Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00492 (hypoxanthine-guanine phosphoribosyltransferase)
 2,385 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Monkeys with surgical unilateral ventromedial tegmental lesions of the brain stem served as models for investigating abnormalities in Parkinson's disease and Lesch-Nyhan syndrome. 2. The animals exhibited some neurological deficits which are similar to those observed in Parkinson's disease or Lesch-Nyhan syndrome. 3. In monkeys with unilateral ventrolateral tegmental lesions, the levels of dopamine and the activities of catecholamine-synthesizing enzymes were reduced on the lesion side of the striatum, and hypokinesia and tremor developed on the contralateral extremities. 4. Dopa or dopamine agonists relieve tremor and evoke abnormal involuntary movements which are similar to the responses observed in patients with Parkinson's disease. 5. The antitremor effect of Dopa is potentiated by catechol-O-methyltransferase inhibition, suggesting a therapeutic potential for these types of agents. 6. Evidence was obtained that stimulation of D2 dopamine receptors by selective dopamine agonists exerts antitremor activity and evokes abnormal involuntary movements. 7. Combined administration of D1 and D2 dopamine agonists seems to enhance the antitremor activity. 8. Partial dopamine agonists exert antitremor activity and produce less severe abnormal involuntary movements than full dopamine agonists. 9. In a group of monkeys with unilateral ventromedial tegmental lesions of the brain stem the administration of mixed D1/D2 dopamine agonists results in the occurrence of self-biting behavior of the forelimb digits and spasticity of the hindlimbs and these symptoms are similar to those observed in patients with Lesch-Nyhan syndrome. 10. The self-biting behavior seems to be associated with the stimulation of central D1 dopamine receptors and therefore the possible involvement of dopamine neuronal abnormalities in Lesch-Nyhan syndrome deserves further investigation.
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PMID:Monkeys with unilateral ventromedial tegmental lesions of the brain stem: models for Parkinson's disease and Lesch-Nyhan syndrome. 250 25

We have investigated the effects of various dopamine (DA) agonists on induction of abnormal involuntary movements (AIM) in a group of monkeys which had denervated nigro-striatal DA neurons for 10-14 years rendered by a unilateral surgical ventromedial tegmental (VMT) lesion of the brainstem. The surgical lesions were placed when the monkeys were 2-4 years old. The administration of mixed DA agonists, such as L-DOPA, apomorphine (Apo) and abeorphine 201-678, elicit a self-mutilative biting behavior (SMB) of the forelimb digits contralateral to the lesion, and spasticity of the contralateral hindlimb. These dysfunctions resemble, in some aspects, the neurological disturbances associated with Lesch-Nyhan syndrome. The SMB behavior was elicited by mixed DA agonists which predominantly stimulate D1, but not D2 DA receptors, and was prevented or abolished by the D1 DA antagonist SCH 23390 or by the D1 and D2 DA antagonist fluphenazine (Flu), but not by the D2 antagonist (+/-)sulpiride. These results suggest that DA agonist-induced SMB behavior is mediated by D1 and/or by both D1 and D2 DA receptor pathways. To study the relationships between HPRT, the defective enzyme in Lesch-Nyhan syndrome, and the DA neuronal systems, we have measured the effects of nigro-striatal DA degeneration and intrastriatal neuronal degeneration on HPRT activity. The unilateral 6-OHDA-induced nigro-striatal DA degeneration does not significantly alter the HPRT activity on the lesioned side of the striatum, while the quinolinic acid-induced intrastriatal neuronal degeneration significantly reduces the enzyme activity. These results suggest that HPRT is localized on intrastriatal neurons which are also known to contain DA receptors. It is postulated that HPRT deficiency in Lesch-Nyhan syndrome results in abnormal guanine nucleotide metabolism which may affect the regulation of DA receptors.
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PMID:Dopamine agonist induced self-mutilative biting behavior in monkeys with unilateral ventromedial tegmental lesions of the brainstem: possible pharmacological model for Lesch-Nyhan syndrome. 293 64

A variety of inheritable metabolic disorders produce movement disorders. A lists of conditions associated with tremor, athetosis, chorea, dystonia and myoclonus are presented as a guide for the differential diagnosis of such abnormal involuntary movements. The list includes aminoacidopathies, lipidoses, mucopolysaccharidoses, mucolipidoses, organic acidemias, mitochondrial cytopathies and disorders of carbohydrate, purine, and metal metabolism. Clinical, pathological and biochemical features of movement disorders of three typical examples, Wilson's disease, Lesch-Nyhan syndrome and glutaric acidemia type 1, are described.
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PMID:[Movement disorders in miscellaneous disorders--inherited metabolic diseases]. 827 72