PubMed Health⌕ Search

Biomedical subjects

I Nalepa

Publications and source records attributed to I Nalepa.

44 records · Page 3Linked to original sources
PubMedDate not supplied

Different calcium requirements during incorporation of myo-inositol into membrane lipids for phosphatidylinositol hydrolysis stimulated by carbachol and noradrenaline.

Stimulation of phosphatidylinositol hydrolysis by noradrenaline requires the presence of calcium in the medium during the whole incubation and preincubation procedure, while carbachol-induced inositol phosphate formation is equally efficient in calcium-free and calcium-containing medium. This finding confirms the notion that phosphatidylinositols mobilized after stimulation of various receptors are present in different metabolic pools: the pool mobilized by alpha 1 adrenoceptors is apparently formed from myo-inositol incorporated into membrane phospholipids by a calcium-dependent process.

Analysis of Variance↗
PubMedDate not supplied

The effect of psychotropic drugs on the interaction of protein kinase C with second messenger systems in the rat cerebral cortex.

The paper describes and compares the influences of the antidepressants (imipramine, mianserin, citalopram), electroconvulsive shock, and the neuroleptics (haloperidol, chlorpromazine and spiperone) on the systems of second messengers related to adrenergic receptors in rat cerebral cortex, measured by generation of cyclic AMP and inositol phosphate (IP), and their influence on the effects of activation of protein kinase C (PKC) by its synthetic activator, phorbol ester (TPA). The effect of PKC-stimulation was expressed as a reduction of noradrenaline-stimulated IP accumulation and, on the other hand, as an enhancement of cyclic AMP response under stimulation with noradrenaline and isoproterenol. When administered chronically, the described antidepressants (unlike the neuroleptics) augmented IP accumulation or left it unchanged, but they reduced PKC's negative feedback with the alpha 1-adrenoceptor. PKC-induced potentiation of cyclic AMP's response to beta-adrenergic receptor stimulation was unchanged or enhanced, while the antidepressants reduced the generation of this second messenger. However, citalopram increased cyclic AMP generation and reduced PKC potentiation. Taking into account the role of PKC in adrenergic receptors cross-talk explains why, despite antagonization of alpha 1-adrenoceptors and induction of beta down-regulation by some antidepressants, enhancement of the process of noradrenergic neurotransmission can occur as a final effect of the action of these drugs. It was found that the action of antidepressants is largely related to the adrenergic system, even when their action on this system is not direct and is accomplished by their influence on another neurotransmitting system, e.g. the serotonergic system.

Animals↗
PubMedDate not supplied

The antagonistic effect of separate and consecutive chronic treatment with imipramine and ECS on the inhibition of alpha 1-adrenoceptor activity by protein kinase C.

We tested how chronic antidepressant treatments (chronic imipramine, chronic electroconvulsive shock (ECS) and chronic ECS given after chronic imipramine) affect the feedback inhibition of alpha 1-adrenoceptor activity (measured with inositol phosphate (IP) accumulation after stimulation with noradrenaline). The inhibitory effect of a 12-O-tetradecanoylphorbol 13-acetate (TPA) on IP response was found to be due to protein kinase C (PKC) activation, as it was abolished by specific protein kinase inhibitors, staurosporine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7). Chronic ECS completely abolished the inhibition by TPA of inositol phosphate response to noradrenaline, while chronic imipramine reversed the feedback and led to potentiation of responses by TPA to intermediate concentrations of noradrenaline. Subsequent chronic ECS abolished the imipramine-induced reversal of TPA inhibition and lead to the changes similar as observed after ECS alone. The present results may suggest why in some cases, in which imipramine therapy is ineffective, subsequent ECS may be clinically beneficial.

Adrenergic alpha-1 Receptor Antagonists↗
PubMedDate not supplied

The effects of chlorpromazine and haloperidol on second messenger systems related to adrenergic receptors.

The aim of this study was to investigate the binding of chlorpromazine and haloperidol to rat cerebral cortical adrenoceptors and to assess their effect on responsiveness of alpha 1- and beta-adrenoceptors measured by accumulation of second messengers, inositol phosphate and cyclic AMP, after stimulation with noradrenaline and isoproterenol. The effect of neuroleptics on protein kinase C was assessed by carrying out incubations in the absence and presence of the phorbol ester, 12-O-tetradecanoyl-phorbol 13-acetate (TPA). The effects of chronic administration of haloperidol (0.5 mg/kg/d for 14 days) on responses of second messenger systems to noradrenaline and isoproterenol in the presence and absence of TPA were also measured. The results indicate that in vitro chlorpromazine and haloperidol similarly inhibit noradrenaline-induced responses of inositol phosphate and cyclic AMP, but differently affect the potentiation of these responses by protein kinase C: the inhibitory effect of haloperidol, but not that of chlorpromazine was prevented by TPA. Similarly, only chlorpromazine inhibited the cyclic AMP responses to isoproterenol. The differences between the effects of chlorpromazine and haloperidol may be explained by their different affinity to various subtypes of adrenoceptor. In a chronic experiment haloperidol did not induce changes in responsiveness of cortical alpha 1- and beta-adrenoceptors, but inhibited TPA-induced potentiation of cyclic AMP responses.

Animals↗
PubMedDate not supplied

Phorbol ester and central chemosympathectomy augment beta-adrenoceptor response by different mechanisms.

The aim of this study was to compare the mechanisms of increased responsiveness of the beta-adrenoceptor dependent cyclic AMP generating system induced by chronic decrease of noradrenaline availability (beta-upregulation) with that resulting from simultaneous stimulation of alpha-adrenoceptors (alpha-potentiation) and to assess the role of protein kinase C in these phenomena. The beta-upregulation was produced by central chemosympathectomy with 6-hydroxydopamine. The role of alpha 1- and alpha 2-adrenoceptors was assessed by comparison of the effects of specific beta-adrenoceptor agonist isoproterenol with those of a mixed alpha-beta-adrenoceptor agonist noradrenaline, and clonidine was used to selectively stimulate alpha 2-adrenoceptors. The role of protein kinase C was assessed by measuring cyclic AMP responses in the presence and absence of 12-O-tetradecanoyl-phorbol 13-acetate. The results indicate that the mechanism of increased responsiveness induced by central chemosympathectomy is different from the alpha-potentiation, that only alpha 1-adrenoceptors are involved positively in alpha-potentiation, while the alpha 2-adrenoceptors play an inhibitory role, and that increased responsiveness following central chemosympathectomy may be inhibited by protein kinase C activation.

Animals↗
PubMedDate not supplied

The effect of calcium channel blockade on the action of chronic ECT and imipramine on responses of alpha 1- and beta-adrenoceptors in the rat cerebral cortex.

Chronic co-administration of nifedipine and ECT or imipramine results in an increase in responsiveness of cerebral cortical alpha 1-adrenoceptors as measured by accumulation of inositol phosphate in cortical slices after noradrenaline stimulation; the responsiveness of beta-adrenoceptor, measured by accumulation of cyclic AMP, was depressed similarly by antidepressant treatment with and without nifedipine.

Animals↗
PubMedDate not supplied

Modulation of electroconvulsive treatment induced beta-adrenergic down-regulation by previous chronic imipramine administration: the involvement of protein kinase C.

To test how previous treatment with imipramine affects the action of electroconvulsive shock (ECS) on cortical beta-adrenergic system, male Wistar rats received imipramine, 10 mg/kg b.i.d. for two weeks, followed by 8 days of ECS, and 24 h after the last shock the responsiveness of beta-adrenoceptor system was tested by measuring cyclic AMP formation in cortical slices after exposure to noradrenaline or isoproterenol. To assess the possible role of protein kinase C, the same responses were measured in the presence of a protein kinase C activator, 12-O-tetradecanoyl-phorbol 13-acetate (TPA). ECS alone was found more effective in inducing beta-adrenergic-down-regulation than imipramine, and tended to produce stronger effect when given after chronic imipramine. In contrast to imipramine, which effectively inhibited TPA-induced potentiation of the action of isoproterenol, ECS strongly facilitated it. However, administrated after chronic treatment with imipramine, ECS did not change the potentiation. The results suggest that effects of ECS are slightly modified, but not inhibited by previous administration of imipramine.

Adrenergic beta-Agonists↗