0635 NPY Receptor Agonist Blocks Bradykin/Prostaglandin E2 Evoked Exocytosis from Human Nociceptors
J.L. GIBBS1, Y. SMITH1, K. KEISER1, L.J. CONN, Jr.2, K.M. HARGREAVES1, and K. KEISER1, 1 The University of Texas Health Science Center at San Antonio, USA, 2 University of Texas - San Antonio / Health Science Ctr, USA

Objectives: Neuropeptide Y (NPY) is upregulated in sensory neurons in response to injury and has been implicated in modulating pain. We previously have demonstrated in rats that NPY, via the Y1 receptor, inhibits capsaicin activation of nociceptors and the resulting allodynia. In this study we evaluated whether an agonist at the Y1 receptor is capable of inhibiting a subclass of human nociceptors that are stimulated by the endogenous pain producing substances bradykin (BK) and prostaglandin E2 (PGE2). Methods: The effects of the Y1 agonist [Leu31,Pro34]NPY (LP-NPY) on human PDL nociceptors was determined using isolated human dental roots. Teeth were anesthetized, extracted and the apical 6mm of the roots and attached PDL tissues were resected and the specimens were placed into wells containing buffer with LP-NPY or vehicle for 20 min, then stimulated with BK and PGE2. At the completion of the experiment samples were lysed to release total immunoreactive substance P (iSP). Samples were analyzed for iSP content using RIA. Results: Application of BK and PGE2 (1nM-100 uM) evoked iSP release from isolated human PDL biopsies in a concentration-dependent manner. The application of 100nM LP-NPY completely blocked the release of iSP evoked by 1 uM BK and PGE2 (p<0.005). Conclusions: In addition to inhibiting the capsaicin-sensitive class of nociceptors the NPY system is also active against endogenous activators of pain fibers. These studies give support to the hypothesis that the NPY system is involved in the inhibition of nociceptors and the Y1 receptor is a potential drug target for novel pain therapies. Supported in part by R37DE12888 and F30DE14326.

Seq #71 - Oral Tissues, Pharmacology
11:00 AM-12:15 PM, Thursday, 26 June 2003 Svenska Massan Exhibition Hall B

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