Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Quinolinic acid (QA) is an endogenous excitotoxin present in mammalian brain that reproduces many of the histologic and neurochemical features of Huntington's disease (HD). In the present study we have examined the ability of a variety of systemically administered compounds to modify striatal QA neurotoxicity. Lesions were assessed by measurements of the intrinsic striatal neurotransmitters substance P, somatostatin, neuropeptide Y, and GABA. Histologic examination was performed with Nissl stains. The antioxidants ascorbic acid, beta-carotene, and alpha-tocopherol administered s.c. for 3 d prior to striatal QA lesions had no significant effect. Other drugs were administered i.p. 1/2 hr prior to QA striatal lesions. The following were ineffective in blocking QA excitotoxicity: allopurinol, 50 and 100 mg/kg; ketamine, 75 mg/kg; nimodipine, 2.4, and 10 mg/kg; baclofen, 10 mg/kg; 2-amino-5-phosphonovalerate, 50 mg/kg; and 2-amino-7-phosphonoheptanoate, 50 mg/kg. Oral taurine administration for 4 weeks resulted in significantly increased levels of brain taurine but had no significant effect in blocking QA neurotoxicity. Systemic administration of the noncompetitive N-methyl-D-aspartate (NMDA) antagonist MK-801 resulted in a dose-responsive protection against QA toxicity, with complete block at a dose of 4 mg/kg. If the pathogenesis of HD involves QA or another excitotoxin acting at the NMDA receptor, it is possible that MK-801 could retard the degenerative process.
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PMID:Systemic approaches to modifying quinolinic acid striatal lesions in rats. 246 37

Quinolinic acid (QUIN) is an endogenous excitatory amino acid, which is elevated in brain tissues or cerebrospinal fluid (CSF) in several acute and chronic inflammatory central nervous system (CNS) diseases. The functional significance of this elevation is unknown but speculations of excitotoxicity have been raised. We have begun to address the pathologic consequences of elevated CSF QUIN by studying the effects of intracerebroventricular (i.cv) administration of QUIN on regional choline acetyltransferase (ChAT) activity, somatostatin content and glucose metabolism in the rat brain. QUIN (12 and 60 nmol) i.cv administration once a day for 7 days (total dose; 84 and 420 nmol, respectively) had minimal effect on somatostatin content and no effect on ChAT activity. In contrast, following continuous i.cv infusion of QUIN for 14 days using an osmotic minipump (480 nmol), ChAT activity dropped in the hippocampus and the striatum and somatostatin content was reduced in the frontal cortex, hippocampus, striatum and amygdala. Moreover, following the QUIN infusion, glucose utilization decreased in the basal nucleus of Meynert, frontal cortex, and portions of the basal ganglia and the limbic system. These results indicate that subchronic i.cv infusion of QUIN to rats results in selective regional neurochemical and metabolic changes distributed throughout the CNS. These results suggest target brain areas and transmitter systems which may be associated with neurologic syndromes characterized by elevated CSF QUIN levels.
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PMID:Neurochemical and metabolic consequences of elevated cerebrospinal fluid quinolinic acid concentrations in rat brain. 952 21