MULTIPLE MECHANISMS FOR THE EFFECTS OF CAPSAICIN, BRADYKININ AND NICOTINE ON CGRP RELEASE FROM TRACHEAL AFFERENT NERVES - ROLE OF PROSTAGLANDINS, SYMPATHETIC-NERVES AND MAST-CELLS

Application of capsaicin (CAP), bradykinin (BK) or nicotine (NIC) to i ntraluminally perfused rat tracheas induced an increase in calcitonin gene-related peptide (CGRP) levels in the perfusates. Depletion of sen sory afferent CGRP with systemic CAP pretreatment resulted in a signif icant reduction of CGRP release evoked by CAP, BK or NIC. Chemical des truction of sympathetic nerve fibres by systemic pretreatment with 6-h ydroxydopamine reduced CGRP release evoked by NIC, but did not alter t he release produced by CAP or BK. Elimination of the tracheal mast cel l population by pretreatment with compound 48/80 did not alter the eff ects of CAP, BK or NIC. CGRP release evoked by BK and NIC, but not CAP , was diminished by indomethacin, suggesting that cyclooxygenase produ cts mediate the actions of BK and NIC. Prostaglandins, PGE(1), PGE(2), PGF(2 alpha) and PGI(2), displayed stimulatory effects on CGRP releas e in the trachea. There are evidently multiple mechanisms mediating CG RP release from sensory terminals in rat trachea. It appears that CAP exerts a direct action on sensory nerves, while the effects of BK and NIC are mediated by PG synthesis. Sympathetic activation may be involv ed in NIC, but not BK, induced PG-mediated CGRP release.