Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel class of photoreceptors, the intrinsically photosensitive retinal ganglion cells (ipRGCs), express the photopigment melanopsin and drive non-image-forming responses to light such as circadian photoentrainment, the pupillary light reflex and suppression of nocturnal melatonin production in the pineal. Because dendrites from one subclass of these cells - the M1-type ipRGCs - make presumptive synaptic contacts at sites of dopamine release from dopaminergic amacrine cells, they are prime targets for modulation by dopamine, a neuromodulator implicated in retinal circadian rhythms and light adaptation. In patch-clamp recordings from ipRGCs in intact rat retinas, dopamine attenuated the melanopsin-based photocurrent. We confirmed that this was the result of direct action on ipRGCs by replicating the effect in dissociated ipRGCs that were isolated from influences of other retinal neurons. In these recordings, the D1-family dopamine receptor agonist SKF38393 attenuated the photocurrent, caused a modest depolarization, and reduced the input resistance of ipRGCs. The D2-family agonist quinpirole had no effect on the photocurrent. Single-cell reverse-transcriptase polymerase chain reaction revealed that the majority of ipRGCs tested expressed drd1a, the gene coding for the D1a dopamine receptor. This finding was supported by immunohistochemical localization of D1a receptor protein in melanopsin-expressing ganglion cells. Finally, the adenylate cyclase activator forskolin, applied in combination with the phosphodiesterase inhibitor IBMX (isobutylmethylxanthine), mimicked the effects of SKF38393 on the ipRGC photocurrent, membrane potential and input resistance, consistent with a D1-receptor signaling pathway. These data suggest that dopamine, acting via D1-family receptors, alters the responses of ipRGCs and thus of non-image-forming vision.
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PMID:Dopaminergic modulation of ganglion-cell photoreceptors in rat. 2230 66

The nitric oxide (NO) pathway plays a role in maintaining the function of the prostate. An impairment in the activity of the NO system may have an impact in the manifestation of lower urinary tract symptomatology and benign prostatic hyperplasia. Arginase enzymes (Arg) counteract the generation of NO by depleting the intracellular pool of L-arginine, known to be the substrate of the NO synthases. This study investigated the expression of arginase type I and II in the human prostate. Nondiseased prostate tissue was obtained during pelvic surgeries (prostatectomy, cystoprostatectomy). Tissue sections were exposed to antibodies directed against Arg I and II, cGMP, the phosphodiesterase 5 and nNOS. The expression of mRNA transcripts encoding for Arg I and Arg II was investigated using molecular biology. Reverse transcriptase polymerase chain reaction (RT-PCR) revealed the presence of mRNA encoding for Arg I and II, immunofluorescence specific for Arg I was seen in the stromal smooth musculature, and labelling for PDE5 and cyclic GMP was also observed. Nerve fibres containing nNOS were identified running across the smooth musculature. Immunostainings for Arg II did not yield signals. These findings are in support of the notion that, in the prostate, Arg is involved in the modulation of the activity of the NO system.
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PMID:Arginase enzymes in the human prostate: A molecular biological and immunohistochemical approach. 3148 16

Inflammatory diseases are major health concerns affecting millions of people worldwide. Aspilia africana has been used for centuries by many African communities in the treatment of a wide range of health conditions, including inflammatory diseases, osteoporosis, rheumatic pains, and wounds. Analysis of the phytochemical composition of A. africana indicated that the plant is rich in a broad range of secondary metabolites, including flavonoids, alkaloids, tannins, saponins, terpenoids, sterols, phenolic compounds, and glycosides. This explains the efficacy of the plant in treating inflammation-related diseases, as well as several other health conditions affecting different African communities. The mechanisms of action of the anti-inflammatory phytochemical compounds in A. africana include inhibition of a number of physiological processes involved in the inflammatory process and synthesis or action of proinflammatory enzymes. The phytochemicals enhance anti-inflammatory biological responses such as inhibition of a number of chemical mediators including histamine, prostanoids and kinins, 5-lipoxygenase. and cyclooxygenase and activation of phosphodiesterase and transcriptase. Currently used anti-inflammatory medications are associated with several disadvantages such as drug toxicity and iatrogenic reactions, thereby complicating the treatment process. The adverse effects related to the use of these conventional synthetic drugs have been the driving force behind consideration of natural remedies, and efforts are being made toward the development of anti-inflammatory agents based on natural extracts. A. africana is rich in secondary metabolites, and its use as a traditional medicine for treating inflammatory diseases has been validated through in vitro and in vivo studies. Therefore, the plant could be further explored for potential development of novel anti-inflammatory therapeutics.
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PMID:Ethnopharmacological Potential of Aspilia africana for the Treatment of Inflammatory Diseases. 3273 88


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