PubMed Health⌕ Search

Biomedical subjects

I Nalepa

Publications and source records attributed to I Nalepa.

At least 37 records · Page 2Linked to original sources
PubMed1992

Effects of diisopropyl fluorophosphate on muscarinic-M1-receptors and on receptor-mediated responsiveness of the phosphatidyl-inositol system in the cerebral cortex of rats.

The effects of acute and repeated treatments with an anticholinesterase (anti-ChE) compound, diisopropylfluorophosphate (DFP) on M1-acetylcholine receptor (M1-AChRs) density and on M1-mediated breakdown of inositol phospholipids were studied in the cerebral cortex of rats. The DFP doses induced an about 75% inhibition of cortical ChE 48 hr after the last treatment. The acute treatment did not change Bmax of M1-AChRs (measured as 3H-pirenzepine binding), while 1-week and 2-weeks treatments induced their significant down-regulation, by 14 and 29%, respectively. The responsiveness of M1-AChRs was measured in cortical prisms as accumulation of inositol phosphate (IP) following stimulation with a cholinergic agonist, carbachol (from 10 to 1000 microM). The IP accumulation (expressed as ratio stimulated/basal IP content) was lower in acute DFP rats than in controls at few carbachol concentrations, and after 2 weeks at most carbachol concentrations. This resulted in a significant increase of EC50. The data indicate the involvement of cortical phosphatidyl inositol system during intoxication by anti-ChE agents, namely a decreased efficiency of post-receptor mechanisms.

Animals↗
PubMed1991

Involvement of protein kinase C in the mechanism of in vitro effects of imipramine on generation of second messengers by noradrenaline in cerebral cortical slices of the rat.

Imipramine did not significantly inhibit the noradrenaline or isoproterenol-induced cyclic AMP accumulation in rat cerebral cortical slices, but inhibited the potentiation of this response by protein kinase C activator, a phorbol ester 12-O-tetradecanoyl-phorbol 13-acetate. In low concentrations (0.1-1 microM) it prevented the inhibitory effect of the phorbol ester on accumulation of inositol phosphate induced by noradrenaline, while in higher concentrations it inhibited the response by itself. Imipramine did not bind to beta-adrenoceptors but was an effective blocking agent of alpha 1-adrenoceptors (Ki = 38.1 nM). The data suggest that imipramine acts within the noradrenergic cyclic AMP generating system on two targets: inhibiting protein kinase C and blocking the alpha 1-adrenoceptor; both actions may reduce the alpha-adrenoceptor potentiation of beta-adrenoceptor-mediated cyclic AMP generation.

Adenylyl Cyclases↗
PubMed1991

Different mechanisms of beta-adrenoceptor down-regulation by chronic imipramine and electroconvulsive treatment: possible role for protein kinase C.

The aim of this study was to find out how protein kinase C (PKC) is involved in down-regulation of the beta-adrenoceptor in cortical slices of rats subjected to antidepressant treatments. The responses of the cyclic AMP generating system to forskolin, isoproterenol, and noradrenaline were tested in the absence and presence of a PKC activator, 12-O-tetradecanoylphorbol 13-acetate (TPA). The antidepressive treatments applied were chronic administration of imipramine and electroconvulsive shock. The potentiating effect of the phorbol ester on cyclic AMP response to isoproterenol was retained in imipramine-treated animals and even accentuated in rats subjected to electroconvulsive treatment; the TPA effect on noradrenaline-induced cyclic AMP response was blunted in rats receiving imipramine, but augmented in those receiving electroconvulsive treatment. In imipramine-treated rats the beta-down-regulation was still evident in the presence of TPA; after electroconvulsive treatment the phorbol ester-induced potentiation was so high that no significant beta-down-regulation could be observed. No procedure affected the response to forskolin. The beta-down-regulation that develops during chronic imipramine treatment differs from that caused by chronic electroconvulsive treatment; in both cases it is not related to the direct effect on adenylate cyclase.

Adenylyl Cyclases↗
PubMed1991

Avoidance learning during antidepressant withdrawal in mice.

Shuttle-box avoidance acquisition, locomotor activity and density of adrenoreceptors in the cerebral cortex have been evaluated, in CD-1 mice, during withdrawal from repeated treatment with desipramine or mianserin (5 or 14 daily injections of antidepressant drug, 10 mg kg-1). Withdrawal from mianserin did not produce any behavioural or neurochemical change. Mice withdrawn from desipramine exhibited avoidance facilitation, when training started 24 h (but not 72 or 120 h) after the last injection. Locomotor activity was not affected and no change was found in the density of beta-adrenoreceptors. An up-regulation of alpha 2- and, to a lesser extent, of alpha 1-adrenoreceptors, occurred 72 h following desipramine withdrawal. However, the assessment of the role played by these neurochemical changes in the avoidance facilitation observed during withdrawal from the antidepressant treatment requires further study.

Animals↗
PubMed1990

Second messengers: rate of formation as an index of receptor reactivity.

Generation of a second messenger upon stimulation of a metabotropic membrane receptor is the first biochemical reaction in the process of translation of a signal approaching the cell into the cellular response. Thus, the measurement of the rate of generation of these intracellular chemical signals may be a convenient way to assess the functional state of the receptor. The basic methodologies for assessment of the formation of cyclic AMP and inositol phosphates are described. Examples from our laboratory show how the measurement of these messengers may be employed in studies on receptor adaptation to permanently changed neurotransmitter availability, the discrepancy between the changes of receptor densities and functional up- or down-regulation, cooperativity of receptors, mechanisms of the action of drugs, neurotransmission changes in senescence and comparative neurochemistry.

Animals↗
PubMed1989

Increased responsiveness of the cerebral cortical phosphatidylinositol system to noradrenaline and carbachol in senescent rats.

The responsiveness of cerebral cortical alpha 1-adrenoceptors and cholinergic muscarinic M1 receptors was assessed in young (3 months) and aged (24 months) male Sprague-Dawley rats. The measure of responsiveness was the accumulation of inositol phosphate (IP) formed in [3H]myo-inositol-preloaded cerebral cortical slices in the presence of lithium, following stimulation with various concentrations of noradrenaline (1-300 microM) and carbachol (5-1000 microM). In old rats the maximum response to noradrenaline was higher by 80%, and that to carbachol by 33%, indicating an increased responsiveness of the investigated receptors in senescence.

Aging↗
PubMed1988

Reserpinization enhances electroconvulsive treatment effects on cortical alpha 1-adrenoceptors.

Repeated electroconvulsion shock (ECS) for 7 days given to mildly reserpinized rats strongly elevated the density of [3H]prazosin-labelled alpha 1-adrenoceptors and depressed the EC50 for norepinephrine-stimulated inositol phosphate accumulation, while the effects of either treatment given alone were small or negligible. Alterations in alpha 1-adrenoceptor activity caused by ECS could possibly be a function of receptor sensitivity during drug treatment.

Animals↗
PubMed1988

The influence of electroshock on adrenoceptor function in rat brain cerebral cortex: selectivity for the alpha-adrenoceptor site.

The present study was undertaken to examine the effect of electroshock on adrenoceptor-mediated cAMP and inositol phosphate accumulation in rat brain cerebral cortical slices. Under the conditions of these experiments, isoproterenol-induced cAMP accumulation was unaltered by electroshock, although there was a significant reduction in the norepinephrine- and isoproterenol + 6-fluoronorepinephrine-stimulated responses. No change in alpha-adrenoceptor-mediated inositol phosphate accumulation was noted. The results indicate that electroshock selectively modifies an alpha-adrenoceptor system in brain that differs from that associated with inositol phosphate accumulation.

Animals↗
PubMedDate not supplied

Haloperidol treatment selectively affects expression of Galpha(i)3 subunit mRNA in specific regions of the rat brain.

Relative abundance of GTP binding protein mRNA coding for subunits alpha(i)1, alpha(i)2 and alpha(i)3, and their changes induced with chronic blockade of D2 receptor by haloperidol were compared in the frontal cortex, striatum, hippocampus and cerebellar cortex of the rat using a specific method based on multiplex RT-PCR. Galpha(i) subtype 2 mRNA was the most abundant, followed by subtype 1 and subtype 3. The haloperidol treatment produced an area specific increase in Galpha(i)3 mRNA in the frontal cortex and a decrease of Galpha(i)3 in the striatum. After 8-day withdrawal period, haloperidol-induced,changes disappeared in the striatum but became accentuated in the frontal cortex. Changes in the relative expression of Galpha(i) subtypes may significantly influence long-lasting effects of chronic D2 receptor blockade.

Animals↗
PubMedDate not supplied

Adrenergic receptors' responsiveness after acute and chronic treatment with haloperidol in the presence of calcium channel blockade.

The effects of acute and chronic (14 days) treatment with haloperidol (0.5 mg/kg ip) given alone or 15 min after nifedipine (5 mg/kg ip) on responsiveness of the alpha1- and beta-adrenergic receptors was investigated ex vivo by measuring of the second messenger responses. The accumulation of inositol phosphate (IP) or cyclic AMP were measured in brain cortical slices challenged with noradrenaline or isoproterenol. The facilitatory effect of a single dose of haloperidol on IP accumulation (an increase by approximately 50%) was abolished by nifedipine pretreatment. After chronic treatment with haloperidol alone its facilitatory effect disappeared, but a treatment with haloperidol after nifedipine caused a significant increase in IP accumulation. No treatment affected the responses from beta-adrenoceptors. These data show that the action of chronically administered haloperidol may be changed by the concomitant calcium channel blockade that prevents development of adaptation to persistent presence of the drug.

Adrenergic alpha-Agonists↗
PubMedDate not supplied

Strain differences in changes in some parameters of cerebral cortical adrenergic system following chronic imipramine administration to rats.

The characteristics of [3H]prazosin binding sites in the membranes from cerebral cortex, the basal level of formation of cyclic AMP in cortical slices, and the responsiveness of the cyclic AMP generating system to noradrenaline and isoproterenol in this preparation were measured in Long-Evans, Wistar and Sprague-Dawley rats treated chronically with saline or imipramine. No differences between strains and treatments were observed regarding the Bmax and KD of [3H]prazosin binding sites. The basal levels of cyclic AMP formation were similar in control rats of all strains, but imipramine treatment augmented it significantly in Sprague-Dawley rats. The responses of the cyclic AMP generating system to noradrenaline were significantly lower in Long-Evans than in the remaining strains of rats. Only in Sprague-Dawley rats a significant downregulation of response to noradrenaline was observed after imipramine treatment. All three strains of rats differed significantly among themselves in their responsiveness to isoproterenol; only in Sprague-Dawley rats this response was down-regulated significantly (by 80%) by imipramine treatment.

Animals↗
PubMedDate not supplied

Differences in beta-adrenergic regulation of cyclic AMP formation in cerebral cortical slices of the rat and spiny mouse--Acomys cahirinus.

In both the rat and Acomys cahirinus the adrenergic cyclic AMP generating system in the brain is dependent not only on beta-, but also on alpha-adrenoceptors. The relative role of alpha-adrenoceptors is much greater in the Acomys cahirinus. This feature makes the Acomys an interesting animal model for investigating the role of alpha-beta-adrenoceptor coupling in generation of cyclic AMP and the mechanism of action of antidepressant treatment.

Adrenergic alpha-Agonists↗