Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.4 (ribonuclease)
 6,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of in utero cocaine exposure on the development of the mRNAs encoding the dopamine transporter (DAT) and the D1, D2 and D5 dopamine receptor subtypes were determined in fetal monkey brains at day 45 and day 60 of gestation. Pregnant monkeys were treated with cocaine 3 mg/kg or saline i.m., four times a day from day 18 of gestation until the pregnancy was terminated at day 45 or day 60. The fetal brains were dissected, and tissue RNA extracted and quantified using ribonuclease protection assay analysis. In day 45 fetal monkeys, dopamine D1 and D2 receptor subtype mRNAs and DAT mRNA were found in low quantities both in control and cocaine-treated subjects. In day 60 fetal monkeys, D1 receptor mRNA levels were highest in the frontal cortex/striatal area, and low to moderate quantities were found in diencephalic and mesencephalic fetal brain regions. Dopamine D2 receptor mRNA levels were highest in the frontal cortex/striatal area, diencephalon and the midbrain, moderate in the brainstem and low in the caudal temporal lobe and surrounding cortical areas. Dopamine D5 receptor mRNA was expressed in low quantities throughout the day 60 fetal monkey brain, whereas DAT mRNA was found in the midbrain only. In utero cocaine exposure caused a significant increase in dopamine D1, D2 and D5 receptor subtype mRNAs in the frontal cortex/striatal area of day 60 fetal monkeys. These results support the hypothesis that dopamine synthesis and release may be reduced in cocaine-treated fetuses, which results in dopamine receptor up-regulation.
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PMID:Effects of in utero cocaine exposure on the expression of mRNAS encoding the dopamine transporter and the D1, D2 and D5 dopamine receptor subtypes in fetal rhesus monkey. 892 87

D2 dopamine receptor antagonism is postulated to be the key to antipsychotic efficacy in the treatment of schizophrenia. Yet the D1 dopamine family of receptors is far more prevalent in the cortical areas of the brain, such as the prefrontal cortex, which have frequently been implicated in schizophrenia. Moreover, the prefrontal cortical D1 sites have recently been shown to be down-regulated by chronic treatment with several commonly used antipsychotic drugs (Lidow and Goldman-Rakic, 1994). To provide further insight into the pharmacological regulation of the D1 class of dopaminergic receptors, we have now used ribonuclease protection assays to examine the regulation of D1 and D5 dopamine receptor mRNAs in the prefrontal cortex and the neostriatum of nonhuman primates after chronic treatment with eight different drugs representing a wide structural and pharmacological spectrum of antipsychotic medications. The medications were administered for 6 months twice daily at doses that fall within the therapeutic range recommended for human patients. The study also included a substituted benzamide, tiapride, which is a D2 antagonist like the eight aforementioned drugs but reportedly lacks antipsychotic activity. Remarkably, all drugs used in this study, including tiapride, down-regulated the levels of both D1 and D5 mRNAs in the prefrontal cortex by 30% to 60% compared with a vehicle control group, whereas mRNAs in the neostriatum were not affected. This observation indicates that a reduction in the levels of prefrontal cortical dopamine receptors of the D1 class may be an obligatory consequence of D2 receptor antagonism and thus may be a pharmacological property of antipsychotic drugs.
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PMID:Down-regulation of the D1 and D5 dopamine receptors in the primate prefrontal cortex by chronic treatment with antipsychotic drugs. 910 49