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Biotech / Medical : ACADIA Pharmaceuticals Inc (ACAD) -- Ignore unavailable to you. Want to Upgrade?

To: scaram(o)uche who wrote (46)	11/10/2004 5:22:34 PM
From: scaram(o)uche	Respond to of 588

Neuroreport. 2004 Sep 15;15(13):2071-5. Stimulation of PAR-2 excites and sensitizes rat cutaneous C-nociceptors to heat. Ding-Pfennigdorff D, Averbeck B, Michaelis M. Aventis Pharma Deutschland GmbH, DG Thrombosis and Degenerative Joint Diseases, Industriepark Hoechst, D-65929 Frankfurt, Germany. Proteinase-activated receptor 2 (PAR-2) is expressed on many nociceptive neurons. Application of PAR-2 agonists has been shown to induce behavioral signs of hyperalgesia. We investigated effects of the rat PAR-2 agonist SLIGRL-NH2 in the isolated rat skin-saphenous nerve preparation. SLIGRL-NH2 (100 microM) excited 20% of all C-fiber nociceptors tested. In addition, C-fiber nociceptors were sensitized to heat after SLIGRL-NH2 application resulting in an increase in response magnitude and a decrease of heat threshold. The PAR-2-inactive control peptide LRGILS-NH2 had no effect. The mechanical sensitivity of C-fibers was not affected by SLIGRL-NH2. PAR-2-mediated excitation and sensitization of primary nociceptors may contribute to PAR-2-mediated hyperalgesia.

To: scaram(o)uche who wrote (46)	12/22/2004 11:29:55 AM
From: tuck	Respond to of 588

[MRG, a Neuron-Specific Gene Family Implicated in Nociception] >>Adaptive Evolution of MRG, a Neuron-Specific Gene Family Implicated in Nociception << genome.org Freebie. >>The MRG gene family (also known as SNSR) . . . " and this begets another search term. Edit: another freebie that may help: "Orphan G protein-coupled receptors MrgA1 and MrgC11 are distinctively activated by RF-amide-related peptides through the Galpha q/11 pathway." pnas.org Cheers, Tuck

To: scaram(o)uche who wrote (46)	12/22/2004 11:49:58 AM
From: tuck	Respond to of 588

"Estrogens effects on the brain: multiple sites and molecular mechanisms." edrv.endojournals.org Reference to ER-beta and pain here. Freebie. Cheers, Tuck

To: scaram(o)uche who wrote (46)	12/22/2004 12:09:11 PM
From: tuck	Respond to of 588

[PAR-2: activation, signalling and function.] >>Biochem Soc Trans. 2003 Dec;31(Pt 6):1191-7. Protease-activated receptor 2: activation, signalling and function. Cottrell GS, Amadesi S, Schmidlin F, Bunnett N. Departments of Surgery and Physiology, University of California-San Francisco, 521 Parnassus Avenue, San Francisco, CA 94143-0660, U.S.A. PARs (protease-activated receptors) are a family of four G-protein-coupled receptors for proteases from the circulation, inflammatory cells and epithelial tissues. This report focuses on PAR(2), which plays an important role in inflammation and pain. Pancreatic (trypsin I and II) and extrapancreatic (trypsin IV) trypsins, mast cell tryptase and coagulation factors VIIa and Xa cleave and activate PAR(2). Proteases cleave PAR(2) to expose a tethered ligand that binds to the cleaved receptor. Despite this irreversible activation, PAR(2) signalling is attenuated by beta-arrestin-mediated desensitization and endocytosis, and by lysosomal targeting and degradation, which requires ubiquitination of PAR(2). beta-Arrestins also act as scaffolds for the assembly of multi-protein signalling complexes that determine the location and function of activated mitogen-activated protein kinases. Observations of PAR(2)-deficient mice support a role for PAR(2) in inflammation, and many of the effects of PAR(2) activators promote inflammation. Inflammation is mediated in part by activation of PAR(2) in the peripheral nervous system, which results in neurogenic inflammation and hyperalgesia.<< Cheers, Tuck