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 intraluminally perfused rat tracheas induced an increase in calcitonin gene-related peptide (CGRP) levels in the perfusates. Depletion of sensory afferent CGRP with systemic CAP pretreatment resulted in a significant reduction of CGRP release evoked by CAP, BK or NIC. Chemical destruction of sympathetic nerve fibres by systemic pretreatment with 6-hydroxydopamine reduced CGRP release evoked by NIC, but did not alter the release produced by CAP or BK. Elimination of the tracheal mast cell population by pretreatment with compound 48/80 did not alter the effects of CAP, BK or NIC. CGRP release evoked by BK and NIC, but not CAP, was diminished by indomethacin, suggesting that cyclooxygenase products mediate the actions of BK and NIC. Prostaglandins, PGE1, PGE2, PGF2 alpha and PGI2, displayed stimulatory effects on CGRP release in the trachea. There are evidently multiple mechanisms mediating CGRP 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 involved in NIC, but not BK, induced PG-mediated CGRP release.
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Department of Anesthesiology, University of California, San Diego, La Jolla 92093.
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D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000502:physiology; D009475:Neurons, Afferent / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D016627:Oxidopamine / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000502:physiology; D014132:Trachea / Q000294:innervation / Q000378:metabolism*; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D011453:Prostaglandins; D003189:p-Methoxy-N-methylphenethylamine; D009538:Nicotine; D016627:Oxidopamine; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D001920:Bradykinin; D007213:Indomethacin