Nups, Kaps, NXFs and others: making sense in the Babel of nuclear transport.

The spatio-temporal aspects of signal transduction, and the molecular basis of nucleocytoplasmic transport, have attracted much attention recently. How they might be linked was the theme of a recent conference*. Many aspects of nuclear transport were discussed and novel results presented, either in talks or posters, by the approximately 80 participants.

[Pharmacological approach to failures of antidepressant treatment].

Depression, a chronic disease and a leading cause of disability worldwide, will generate increasing needs in terms of public health in the coming years. Many antidepressants are now available. However, these molecules present real limitations and disadvantages.

[Pharmacological management of failure of treatment with antidepressants].

Depression, a chronic disease and a leading cause of disability worldwide, will generate increasing needs in terms of public health in the coming years. Many antidepressants are now available. However, these molecules present real limitations and disadvantages.

cAMP-dependent protein kinase phosphorylates and activates nuclear Ca2+-ATPase.

A Ca2+-pump ATPase, similar to that in the endoplasmic reticulum, has been located on the outer membrane of rat liver nuclei. The effect of cAMP-dependent protein kinase (PKA) on nuclear Ca2+-ATPase (NCA) was studied by using purified rat liver nuclei. Treatment of isolated nuclei with the catalytic unit of PKA resulted in the phosphorylation of a 105-kDa band that was recognized by antibodies specific for sarcoplasmic reticulum Ca2+-ATPase type 2b.

Pervanadate elicits proliferation and mediates activation of mitogen-activated protein (MAP) kinase in the nucleus.

There is growing evidence for the role of protein tyrosine phosphatases in controlling such fundamental cellular processes as growth and differentiation. Pervanadate is a potent inhibitor of protein tyrosine phosphatase which has been observed here to induce proliferation in C3H10T1/2 mouse fibroblasts. Pervanadate also translocated/activated p42/44 mitogen-activated protein (MAP) kinase to the cell nucleus.

Regulation of signalling pathways to the nucleus by dopaminergic receptors.

Dopamine regulates postsynaptic gene expression in the central nervous system. The pattern of gene expression is different from chronic vs acute stimulation of dopaminergic receptors. Signalling to the nucleus through dopamine receptors involves different second messenger systems, and each receptor subtype regulates multiple effectors.

Neuroleptics differentially induce jun family genes in the rat striatum.

The effect of neuroleptics in single administration on the expression of genes of the jun family was studied in the rat striatum. jun B, but not jun D was dose-dependently and transiently induced. This effect was blocked by pretreatment with a specific dopamine D2 agonist.

Impaired gene transcription and nuclear protein kinase C activation in the brain and liver of aged rats.

The expression of the hsp70 and c-fos genes and the activation of nuclear protein kinase C (PKC) were studied in young and aged whole rats under heat-shock conditions. The induction of hsp70 and c-fos genes by heat shock were decreased several fold in the brain as well as in the liver of senescent animals. Nuclear run-off transcription assay indicated that this age-related impairment could be attributed to a block at the level of transcription.

[Regulation of the dopamine D2 receptor gene and the early genes in the CNS by neuroleptics].

The interaction of a ligand with its cognate receptor not only activates signal transduction pathways but also determines adaptive responses affecting key elements in these pathways, in particular the cell surface receptor. Such is the case for G protein-linked receptors, the expression and functional status of which are highly regulated. The regulatory mechanisms involved can be divided according to two distinct time frames, acute and chronic.

Stimulation of nuclear protein kinase C leads to phosphorylation of nuclear inositol 1,4,5-trisphosphate receptor and accelerated calcium release by inositol 1,4,5-trisphosphate from isolated rat liver nuclei.

Rat liver nuclei inositol 1,4,5-trisphosphate receptor (Malviya, A.N., Rogue, P.

Heat stressing stimulates nuclear protein kinase C raising diacylglycerol levels. Nuclear protein kinase C activation precedes Hsp70 mRNA expression.

Protein kinase C (pKC) activity has been studied in rat liver after subjecting animals to heat shocking. Nuclear pKC activity was stimulated owing to heat shocking without any change in the cytosolic enzyme activity. The nuclear diacylglycerol levels were raised owing to heat stress along with the stimulation of polarhead phospholipid hydrolysis.

Dopamine D2 receptor antagonists induce immediate early genes in the rat striatum.

The acute effects of dopamine D2 antagonists and agonists on the expression of c-jun, zif-268, ETR101 and c-fos in the rat striatum were studied. A single injection IP of haloperidol (2 mg/kg) or sulpiride (100 mg/kg) produced a rapid and transient increase in c-jun, zif-268 and c-fos mRNA. ETR101 was not activated.

[Induction by neuroleptics of certain genes in the central nervous system].

Prolonged administration of neuroleptic drugs increases the density of dopamine D2 receptors in several brain regions. We have recently shown that such treatment also raises dopamine D2 receptor mRNA levels in the striatum. To elucidate some of the initial events which lead to this upregulation, we studied the acute effects of dopamine D2 agonists and antagonists on the expression of c-jun and c-fos.

Bio-clinical prevalence or non-prevalence of drug addiction over psychiatric symptomatology.

It has been found that opiate abusers once detoxified are afflicted with personality disorders. An attempt was made to test the origin of drug abuse by comparing a group of drug abusers with personality disorders diagnosed as borderline or schizotypal with a group of people suffering from similar personality disorders but who did not use drugs. The results of the test are discussed.

Up-regulation of dopamine D2 receptor mRNA in rat striatum by chronic neuroleptic treatment.

The effect of prolonged administration of antagonists on rat striatal dopamine D2 receptor binding and mRNA content was examined. Both haloperidol (2 and 4 mg/kg) and sulpiride (10 mg/kg) induced a significant rise in total D2 and D2(444) mRNA level and in Bmax. Regulation of messenger RNA accumulation is thus an important determinant of dopamine D2 receptor density.

[Results of an epidemiological survey conducted with psychiatrists, general practitioners, liberal nurses and social workers in a mental health sector].

An epidemiological survey was carried out, amongst psychiatrists, general practitioners, social workers and liberal nurses, with a double aim. To determine the number of psychiatric cases followed or identified; these were classified according to DSMIII criteria (simplified for use by those interviewers little used to psychiatric jargon), essentially: dementia, depression, schizophrenia, other psychosis, other cases (neurosis, substance abuse, alcoholism). Another aim was to determine how the psychiatric care facilities were perceived and used by the person's interviewed.

Stereospecific inositol 1,4,5-[32P]trisphosphate binding to isolated rat liver nuclei: evidence for inositol trisphosphate receptor-mediated calcium release from the nucleus.

It is well known that inositol 1,4,5-trisphosphate binding and release of calcium are mediated by the same protein. Several reports have indicated the location of the inositol 1,4,5-trisphosphate receptor in organelles other than endoplasmic reticulum. Immunocytochemical studies on the subcellular localization of 1,4,5-trisphosphate receptor in the Purkinje cells from two laboratories have given contradictory results regarding the nuclear location of this receptor.

Phosphorylation by protein kinase C modulates agonist binding to striatal dopamine D2 receptors.

The effect of purified protein kinase C (PKC) on dopamine D2 receptor binding was studied. Saturation binding with [3H]spiperone was not affected. In competition experiments using agonists PKC-treated membranes showed a significant reduction in the proportion of high affinity sites, and the influence of GTP gamma S was abolished.

Rat liver nuclei protein kinase C is the isozyme type II.

Rat liver nuclei protein kinase C is identified as type II isozyme employing monospecific antibodies obtained against each three types of rat brain protein kinase C isozymes. (Yoshida, Y., Huang, F.