The objective of the proposed studies is to achieve a better understanding of molecular mechanisms of nociception and analgesia. AN analgesia and anesthesia. In particular, the proposed studies will examine the interaction of the substance P receptor, a key protein in nociception, with its transmitter, with its downstream signalling machinery (G-protein), and with local anesthetics.
The specific aims are: 1) To determine which regions of the substance P receptors interact with which regions of its agonist by incorporation of photolabile substance P into the receptor protein and determining the site of insertion 2) To examine the role of particular regions of the receptor in interacting with its G-protein by perturbing the intact and disassembled system with synthetic peptides and antibodies directed to discrete receptor regions. 3) To characterize the interaction of local anesthetic with the receptor by examining the inhibition of the receptor by these drugs under differing conditions.
