Search PubMed⌕ Search

Biomedical subjects

A Szmigielski

Publications and source records attributed to A Szmigielski.

At least 19 recordsLinked to original sources
PubMed1997

The effect of prolonged imipramine treatment on the alpha 1-adrenoceptor-induced translocation of protein kinase C in the central nervous system in rats.

The aim of the study was to investigate the effects of prolonged treatment with imipramine (10 mg kg-1/day i.p. for 21 days) on the translocation of protein kinase C (PKC) after stimulation of the alpha 1-adrenoceptor. Methoxamine (5-50 mg kg-1) and phenylephrine (0.1-1 mg kg-1) induced a rapid and long-term redistribution of PKC from the cytosolic to the membrane fraction in the rat frontal cortex and hippocampus. The effects of methoxamine and phenylephrine were completely blocked by pretreatment with prazosin. Prolonged pretreatment with imipramine changed the response of PKC to methoxamine and phenylephrine. Much lower doses of alpha 1-adrenoceptor agonists were able to induce the redistribution of PKC. Moreover, prolonged treatment with imipramine markedly increased the basal activity of PKC in the membrane fractions of the frontal cortex and hippocampus.

Animals↗
PubMed1997

The cooperation between the influx of extracellular calcium and alpha1-adrenoceptor-induced translocation of protein kinase C.

Calcium ionophore A23187 or phenylephrine injected i.p. in doses of 0.05-0 .25 mg kg-1 and 0.1-1 mg kg-1, respectively, induced translocation of protein kinase C (PKC) from the cytosol to the membrane fraction of the rat frontal cortex and hippocampus. The action of A23187 was blocked in a dose-dependent manner by nifedipine and verapamil. The phenylephrine induced translocation of PKC was blocked by prazosin and in a dose-dependent manner by nifedipine and verapamil. In contrast, pre-treatment with a small, ineffective by itself, dose of A23187 (0.02 mg kg-1) potentiated the alpha1-adrenoceptor induced translocation of PKC. Thus, it seems that the influx of calcium ions through an L-type calcium channel is probably necessary for a full alpha1-adrenoceptor mediated activation and translocation of PKC.

Adrenergic alpha-Agonists↗
PubMed1992

Regulation of protein kinase C after stimulation of alpha 1-adrenoceptors in rat hippocampus.

Endogenous inhibitor of protein kinases (type II inhibitor, GABA-modulin) blocks the phosphorylation catalyzed by cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) as a competitive inhibitor of substrate proteins when histone is used as a substrate. Moreover, type II inhibitor blocks the phosphorylation of endogenous membrane proteins by PKC. Stimulation of alpha 1-adrenoceptors induced rapid redistribution of PKC from cytosol to membrane fraction which lasted at least 3 h, accompanied by rapid and short-lasting translocation of type II inhibitor from membrane to cytosol fraction. The cytosol content of type II inhibitor reached maximal level 10 and 20 min and became normal again 40 min after i.p. administration of methoxamine. The above actions of methoxamine were completely blocked by pretreatment with prazosin. It seems that short-lasting redistribution of type II inhibitor from membrane to cytosol fraction allows the effective phosphorylation of membrane proteins by PKC after stimulation of alpha 1-adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1991

Cooperation between D1- and D2-dopamine receptors in the nucleus accumbens.

Apomorphine, used in small doses (20-50 micrograms/kg), induced an increase in the activity of an endogenous inhibitor of cAMP dependent protein kinases (Walsh inhibitor, type I inhibitor) in nucleus accumbens of the rat. The action of apomorphine was blocked by sulpiride and aminophylline and enhanced by SCH-23390. Pretreatment with 6-OH-dopamine resulted in a shift of the dose-response curve for apomorphine to the left, suggesting supersensitivity of D2 receptors. Moreover, stimulation of D2 receptors induced a decrease in phosphorylation of DARPP-32, a specific protein, located in neurones containing D1 receptors. Large doses of apomorphine (over 0.5 mg/kg) provoked a decrease in type I inhibitor activity, blocked by SCH-23390 and enhanced by sulpiride and aminophylline. Moreover, SCH-23390 blocked a decrease in type I inhibitor activity induced by large doses of sulpiride and sulpiride blocked an increase in type I inhibitor activity produced by large doses of SCH-23390. The results suggest that D1 and D2 receptors in the nucleus accumbens could cooperate with the same adenylate cyclase and could be located on the same neurones.

Animals↗
PubMed1986

Effect of repeated electroconvulsive shocks on isoprenaline-induced changes of the endogenous inhibitor of cAMP-dependent protein kinase in rat brain.

The effect of repeated electroconvulsive shocks (ECS) on the responsiveness to isoprenaline of an endogenous, specific inhibitor of cAMP-dependent protein kinase (type I inhibitor) was tested in rat hippocampus and brainstem. Isoprenaline produced a dose-dependent decrease in the type I inhibitor activity in these brain structures. Neither the basal activity nor the isoprenaline-induced changes of type I inhibitor activity were affected by a single ECS. However, a series of 11 ECS markedly reduced the response of the type I inhibitor activity to isoprenaline. The action of isoprenaline was completely blocked by propranolol and markedly enhanced by aminophylline. The results indicate that the subsensitivity of beta-adrenoceptors is accompanied by reduced responsiveness of type I inhibitor activity to isoprenaline.

Animals↗
PubMed1986

Changed sensitivity of alpha 2-adrenoceptors mediating a decrease in protein kinase inhibitor activity in the brain of vasopressin-hypertensive rats.

Clonidine produced an increase of cGMP content and a decrease of the endogenous type II inhibitor of protein kinase in rat hypothalamic slices. When administered to rats, the effect of clonidine on type II inhibitor activity in the hypothalamus and brain-stem depended on the dose. Low doses (10-50 micrograms X kg-1 i.p.) produced an increase, probably by stimulating presynaptic alpha 2-adrenoceptors, whereas large doses (200-1000 micrograms X kg-1 i.p.) produced a decrease of type II inhibitor activity by stimulating postsynaptic receptors. The development of vasopressin hypertension was associated with a gradual reduction of the response of the type II inhibitor to low and high doses of clonidine. In vasopressin-hypertensive rats neither small nor large doses of clonidine were able to induce changes in type II inhibitor activity suggesting subsensitivity of pre- and postsynaptic alpha 2-adrenoceptors. However, clonidine appeared to be equally effective in blocking electrically stimulated [3H]noradrenaline release from hypothalamic slices of vasopressin-hypertensive and control, normotensive rats. Reduced reactivity of postsynaptic alpha 2-adrenoceptors seems to be of great importance since treatment of vasopressin-hypertensive rats with 6-hydroxydopamine resulted in a decrease of blood pressure and reappearance of the sensitivity of postsynaptic alpha 2-adrenoceptors to clonidine.

Animals↗
PubMed1986

Isoprenaline-induced changes in activity of the endogenous inhibitor of cAMP-dependent protein kinases under conditions of beta-adrenoceptor supersensitivity.

Isoprenaline-induced changes in activity of an endogenous, specific inhibitor of cAMP-dependent protein kinases (type I inhibitor) under conditions of experimental supersensitivity of beta-adrenoceptors were investigated in rat hippocampus and brain stem. Both subchronic administration of reserpine (2.5 mg kg-1, i.p., 4 days, once daily) and i.c.v injections of 6-hydroxydopamine (250 micrograms/ventricle, bilaterally, 48 h apart), which are known to increase beta-adrenoceptor sensitivity in the rat brain, markedly enhanced the response of the type I inhibitor activity to isoprenaline. To obtain a significant decrease of type I inhibitor activity in the examined brain structures of these animals, doses of isoprenaline 2-5 times lower than in control groups had to be used. It is suggested that the isoprenaline-induced decrease of type I inhibitor activity might be used as an index of central beta-adrenoceptor reactivity in-vivo.

Animals↗
PubMed1984

The effect of stimulation of pre- and postsynaptic dopamine receptors on the endogenous inhibitor of cAMP-dependent protein kinase.

The effect of various doses of apomorphine on the activity of specific endogenous inhibitor of cAMP dependent protein kinase (type I inhibitor) was studied. Apomorphine produced biphasic changes in the type I inhibitor activity in rat striatum. Small doses (50-100 micrograms/kg) induced an increase while large doses (0.5-10 mg/kg) caused a dose dependent decrease of the type I inhibitor activity. The apomorphine induced increase in type I inhibitor activity was completely blocked by small, presynaptically active doses of haloperidol and chlorpromazine and by aminophylline. This suggests that small doses of apomorphine stimulate presynaptic dopamine D2-receptors. In contrast, the apomorphine induced decrease of the type I inhibitor activity was greatly potentiated by aminophylline and by presynaptically active doses of the neuroleptics, suggesting a postsynaptic site of action for large doses of apomorphine. Determination of the type I inhibitor activity is proposed as one of the biochemical tests allowing to recognize the site of action of drugs stimulating dopamine receptors.

Aminophylline↗
PubMed1984

Effect of supersensitivity of pre- and postsynaptic dopamine receptors on the activity of endogenous inhibitor of cAMP dependent protein kinase in rat striatum.

Small presynaptically active doses of apomorphine (50-100 micrograms/kg) induced an increase, while large doses (1-10 mg/kg) provoked a decrease of type I inhibitor activity in rat striatum. Supersensitivity of postsynaptic D1 receptors was produced in rats by i.c.v. injection of 6-hydroxydopamine (6-OH-DA) and supersensitivity of presynaptic dopamine autoreceptors by i.p. administration of reserpine (1 mg/kg daily for 4 days). In reserpine pretreated rats apomorphine produced an increase in type I inhibitor activity after about 5 times lower doses than in control rats. This effect of apomorphine was blocked by aminophylline and by presynaptically active doses of haloperidol. In 6-OH-DA pretreated rats small doses of apomorphine did not change the type I inhibitor activity. The apomorphine induced decrease of type I inhibitor activity was seen after about 10 times lower doses of apomorphine than in control rats. This action of apomorphine was blocked by postsynaptically active doses of haloperidol and enhanced by aminophylline. The obtained results show that supersensitivity of presynaptic D2 dopamine autoreceptors and postsynaptic D1 receptors is accompanied by changes in the reactiveness of type I inhibitor activity to apomorphine.

Aminophylline↗
PubMed1981

Modulation of the activity of endogenous protein kinase inhibitors in rat heart by the beta adrenergic receptor.

The rat heart contains a large amount of two protein kinase inhibitors. The type I inhibitor blocks the activity of cAMP-dependent protein kinase while the type II inhibitor blocks cGMP-dependent protein kinase, cAMP-dependent protein kinase and cyclic nucleotide-independent protein kinase. Isoproterenol produced a dose-dependent decrease of the type I inhibitor activity and an increase of cAMP content in rat heart. The decrease of the type I inhibitor activity is mediated through adrenergic beta receptor because propranolol and practolol but not phentolamine prevented the effects of isoproterenol. Moreover, prior treatment with aminophylline markedly enhanced isoproterenol-induced increase of cAMP content and decrease of the type I inhibitor activity. Isoproterenol did not change the activity of the type II inhibitor. These results are compatible with the hypothesis that the neurotransmitter generated cAMP modulates phosphorylation in the heart by changing the relationship between cAMP-dependent protein kinase and the type I inhibitor activity.

Aminophylline↗
PubMed1979

Action of harmaline and diazepam on the cerebellar content of cyclic GMP and on the activities of two endogenous inhibitors of protein kinase.

The rat cerebellum contains a significant amount of cGMP-dependent protein kinase, cAMP-dependent and cyclic nucleotide-independent protein kinase, and a large concentration of protein kinase inhibitors. These inhibitors are thermostable proteins which can be separated by gel chromatography into two molecular forms: the type 1 and type 2 inhibitors of protein kinase (14). The type 1 inhibitor blocks the rat cerebellar cAMP-dependent protein kinase activity while the type 2 inhibitor blocks the cGMP-dependent protein kinase, the cAMP-dependent protein kinase, and the cyclic nucleotide-independent protein kinases. The activity of the type 2 inhibitor increased or decreased in opposite direction to changes of cerebellar cGMP content generated by injection of 10 mg/kg harmaline 2.5 mg diazepam. No changes of type 1 inhibitor were observed under these conditions. The drug-induced shift of type 2 inhibitor of protein kinase was not mediated by changes in protein synthesis because it persisted after pretreatment with cycloheximide. These results are compatible with the hypothesis that cGMP modulates phosphorylation in cerebellum by changing the relationship between cGMP-dependent protein kinase and type 2 inhibitor content.

Alkaloids↗
PubMed1977

Endogenous protein kinase inhibitors. Purification, characterization, and distribution in different tissues.

A thermostable inhibition of ATP-protein phosphotransferase (EC 2.7.1.37) (protein kinase) which is present in crude tissue extracts has been resolved by gel chromatography (Sephadex G-100) into two molecular forms. These two forms will be referred to as type I and type II inhibitor. The type I inhibitor (Mr approximately or equal to 24,000) is specific for cAMP-dependent protein kinase and corresponds to the inhibitor described earlier (Walsh, D. A., Ashby, C. D., Gonzalez, C., Calkins, D., Fisher, E. H., and Krebs, E. G. (1971) J. Biol. Chem. 246, 1977-1985). The type II inhibitor (Mr approximately or equal to 15,000) competes for the enzyme with various substrate proteins (histone, alpha-casein, and Leu-Arg-Arg-Ala-Ser-Leu-Gly (kemptide). The type II inhibitor blocks protein phosphorylation catalyzed by several types of protein kinases (cAMP- and cGMP-dependent or cyclic nucleotide-independent protein kinases). The type II inhibitor from rat brain has been purified 1500-fold; this protein is thermostable, has acidic characteristics, and does not require Ca2+ ions for its activity. Different ratios and concentrations of type I and type II inhibitors of protein kinase are found in rat skeletal muscle, pancreas, cerebellum and corpus striatum, and in lobster tail muscle.

Animals↗