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Biomedical subjects

A Reches

Publications and source records attributed to A Reches.

At least 73 records · Page 4Linked to original sources
PubMed1982

The effect of chronic L-dopa administration on supersensitive pre- and postsynaptic dopaminergic receptors in rat brain.

Chronic administration of haloperidol induced supersensitivity of the pre- and postsynaptic dopaminergic receptors in rat brain. The response of the presynaptic receptors was determined by an enhanced inhibitory effect of apomorphine on dopamine synthesis after gamma-butyrolactone injection. This change in the receptor function was detected both in the nigrostriatal and mesolimbic pathways. Haloperidol also increased the 3H-spiperone binding sites in striatal membranes, indicating supersensitivity of the postsynaptic receptors. Subsequent prolonged treatment with high doses of L-DOPA/carbidopa resulted in a decrease in 3H-spiperone binding sites, but had no effect on the supersensitive presynaptic receptors. It is suggested that tardive dyskinesia may be a state of both pre- and postsynaptic dopamine receptor supersensitivity and that chronic L-DOPA treatment may have a differential effect on these sites.

Animals↗
PubMed1982

3-O-methyldopa blocks dopa metabolism in rat corpus striatum.

3-O-Methyldopa (OMD) given to rats inhibits striatal uptake and utilization of L-dopa. Thus, the accumulation of L-dopa, dopamine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid in OMD-pretreated rats after L-dopa injection is significantly lower compared with control rats. This effect of OMD is dose-dependent. OMD inhibits L-dopa accumulation in the striatum after inhibition of aromatic amino acid decarboxylase activity with 3-hydroxybenzylhydrazine-HCL. This effect is not mediated through inhibition of firing in dopaminergic neurons, since the accumulation of dopamine in the striatum after gamma-butyrolactone injection was also significantly reduced by OMD. It is suggested that OMD competes with L-dopa and tyrosine uptake into the brain. These findings are in line with clinical observations which indicate that high plasma levels of OMD in parkinsonian patients are associated with poor response to L-dopa. The data presented here indicate that use of catechol-O-methyltransferase inhibitors with L-dopa may be of value in the treatment of parkinsonian patients.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

Catechol-O-methyltransferase inhibition by U-0521 increases striatal utilization of levodopa.

The effects of U-0521, a catechol-O-methyltransferase (COMT) inhibitor, were studied on this enzyme activity and on Dopa metabolism in rat striatum. In vivo maximal inhibition (95%) of COMT activity was obtained at 5 min with enzyme recovery to 64% of basal activity at 120 min. When injected in increasing doses U-0521 (200 mg . kg-1) inhibited, at 10 min, COMT activity by 85% with an IC50 = 80 mg . kg-1. In rats pretreated with U-0521 and then with DOPA the accumulation of 3-O-methyldopa-(OMD) in the plasma was essentially blocked while Dopa, dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) accumulation in the striatum was significantly higher than in DOPA treated controls. U-0521, a potent COMT inhibitor, enhances the availability and utilization of levodopa in the brain and may thus be helpful in future treatment of parkinsonian patients.

Animals↗
PubMed1982

Inhibition by lithium of PGE1-sensitive adenylate cyclase in neuroblastoma X glioma hybrid cells: approach to the attenuation of the opiate withdrawal syndrome.

Exposure of neuroblastoma X glioma hybrid cells to LiCl (Li+) for 48 h significantly reduces prostaglandin E1 (PGE1)-dependent cyclic adenosine monophosphate (AMP) accumulation. When applied simultaneously with morphine for the same period, Li+ inhibits the excessive accumulation of cyclic AMP in response to PGE1 characteristically exhibited by these cells upon opiate withdrawal. Likewise, Li+ inhibits, in vitro, PGE1-dependent cyclic AMP accumulation in tissue slices from rat corpus striatum. Prophylactic administration of Li+ in the diet attenuates the withdrawal symptoms in morphine-addicted rats. These findings support clinical reports that suggest that prophylactic treatment with Li+ attenuates the severity of the opiate withdrawal syndrome.

Adenylyl Cyclase Inhibitors↗
PubMed1980

Do human platelets have opiate receptors?

In their study of prostaglandin E1 (PGE1)-sensitive adenylate cyclase (AC) in rat brain homogenates, Collier and Roy claimed that the activity of this enzyme is inhibited by opiates. They also proposed that opiates exert their analgesic and allied effects by inhibiting AC of neurones that are normally stimulated by E prostaglandins. Studies using neuroblastoma x glioma hybrid cells supported this hypothesis. However, subsequent studies with mammalian brain and rat brain tissue slices yielded conflicting results. PGE1 also inhibits platelet aggregation, probably through activation of platelet AC. Gryglewski et al. showed that morphine inhibits the anti-aggregating effect of PGE1 on ADP- and adrenaline-induced platelet aggregation, and suggested that the inhibition by morphine is mediated through platelet AC activity. We report here our attempts to reproduce the results of Gryglewski et al. and our examination of the effect of morphine on PGE1-sensitive AC activity in platelet lysates and on PGE1-induced accumulation of cyclic AMP in intact platelets. The possible existence of opiate receptors in platelets was also assessed by direct binding studies with 3H-etorphine. In contrast to Gryglewski et al., we could not detect any effect of opiates on the aggregation of human platelets, nor did we find any other evidence supporting the presence of opiate receptors in these cells. Thus we conclude that the presence of opiate receptors in human platelets is unlikely.

Adenylyl Cyclases↗
PubMed1980

Thick filament degeneration in a case of acute quadriplegia.

Absence of thick filaments from the A bands in tissue giving apparently normal histochemical reactions for myosin ATPase, was seen in a case of acute onset muscle weakness progressing rapidly to quadriplegia with cerebral involvement. There was also widespread degeneration of interstitial structures and much phagocytosis. The dissociation of structure and function of the thick filaments suggests that a selective injury occurred within the myosin molecule. The etiology of the condition although clinically suggestive of a polyneuropathy remains pathologically uncertain. Toxic, immunological or viral causation may be responsible.

Adenosine Triphosphatases↗
PubMed1979

The anatomic basis of visual agnosia.

In a patient with associative visual agnosia without alexia, there was bilateral infarction in the distribution of the posterior cerebral arteries, with corticosubcortical lesions in both occipitotemporal regions, sparing the corpus callosum. Bilateral loss of visual-limbic connections may underlie associative visual agnosia, and bilateral lesions of the inferior longitudinal fasciculi may be the necessary and sufficient lesions for this syndrome. Alexia was absent in this case, perhaps because the corpus callosum was intact.

Agnosia↗
PubMed1979

Heparin inhibits PGE1-sensitive adenylate cyclase and antagonizes PGE1 antiaggregating effect in human platelets.

PGE1-sensitive adenylate cyclase in human platelet lysates in inhibited (50%) by heparin (10 microgram/ml). Inhibition is of a mixed type when analyzed by double-reciprocal analysis. It is also shown that heparin (2.5 to 10 microgram/ml) effectively antagonizes the antiaggregating effect of PGE1 on ADP-induced platelet aggregation. The possibility that heparin may exert its platelet-aggregating activity through inhibition of PGE1-sensitive AC in human platelets is discussed.

Adenylyl Cyclase Inhibitors↗
PubMed1978

Modulation of adenylate cyclase activity by sulfated glycosaminoglycans. II. Effects of mucopolysaccharides and dextran sulfate on the activity of adenylate cyclase derived from various tissues.

Heparin was found to be the most potent inhibitor of rat ovarian luteinizing hormone-sensitive adenylate cyclase (I50 = 2 microgram/ml) when compared to other naturally occurring glycosamin oglycans. This inhibition was also apparent when this enzyme was stimulated by follicle-stimulating hormone or prostaglandin E2. Heparin was also found to inhibit glucagon-sensitive rat hepatic adenylate cyclase, and the prostaglandin E1-sensitive enzyme from rat ileum and human platelets. In contrast, heparin stimulated the dopamine sensitive adenylate cyclase from rat caudate nucleus. The sulfated polysugar dextran sulfate exerts similar effects on adenylate cyclase activity of the rat ovary and was shown to inhibit hormone binding to rat ovarian plasma membrane in a manner similar to that exerted by heparin. In contrast to heparin, dextran sulfate inhibited dopamine-sensitive adenylate cyclase from rat caudate nucleus.

Adenylyl Cyclases↗