WAY‐100635 was ∼36% higher compared with that of 8‐hydroxy‐2‐(di‐n‐[3H]‐propylamino)tetralin ([3H]8‐OH‐DPAT). The binding affinity of [3H]WAY‐100635 was significantly lowered by the divalent cations CaCl2 (2.5‐fold; p < 0.02) and MnCl2 (3.6‐fold; p < 0.05), with no effect on Bmax. Guanyl nucleotides failed to influence the KD and Bmax parameters of [3H]WAY‐100635 binding to 5‐HT1A receptors. The pharmacological binding profile of [3H]WAY‐100635 was closely correlated with that of [3H]8‐OH‐DPAT, which is consistent with the labelling of 5‐hydroxytryptamine1A (5‐HT1A) sites in rat hippocampus. [3H]WAY‐100635 competition curves with 5‐HT1A agonists and partial agonists were best resolved into high‐ and low‐affinity binding components, whereas antagonists were best described by a one‐site binding model. In the presence of 50 µM guanosine 5′‐O‐(3‐thiotriphosphate) (GTPγS), competition curves for the antagonists remained unaltered, whereas the agonist and partial agonist curves were shifted to the right, reflecting an influence of G protein coupling on agonist versus antagonist binding to the 5‐HT1A receptor. However, a residual (16 ± 2%) high‐affinity agonist binding component was still apparent in the presence of GTPγS, indicating the existence of GTP‐insensitive sites.