Pharmacology of the effects of bradykinin, serotonin, and histamine on the release of calcitonin gene-related peptide from C-fiber terminals in the rat trachea.
The effects of inflammatory substances, bradykinin (BK), 5-HT, and histamine (HIS), on the release of calcitonin gene-related peptide (CGRP) from the peripheral terminals of sensory afferents in the rat trachea were examined ex vivo. With intralumenal perfusion, the isolated rat trachea displays low but measurable secretion of CGRP (32 +/- 4.6 fmol/10 min fraction). The addition of BK (10(-6) to 10(-4) M) to the superfusate resulted in an immediate, concentration-dependent increase in the level of CGRP (5-30-fold increase above baseline) in the perfusates, and this effect showed a concentration-dependent tachyphylaxis. [Des-Arg10]-kallidin, a B1 receptor agonist, at concentrations of up to 10(-4) M did not induce any significant increase in CGRP outflow from the rat trachea. HIS at 10(-4) M caused a modest but progressive augmentation in the release of CGRP. 5-HT at 10(-4) M had no effect upon the resting efflux of CGRP, but at a concentration of 10(-6) M significantly enhanced the release of CGRP evoked by capsaicin (10(-6) M). Similar conditioning studies carried out with HIS and BK showed no augmentation. BK-evoked CGRP efflux was significantly inhibited by [D-Arg0, Hyp3, Thi5,8, D-Phe7]-BK (B2 antagonist) and indomethacin. While [Des-Arg9, Leu8]-BK (B1 antagonist) also caused a reduction of BK-induced release, its effect did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Anesthesiology, University of California, San Diego, La Jolla 92093-0818.
Yaksh
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D000818:Animals; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology*; D008297:Male; D009411:Nerve Endings / Q000378:metabolism; D009412:Nerve Fibers / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D014132:Trachea / Q000378:metabolism*
D012702:Serotonin Antagonists; D012701:Serotonin; D006632:Histamine; D015740:Calcitonin Gene-Related Peptide; D001920:Bradykinin