Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dopaminergic mechanisms involved in self-inflicting biting behavior (SBB) were investigated in two animal models: monkeys with unilateral ventromedial tegmental (VMT) lesions of the brainstem and rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal dopamine (DA) neurons. The administration of mixed D1/D2 DA agonists to some monkeys with unilateral VMT lesions of the brainstem elicits SBB of the forelimb digits contralateral to the lesion and spasticity of the contralateral hindlimb. This behavior is prevented by pretreatment with the selective D1 antagonist SCH 23390 and with the D1/D2 antagonist fluphenazine. The combined administration of the D1 DA agonist SKF 38393 with the D2 DA agonist quinpirole produces SBB at doses that were ineffective when these drugs were administered individually. The intrastriatal (middle ventrolateral area [MVL]) microinjection of the D1/D2 DA agonist apomorphine (Apo) to rats with unilateral 6-OHDA lesions elicits SBB. This behavior is not prevented by systemic administration of SCH 23390 and partially prevented by the selective D2 antagonist raclopride. However, the combined administration of SCH 23390 and raclopride completely prevents the Apo-induced SBB. Thus, the pharmacological characteristics of the DA agonist-induced SBB in monkeys with unilateral VMT lesions of the brainstem seem to differ from those induced by intrastriatal (MVL area) administration of DA agonists into rats with 6-OHDA lesions of the nigrostriatal DA neurons. The role of DA neuronal systems in the expression of SBB in Lesch-Nyhan syndrome and in some patients with mental retardation, as well as the link between hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency and abnormal dopaminergic function in Lesch-Nyhan syndrome, is discussed.
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PMID:Dopaminergic mechanisms in self-inflicting biting behavior. 269 8

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