Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, a species-dependent distribution of melatonin binding sites have been found in lamina I-V and lamina X of the spinal cord. In order to learn more about the function of spinal melatonin receptors, we investigated (i) the gene expression for melatonin receptor subtypes in lumbar and thoracal spinal cord tissue by means of the reverse-transcriptase polymerase chain reaction (RT-PCR) technique, and (ii) the electrophysiological and pharmacological properties of melatonin receptors heterologously expressed in Xenopus oocytes after injection of spinal cord mRNA by means of the voltage clamp technique. Because ample evidence indicates an antinociceptive effect of melatonin, (iii) the role of spinal melatonin receptors for maintaining mechanical and thermal hyperalgesia was studied in a rat model for postoperative pain. The RT-PCR data revealed that transcripts for MT1 and MT2 melatonin receptors are present in the dorsal and ventral horn of lumbar and thoracal spinal cord tissue. Injection of mRNA from lumbar spinal cord tissue into Xenopus oocytes led to the functional reconstitution of melatonin receptors which activate calcium-dependent chloride inward currents. Melatonin responses were abolished by simultaneous administration of the antagonists, 2-phenylmelatonin and luzindole and were unaffected by the MT2 antagonist 4-phenyl-2-propionamidotetralin. Intrathecal administration of different melatonin doses (10-100 nmol) did not inhibit mechanical or thermal hyperalgesia. However, intrathecal application of a low dose of morphine together with melatonin caused a brief antinociceptive effect suggesting an enhanced morphine analgesia by melatonin. In conclusion, the present study demonstrated for the first time the presence of transcripts of MT1 and MT2 receptors located in the dorsal and ventral horn of the spinal cord. Furthermore, spinal melatonin enhanced the antinociceptive effect of morphine indicating that melatonin acts as a neuromodulator in the spinal cord.
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PMID:Gene expression and functional characterization of melatonin receptors in the spinal cord of the rat: implications for pain modulation. 1282 10

Our previous study showed that YGGFMKKKFMRFamide (YFa), a chimeric peptide of Met-enkephalin, and Phe-Met-Arg-Phe-NH2 induced naloxone-reversible antinociception and attenuated the development of tolerance to morphine analgesia. In continuation, the present study investigated which specific opioid receptors-mu, delta or kappa-mediate the observed YFa antinociception pharmacologically using specific antagonists and whether chronic administration of YFa at 26.01 micromol/kg per day induces tolerance and its effect on the expression of mu and kappa opioid receptors from day 4 to day 6, with endomorphine-1 (EM-1) and saline taken as positive and negative controls, respectively. Quantitative differential expression analysis was carried out by real-time reverse-transcriptase polymerase chain reaction, and the corresponding changes in protein levels were assessed by Western blot. A pharmacological investigation revealed that nor-binaltorphimine, a specific kappa opioid receptor-1 (KOR1) antagonist, completely antagonized the antinociception induced by 39.01 micromol/kg of YFa. Importantly, its chronic intraperitoneal administration did not result in significant tolerance over 6 days, whereas EM-1 induced significant tolerance after day 4. Differential expression analysis revealed that EM-1 caused up-regulation of mu opioid receptor-1 on day 4, followed by down-regulation on later days. Interestingly, YFa treatment caused a decrease on day 4, followed by an increase in the expression of KOR1 from day 5 onward. In conclusion, YFa induces kappa-specific antinociception, with no development of tolerance during 6 days of chronic treatment, which further articulates new directions for improved designing of peptide-based analgesics that may be devoid of adverse effects like tolerance.
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PMID:YFa, a chimeric opioid peptide, induces kappa-specific antinociception with no tolerance development during 6 days of chronic treatment. 1818 21