Journal of Neuroscience, Vol 13, 1947-1953, Copyright © 1993 by Society for Neuroscience
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
XY Hua and TL Yaksh
Department of Anesthesiology, University of California, San Diego, La Jolla 92093-0818.
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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