Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have employed a molecular biological approach to study the dynamic status of hippocampal opioid peptides in response to seizures elicited by different experimental models, such as electroconvulsive shocks (ECS) and amygdaloid kindling. Both ECS- and kindling-induced seizures triggered an initial large release of enkephalin and dynorphin, but produced opposite long-term effects on the biosynthesis of these two peptides, an increase of enkephalin, and a drastic decrease of dynorphin. Electrical stimulation of the perforant pathway produced differential changes of enkephalin and dynorphin, which were identical to those of ECS and kindling. This finding confirmed our hypothesis that the perforant pathway was responsible for the mediation of ECS- and kindling-induced changes in opioid peptide turnover. Strongest evidence indicating a role for opioid peptides in mediating the expression of seizure-related behaviors was found using the kainic acid model, where we saw that hippocampal enkephalin was essential to the expression of kainic acid-induced wet dog shakes (a preconvulsive shaking behavior). Furthermore, it was found that the granular-mossy fiber pathway of the ventral, but not the dorsal, hippocampus was essential for the expression of this shaking behavior. However, destruction of the granular-mossy fiber pathway potentiated the seizures and hippocampal cell loss induced by kainic acid. This unexpected, yet extremely interesting, finding not only distinguished the roles of the granular-mossy fiber pathway in mediating wet dog shakes vs. convulsive seizures, but also challenged the dogma that this granular-mossy fiber pathway is essential for the expression of limbic seizures.
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PMID:Hippocampal opioid peptides and seizures. 136 30

Treatment of common marmosets with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 1-4 mg/kg for up to 4 days) caused a profound parkinsonian state. Ten days from the start of MPTP treatment, all animals showed marked motor impairment, consisting of bradykinesia and akinesia, limb rigidity, postural abnormalities, loss of vocalisation and blink reflex, and, on occasions, postural tremor. Measurement of caudate-putamen monoamine content at this time showed a profound loss in 3,4-dihydroxyphenylethylamine, homovanillic acid, and 3,4-dihydroxyphenylacetic acid concentrations. Measurement of neuropeptide concentrations in the caudate-putamen, internal and external segments of the globus pallidus, nucleus accumbens, substantia nigra, frontal cortex, and hippocampus showed met-enkephalin, leu-enkephalin, and cholecystokinin (CCK-8) concentrations to be unaffected by MPTP treatment. There was a small decrease in the substance P content of frontal cortex, but otherwise the content of this neuropeptide was unaltered. Parkinsonism in the marmoset, induced by MPTP treatment 10 days earlier, does not alter neuropeptide concentrations in the manner observed in Parkinson's disease.
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PMID:Lack of change in basal ganglia neuropeptide content following subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment of the common marmoset. 242 37

Kainic acid (KA), an excitatory neurotoxin, was used as a tool to study the metabolism of hippocampal opioid peptides and their functional role in the expression of wet-dog shakes (WDS). A single intracerebral injection of KA (1 microgram/rat) caused recurrent motor seizures lasting 3-6 h. During the convulsive period, native Met5-enkephalin-like (ME-LI) and dynorphin A(1-8)-like (DYN-LI) immunoreactivities in hippocampus decreased by 31 and 63%, respectively. By 24 h after dosing, the hippocampal opioid peptides had returned to control levels, and by 48 h ME-LI had increased 270% and DYN-LI 150%. Immunocytochemical analysis revealed that ME-LI and Leu5-enkephalin-like (LE-LI) immunostaining in the mossy fibers of dentate granule cells and the perforant-temporoammonic pathway had decreased visibly by 6 h and had increased markedly by 48 h following KA. A visible decrease in DYN-LI in mossy fiber axons within 6 h was followed by a substantial increase at 48 h. To determine whether the increases in hippocampal ME-LI reflected changes in ME biosynthesis, levels of mRNA coding for preproenkephalin (mRNAenk) and cryptic ME-LI cleaved by enzyme digestion from preproenkephalin were measured. Following the convulsive period (6 h), mRNAenk was 400% of control, and by 24 h, cryptic ME-LI was 300% of control. Increases in native and cryptic ME-LI and in mRNAenk were also noted in entorhinal cortex, but not in hypothalamus or uninjected striatum. Our data suggest that KA-induced seizures cause an increase in ME release, followed by a compensatory increase in ME biosynthesis in the hippocampus and entorhinal cortex. Several lines of evidence from this study have suggested that hippocampal enkephalins are intimately related to KA-elicited WDS. The shaking behavior was attenuated by pretreatment with naloxone or antisera against [Met5]-enkephalin. We also observed that KA-induced WDS can be mimicked by intrahippocampal injection of enkephalin-related peptides. Furthermore, this study demonstrated that intact dentate granule cells are essential for KA- and enkephalin-induced WDS, since a colchicine injection into the ventral hippocampus, which selectively destroys granule cells, abolished this behavior.
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PMID:Kainic acid as a tool to study the regulation and function of opioid peptides in the hippocampus. 289 Feb 24

Administration of the drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induces a parkinsonian syndrome in primates. Intraperitoneal injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the common marmoset (Callithrix jacchus) produced symptoms of rigidity, akinesia and tremor which persisted for at least one month. However, after this time, considerable behavioural recovery occurred, although animals were still severely bradykinetic compared with controls. Marmosets were allowed to survive for 1, 3 1/2 or 7 months prior to histological and immunocytochemical analysis. Detection of catecholaminergic neurons using antibodies directed against the enzyme tyrosine hydroxylase revealed a profound (80%) loss of dopaminergic cells from the substantia nigra one month after initiation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment. This was accompanied by a severe gliosis. Fewer cells were lost from the adjacent ventral tegmental area (45%), but dopamine-containing cells in other brain areas were not obviously affected. At longer survival times the substantia nigra was less damaged, with a proliferation of glia in the pars compacta and a loss of approximately 20% of the dopaminergic perikarya. Using immunohistochemical techniques, the distribution of neuropeptides substance P, [Met]enkephalin and dynorphin 1-17-like immunoreactivity were examined and found to exhibit distinctive patterns in the marmoset substantia nigra. The integrity of these systems appeared intact at all times after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment. These results support the hypothesis that the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine produces a clinical syndrome, indistinguishable from Parkinson's disease, via a selective destruction only of neurons with perikarya in the substantia nigra pars compacta and the ventral tegmental area. The findings that the peptidergic input to these cells together with most non-nigral dopaminergic cell groups are not damaged, indicate that the selectivity of the lesion produced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine appears greater than that seen in idiopathic Parkinson's disease. The neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the marmoset may not be permanent since both behavioural and biochemical recovery were observed after several months.
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PMID:An immunohistochemical study of the acute and long-term effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the marmoset. 289 93

This study with the rat evaluated the contribution of omega-conotoxin GVIA-(omega-CgTx) and verapamil-sensitive Ca2+ channels in behavioural, antinociceptive and thermoregulatory responses to intracerebroventricular (i.c.v.) injection of [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAMGO), [D-Pen2,D-Pen5]enkephalin (DPDPE) and dynorphin A-(1-17), which are selective agonists for putative mu, delta and kappa-opioid receptors, respectively. The rats treated with omega-CgTx (8-32 pmol i.c.v.) showed transient, dose-dependent shaking behaviour, hyperalgesia and hypothermia which gradually disappeared within 4 h. The behaviour of the rats was normal by 24 h. Histological examination of brain sections showed morphological alterations of neurons in the hippocampus, medial-basal hypothalamus and pyriform cortex. antinociception, catalepsy and thermoregulatory responses elicited by DAMGO (0.4 and 2.0 nmol) were significantly prolonged and potentiated by verapamil (20 pmol i.c.v. 15 min before) or omega-CgTx (8 pmol 24 h before). Antinociception and hypothermia induced by DPDPE were antagonized by verapamil and omega-CgTx, whereas only omega-CgTx prevented the behavioural arousal observed after DPDPE. Similarly, hypothermia induced by dynorphin A-(1-17) (5.0 nmol) and by the kappa-opioid receptor agonist U50,488H (215 nmol) was antagonized by the two Ca2+ channel blockers but only omega-CgTx prevented the barrel rolling and bizarre postures caused by the opioid peptide.
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PMID:Effect of omega-conotoxin and verapamil on antinociceptive, behavioural and thermoregulatory responses to opioids in the rat. 801 57

Antagonism of adenosine A2A receptor function has been proposed as an effective therapy in the treatment of Parkinson's disease. Thus, the study of new adenosine receptor antagonists is of great importance for the potential use of these drugs in clinical practice. The present study evaluated effects of the new preferential adenosine A2A receptor antagonist 2-butyl-9-methyl-8-(2H-1,2,3-triazol-2-yl)-9H-purin-6-ylamine (ST1535) in unilaterally 6-hydroxydopamine lesioned rats. Acute ST1535 dose-dependently potentiated contralateral turning behaviour induced by a threshold dose of l-3,4-dihydroxyphenylalanine (L-DOPA) (3 mg/kg i.p.), a classical test for antiparkinson drug screening. Subchronic (18 days, twice a day) ST1535 (20 mg/kg i.p.)+L-DOPA (3 mg/kg i.p.) did not induce sensitization to turning behaviour or abnormal involuntary movements during the course of treatment, indicating a low dyskinetic potential of the drug. Moreover, while subchronic administration of a fully effective dose of L-DOPA (6 mg/kg i.p.) significantly increased GABA synthesizing enzyme glutamic acid decardoxylase (GAD67), dynorphin and enkephalin mRNA levels in the lesioned striatum, subchronic ST1535 (20 mg/kg i.p.)+L-DOPA (3 mg/kg i.p.) did not modify any of these markers, although it induced a similar number of contralateral rotations at the beginning of treatment. Finally, acute administration of ST1535 (20 mg/kg i.p.) proved capable of reducing jaw tremors in tacrine model of Parkinson's disease tremor. Results showed that ST1535, in association with a low dose of L-DOPA, displayed antiparkinsonian activity similar to that produced by a full dose of L-DOPA without exacerbating abnormal motor side effects. Moreover, in agreement to other well characterized adenosine A2A receptor antagonists, ST1535 features antitremorigenic effects.
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PMID:Characterization of the antiparkinsonian effects of the new adenosine A2A receptor antagonist ST1535: acute and subchronic studies in rats. 1744 98