Release of calcitonin gene-related peptide and tachykinins from the rat trachea.
The release of calcitonin gene-related peptide (CGRP), neurokinin A (NKA) and substance P (SP) from intralumenally perfused rat trachea was examined in vitro. In accord with the relative tissue levels of the respective peptides, capsaicin (10(-8) to 10(-5) M) and K+ (120 mM) added to the perfusate resulted in a concentration-dependent increase in the levels of CGRP and NKA, and to a minor extent SP, in the perfusates. Sequential exposure of the trachea to capsaicin revealed a concentration-dependent tachyphylaxis of CGRP release. Thus, 40 min after the application with capsaicin 10(-5) M, a second exposure to capsaicin at the same concentration, or K+ 120 mM, did not evoke CGRP release. In contrast, prior stimulation with K+ 120 mM significantly enhanced the CGRP release induced by a second stimulation with K+ 120 mM or capsaicin 10(-5) M. Capsaicin- and K(+)-induced peptide release was diminished or abolished in the absence of Ca2+. HPLC analysis of CGRP in release materials revealed that there was a single peak which eluted in the same fraction as synthetic rat CGRP. These data demonstrate that CGRP, NKA and SP exist in releasable, capsaicin-sensitive pools in terminals which lie within the proximal lumen of the trachea.
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Anesthesia Research Lab, Department of Anesthesiology, University of California, San Diego, La Jolla 92093-0818.
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D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D015288:Neurokinin A / Q000378:metabolism; D010477:Perfusion; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D013268:Stimulation, Chemical; D013373:Substance P / Q000378:metabolism; D015320:Tachykinins / Q000378:metabolism*; D014132:Trachea / Q000187:drug effects / Q000378:metabolism*
D015320:Tachykinins; D013373:Substance P; D015288:Neurokinin A; D015740:Calcitonin Gene-Related Peptide; D011188:Potassium; D002211:Capsaicin; D002118:Calcium