Partial colocalization of glucocorticoid and mineralocorticoid receptors in discrete compartments in nuclei of rat hippocampus neurons.

The glucocorticoid receptor and the mineralocorticoid receptor are hormone-dependent transcription factors. They regulate the excitability of rat hippocampus CA1 neurons in a coordinated fashion. We studied the spatial distribution of these transcription factors in nuclei of CA1 neurons by dual labeling immunocytochemistry and confocal microscopy, combined with novel image restoration and image analysis techniques. We found that both receptors are concentrated in about one thousand clusters within the nucleus. Some clusters contain either mineralocorticoid receptors or glucocorticoid receptors, but a significant number of clusters contains both receptors. These results indicate that the two receptor types are targeted to specific compartments in the nucleus. The coordinated action of the glucocorticoid and mineralocorticoid receptor on gene expression may be established in a specific set of nuclear domains that contain both receptors.

Brain mineralocorticoid receptor diversity: functional implications.

Mineralocorticoid receptors (MRs) in neurons of the anterior hypothalamus and the periventricular brain regions mediate aldosterone-selective actions on sodium homeostasis, salt appetite and cardiovascular regulation. Corticosterone is not effective in these neurons, possibly because it is enzymatically inactivated. However, MRs in limbic brain regions, notably in the hippocampal neurons, do already respond to very low concentrations of both corticosterone and aldosterone. The MR-mediated effects stabilize neuronal transmission and appear critical for neuronal integrity of a sub-region of the hippocampus: the dentate gyrus. Higher concentrations of corticosterone induced by stress and the circadian rise progressively activate the lower affinity glucocorticoid receptors (GRs), which in coordination with MR-mediated actions then facilitate adaptive processes required for recovery of homeostasis. It is postulated that this balanced MR- and GR-mediated action of corticosterone is of critical importance for regulation of the stress response and behavioural adaptation.

Pharmacological comparison of the rat and guinea-pig cortical high affinity 5-hydroxytryptamine uptake system.

The pharmacological characteristics of the high affinity [3H]5-hydroxytryptamine ([3H]5-HT) uptake system were investigated in the cerebral cortex of the rat and guinea-pig. In crude cortical synaptosomal preparations from the rat and guinea-pig, [3H]5-HT accumulated with high affinity (Km, 72 +/- 12 and 57 +/- 14 nM for rat and guinea-pig cortical synaptosomal preparation, respectively, mean +/- SEM, N = 5) and with a comparable maximum activity (Vmax, 1.22 +/- 0.21 and 0.90 +/- 0.19 pmol/min/mg protein for rat and guinea-pig cortical synaptosomal preparation, respectively, mean +/- SEM, N = 5). Competition studies employing a range of structurally diverse competing compounds showed that the [3H]5-HT uptake was pharmacologically similar in both preparations. However, citalopram possessed approximately 10-fold weaker affinity to prevent [3H]5-HT uptake in the guinea-pig preparation when compared to the rat and all of the tricyclic antidepressants assessed in the present studies (amitriptyline, nortriptyline, desipramine and imipramine) displayed higher affinity in the guinea-pig preparation when compared to the rat. It is concluded that the high affinity 5-HT uptake systems in the rat and guinea-pig cortex are similar but may not be identical.

Pharmacological comparison of the sigma recognition site labelled by [3H]haloperidol in human and rat cerebellum.

The radioligand binding characteristics of [3H]haloperidol (in the presence of spiperone, 25 nmolL-1) were investigated in rat and human cerebellar membranes. In both rat and human cerebellar membrane preparations saturation studies with [3H]haloperidol (non-specific binding defined by pentazocine, 10 mumolsL-1) demonstrated high affinity saturable specific binding to a homogenous population of binding sites (rat, Bmax 6693 +/- 1242 fmol mg-1 protein, pKD 8.33 +/- 0.08; human, Bmax 2550 +/- 437 fmol mg-1 protein, pKD 8.59 +/- 0.11; mean +/- SEM, n = 3-6). Competition studies employing a wide range of structurally diverse competing compounds displayed that the [3H]haloperidol binding site was pharmacologically similar in both preparations and comparable to sigma recognition sites previously identified in various tissues originating from different species. In addition, with reference to the potential subtypes of sigma recognition sites, the labelling of these sites by low nanomolar concentrations of [3H]haloperidol provides evidence that they belong to the sigma-1 recognition site subtype. The present findings suggest that the pharmacology of the rat and human cerebellar sigma recognition site are directly comparable and provides further supporting evidence towards the use of [3H]haloperidol radioligand binding studies in the rat to detect sigma receptor ligands with potential therapeutic activity.

Early detection of open fires and spontaneous combustion in mines.

Until fairly recently the detection of heatings was based on men seeing or smelling smoke and the laboratory analysis of mine air samples. Continuous monitoring of carbon monoxide by means of tube bundle systems has been a big step forward in detecting spontaneous combustion of coal and has found widespread acceptance in U.K. mines; general fire detection relies on shaft monitors. Both are based on infra-red analysers like the Unor CO-analysers that can be installed underground. In recent years British laboratories have developed and adapted several devices based on other principles: ionisation, semi-conductors, electro-chemical cells, thermistors, detection "thermal noise", infra-red imagers. All these instruments are briefly described by the authors in this paper presented by Mr. Makower.