Pharmacology of calcitonin gene related peptide release from sensory terminals in the rat trachea.
In an intraluminally perfused rat trachea model, we have observed the following. (i) Capsaicin evoked a concentration-dependent calcitonin gene related peptide (CGRP) release from the trachea. Its effects were mimicked by the capsaicin analogue resiniferatoxin and blocked by capsazepine, a competitive antagonist of capsaicin. Capsazepine did not attenuate the peptide release evoked by bradykinin, nicotine, or prostaglandin E2. (ii) Elevation of extracellular H+ resulted in a proton concentration dependent increase in CGRP release, but this was not inhibited by capsazepine. (iii) Indomethacin treatment did not alter capsaicin- or proton-induced CGRP release; in contrast bradykinin- and nicotine-induced release were significantly reduced. (iv) Chemical destruction of sympathetic nerve fibers by systemic pretreatment with 6-hydroxydopamine reduced CGRP release evoked by nicotine, but the release produced by capsaicin or bradykinin remained unchanged. These results suggest that the effect of capsaicin on tracheal CGRP release occurs via activation of specific capsaicin receptors on primary sensory C-fibers, while protons act at a different site from that acted upon by capsaicin in the trachea. Cyclooxygenase products are likely involved in the effects of bradykinin and nicotine, but not those of capsaicin and protons. Sympathetic activation may mediate nicotine-, but not bradykinin- or capsaicin-induced CGRP release. These observations indicate that factors present in the extravascular--extracellular melieu of the trachea can evoke the release of CGRP from sensory C-fibers and that there are multiple mechanisms whereby these agents may interact with the afferent terminals.
Hua
X Y
XY
Department of Anesthesiology, University of California, San Diego, La Jolla 92093-0818, USA.
Wong
S
S
Jinno
S
S
Yaksh
T L
TL
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009412:Nerve Fibers / Q000378:metabolism*; D016627:Oxidopamine / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000502:physiology; D014132:Trachea / Q000294:innervation*
D011453:Prostaglandins; D016627:Oxidopamine; D015740:Calcitonin Gene-Related Peptide; C071423:capsazepine; D002211:Capsaicin; D007213:Indomethacin