Journal of Applied Physiology, Vol 66, Issue 2 638-643, Copyright © 1989 by American Physiological Society
PAF-induced contraction of canine trachea mediated by 5-hydroxytryptamine in vivo
T. M. Murphy, N. M. Munoz, J. Moss, J. S. Blake, M. M. Mack and A. R. Leff
Department of Pediatrics, La Rabida Children's Hospital, Chicago, Illinois.
We studied the secretory correlates of tracheal smooth muscle contraction
caused by platelet-activating factor (PAF) in nine mongrel dogs in vivo. In
five dogs, dose-response curves were generated by rapid intra-arterial
injection of 10(-10) to 10(-6) mol PAF into the isolated tracheal
circulation; tracheal contractile response was measured isometrically in
situ. To examine the mechanism by which PAF elicits contraction of canine
trachealis, concentrations of serotonin (5-HT) and histamine were assayed
in the venous effluent as the arteriovenous difference (AVd) in mediator
concentration across the airway for each level of contraction. PAF caused
dose-related active tracheal tension to a maximum of 37.2 +/- 5.4 g/cm
(10(-6) mol PAF). The AVd in 5-HT increased linearly from 0.20 +/- 0.05
(10(-9) mol PAF) to 3.5 +/- 0.3 ng/ml (10(-6) mol PAF) (P less than 0.005).
In contrast, the AVd in histamine was insignificant and did not change with
increasing doses of PAF. A positive correlation was obtained between the
AVd in 5-HT and active tracheal tension (r = 0.92, P less than 0.001);
there was no correlation between AVd in histamine and active tension (r =
-0.16). PAF-induced parasympathetic activation was not mediated by 5-HT;
contraction elicited by exogenous 5-HT was not affected by muscarinic
blockade. We conclude that nonparasympathetically mediated contraction
elicited acutely by PAF in dogs results at least in part from secondary
release of serotonin and is not mediated by histamine.
