Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The contractile response to three different prostanoids of the isolated human myometrium and the different layers of the uterotubal junction (UTJ) was studied in vitro. The prostaglandin endoperoxide, PGH2, stimulated contractility of both the myometrium and the outer and inner muscle layers of the UTJ, whereas the intermediate layer of the UTJ was inhibited. Thromboxane A2 generated from PGH2 and a thromboxane synthase preparation caused a stimulation of both the myometrium and all three layers of the UTJ. The stimulatory response to TxA2 occurred at concentrations as low as 50-70 pg/ml. The sodium salt of PGi2 was found to relax both the myometrium and all the layers of the UTJ. Intravenous administration of PGI2 in repeated doses between 2-8 microgram induced facial flushing and headache but had little if any effect on in vivo uterine contractility. At least under in vitro conditions, these short-lived prostanoids and/or their metabolites apparently have a specific action on uterine contractility, an action which is manifested at comparatively low concentrations.
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PMID:PGH2, TxA2 and PGI2 have potent and differentiated actions on human uterine contractility. 701 35

GPR109A, a G-protein-coupled receptor, is activated by niacin and butyrate. Upon activation in colonocytes, GPR109A potentiates anti-inflammatory pathways, induces apoptosis, and protects against inflammation-induced colon cancer. In contrast, GPR109A activation in keratinocytes induces flushing by activation of Cox-2-dependent inflammatory signaling, and the receptor expression is upregulated in human epidermoid carcinoma. Thus, depending on the cellular context and tissue, GPR109A functions either as a tumor suppressor or a tumor promoter. However, the expression status and the functional implications of this receptor in the mammary epithelium are not known. Here, we show that GPR109A is expressed in normal mammary tissue and, irrespective of the hormone receptor status, its expression is silenced in human primary breast tumor tissues, breast cancer cell lines, and in tumor tissues of three different murine mammary tumor models. Functional expression of this receptor in human breast cancer cell lines decreases cyclic AMP production, induces apoptosis, and blocks colony formation and mammary tumor growth. Transcriptome analysis revealed that GPR109A activation inhibits genes, which are involved in cell survival and antiapoptotic signaling, in human breast cancer cells. In addition, deletion of Gpr109a in mice increased tumor incidence and triggered early onset of mammary tumorigenesis with increased lung metastasis in MMTV-Neu mouse model of spontaneous breast cancer. These findings suggest that GPR109A is a tumor suppressor in mammary gland and that pharmacologic induction of this gene in tumor tissues followed by its activation with agonists could be an effective therapeutic strategy to treat breast cancer.
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PMID:The niacin/butyrate receptor GPR109A suppresses mammary tumorigenesis by inhibiting cell survival. 2437 Dec 23