Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Benign prostate hyperplasia (BPH) is a common malady affecting elderly men throughout the world, and it is the most common cause of voiding dysfunctions in man. The disease becomes prevalent, as the mean age of the population increases. In BPH the glandular cells and myofibroblasts of periurethral and transition zones proliferate excessively. This excessive growth of tissue mass physically compresses the urethra, leading to urinary obstruction and lower urinary tract symptoms (LUTS). Another major factor that contributes to LUTS in BPH is the increase in smooth muscle tone, a dynamic component. Contraction of the prostate gland is mainly under the control of the autonomic system and is mediated through alpha-adrenoceptors. In addition to alpha1-adrenoceptors, there are many other components that influence growth and contraction of the prostate gland, resulting in the development of BPH and LUTS. The prostate gland is contracted on stimulating 5-HT, endothelin, tachykinin, and muscarinic cholinergic receptors. Growth of the prostate gland is under the control of androgens, endothelin growth factor, vasoactive intestinal peptide, nerve growth factor, and growth hormone. The combination of excessive growth and the tone produced by different components results in LUTS and BPH. alpha1-Adrenoceptor antagonists were successfully used in the treatment of BPH to relieve the LUTS. The high selectivity of alpha1A-adrenoceptor antagonists reflects the uroselectivity. The uroselective compounds like terazosin, doxazosin, tamsulosin, and alfuzosin are in clinical use. Other new potent uroselective compounds, which are analogs of nigulidipine, 5-methyl-urapidil, or naftopidil, are in clinical trials. In addition to alpha-antagonists, antiandrogens (5alpha-reductase inhibitors) and polyherbal formulations are used to treat BPH. The success of BPH treatment lies in the development of new chemical entities which are efficacious as well as more uroselective and hence have least side effects.
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PMID:alpha-Adrenoceptor antagonists in the treatment of benign prostate hyperplasia. 1203 74

Dorsal root ganglia (DRG) which contain glial cells and somas of primary sensory neurons are pivotal for neural transmission between the peripheral and central nervous systems. It is well established that neuropeptides such as substance P and calcitonin gene-related peptide located in DRG neurons control sensory and pain mechanisms. However, contrary to the brain and spinal cord which are extensively investigated, DRG received little attention. Therefore, the current knowledge on DRG may be far to represent their complete neurochemical potential. For instance, until 1997, nothing was known on DRG neurosteroidogenic ability but recently, several investigations have shown that DRG contain various key enzymes synthesizing neuroactive neurosteroids. To provide new advances into DRG neurochemistry, we reviewed and highlighted herein basic and functional evidence showing that neurosteroids are produced in DRG through a neuron-glia crosstalk mechanism. Indeed, key enzymes producing neurosteroids including pregnenolone, progesterone, dihydroprogesterone and estradiol are differentially expressed in DRG cell types. Cytochrome P450side-chain-cleavage is located in DRG neurons and satellite glial cells, 3beta-hydroxysteroid dehydrogenase is expressed in Schwann cells and neurons, 5alpha-reductase is localized in satellite glial and Schwann cells (not in neurons) while aromatase is present in neurons but not in glia. Recent studies also revealed that DRG neurosteroidogenesis is a physiologically relevant process selectively regulated under pathological conditions. Acting through paracrine and autocrine mechanisms, endogenous neurosteroids modulate DRG sensory functions and protect DRG neurons against death. The paper suggests that DRG neurosteroidogenic components may be targeted for the development of therapies against peripheral nerve injury-induced afferent noxious stimulations.
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PMID:Progress in dorsal root ganglion neurosteroidogenic activity: basic evidence and pathophysiological correlation. 2043 98