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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Fujita, Ryousuke Ueda, Hiroshi Mizota, Kaori Uchida, Hitoshi Yoshida, Akira |
| Description | Author Affiliation: Mizota K ( Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.) |
| Abstract | 1 Agonistic neurosteroids, including pregnenolone, dehydroepiandrosterone and its sulfate (DHEAS), caused rapid degranulation in measurements of beta-hexosaminidase (beta-HEX) release from a mast cell line, RBL-2H3. This degranulation was blocked by BSA-conjugated progesterone (PROG-BSA) or 17beta-estradiol, both of which are antagonistic neurosteroids. 2 DHEAS-induced beta-HEX release was blocked by U-73122 or xestospongin C, but not by PTX or EGTA. DHEAS-induced beta-HEX release was also abolished by G(q/11)-AS, but not by G(q/11)-MS. Pharmacological analyses revealed that the neurosteroids stimulated a putative membrane receptor through activation of the novel G(q/11) and phospholipase C. 3 While representative endocrine-disrupting chemicals (EDCs) did not show any degranulation or nocifensive actions by themselves, they blocked the DHEAS-induced degranulation. 4 The binding of a PROG-BSA-fluorescein isothiocyanate conjugate (PROG-BSA-FITC) to cells was inhibited by neurosteroids and EDCs. 5 In the algogenic-induced biting and licking responses test, DHEAS caused agonistic nocifensive actions in a dose-dependent manner between 1 and 10 fmol (i.pl.). DHEAS-induced nocifensive actions were abolished by PROG-BSA or nonylphenol. 6 Taken together, these results suggest that a G(q/11)-coupled neurosteroid receptor may regulate the neuroimmunological activity related to sensory stimulation and that some EDCs have antagonistic actions for this receptor. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 4 |
| Volume Number | 145 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2005-06-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | GTP-Binding Protein Alpha Subunits, Gi-Go Metabolism Receptors, Steroid Animals Behavior, Animal Drug Effects Binding, Competitive Cell Line, Tumor Cell Membrane Dehydroepiandrosterone Pharmacology Dehydroepiandrosterone Sulfate Dose-Response Relationship, Drug Estradiol Estrenes Fluorescein-5-isothiocyanate Chemistry Genetics Leukemia, Basophilic, Acute Pathology Macrocyclic Compounds Mast Cells Mice Nociceptors Oligonucleotides, Antisense Oxazoles Pain Chemically Induced Prevention & Control Pertussis Toxin Phenols Phosphodiesterase Inhibitors Pregnenolone Pyrrolidinones Serum Albumin, Bovine Type C Phospholipases Antagonists & Inhibitors Beta-N-Acetylhexosaminidases Secretion Comparative Study Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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