Comparison of [³H]Choline and d‐[³H]Aspartate Efflux from Guinea Pig and Human Neocortex

Abstract

The outflow of [3H]choline ([3H]Ch) evoked by electrical field stimulation and the efflux of D-[3H]Asp induced by 35 mM KCl and 1-10 microM ouabain were studied in human and guinea pig cortical slices, kept under identical experimental conditions. [3H]Ch outflow was significantly lower whereas D-[3H]Asp efflux was significantly higher in humans than in guinea pigs. This suggests a different proportion of the two neuronal systems in these two species. Blockade of muscarinic autoreceptors with atropine increased, whereas stimulation of alpha 2 receptors with norepinephrine (NE) reduced, the evoked [3H]Ch outflow to the same extent in human and guinea pig cortical slices. Conversely, NE did not affect ouabain-induced D-[3H]Asp efflux, suggesting that an alpha 2-mediated control is not operative in the glutamatergic cortical structures. Desmethylimipramine, 2-5 microM, was able to increase [3H]Ch outflow through atropine-like mechanisms only in the human. This drug at 20-50 microM inhibited [3H]Ch and D-[3H]Asp efflux in both species, through mechanisms unrelated to its monoamine reuptake blocking properties. Thus, similarities and differences can be detected between humans and guinea pigs with regard to (a) the relative potency of the cholinergic and acidic amino acidergic signals and (b) the modulation of neurotransmitter outflow by drugs acting on auto- and the heteroreceptors.

Functional Pharmacology in Human Brain

“…In particular, a number of studies were published in the early 1990s dealing with muscarinic autoreceptors mediating inhibition of acetylcholine (ACh) release from human neocortex tissues (Feuerstein et al, 1990(Feuerstein et al, , 1992Marchi et al, 1990;Beani et al, 1992). These works have already been considered in my previous review (Raiteri, 1994).…”

“…However, functional studies of adrenergic receptors in human brain have focused exclusively on ␣ 2 -receptors regulating neurotransmitter release. Of these studies, those describing ␣ 2 -adrenergic regulation of ACh and glutamate release (Beani et al, 1992), of GABA release (Ferraro et al, 1993) and of serotonin release Feuerstein et al, 1993) from human cerebral cortex tissues have already been considered in my previous review (Raiteri, 1994).…”

Neutrotransmitter Release and Uptake

“…1988, 1989;Burke et aI., 1993;Galarreta el ai., 1993;Fleck et al .. 1993;Kimura el at., 1995) or electrical field-stimulated (Szerb, 1988) Ca 2 'dependent release. Ca 2 +-dependent release of CH]-D-aspartate from slice preparations has been reported in cerebellar (Bosley et at.. 1983), hippocampal (Simonato et al, 1993: Gaur et al, 1994: Keith et aI., 1994 and cortical slices (Palmer and Reiter, 1994, but see Beani et al,1992). Ca 2 +-dependent release of CH]-D-aspartate from slice preparations has been reported in cerebellar (Bosley et at.. 1983), hippocampal (Simonato et al, 1993: Gaur et al, 1994: Keith et aI., 1994 and cortical slices (Palmer and Reiter, 1994, but see Beani et al,1992).…”