Canine pulmonary vasoreactivity to serotonin: role of protein
kinase c and tyrosine kinase.
Barman, Scott A., James R. Pauly, and Carlos M. Isales.
Department of Pharmacology and Toxicology, Medical College of
Georgia, Augusta, Georgia 30912
APStracts 3:0399H, 1996.
The role of protein kinase C and protein tyrosine kinase mediated
signal transduction in the canine pulmonary vascular response to
serotonin (5-HT) was determined in the isolated blood perfused dog
lung. Pulmonary vascular resistances and compliances were measured
using vascular occlusion techniques. Serotonin (10-5 M) significantly
increased precapillary resistance by approximately 150% and
postcapillary resistance 2-fold and significantly decreased total
vascular compliance to approximately 50% of control values by
decreasing large vessel compliance and middle compartment compliance.
The 5-HT2 receptor blocker ketanserin (10-7 M), the protein kinase C
inhibitor staurosporine (10-7 M), the voltage dependent calcium
channel blocker verapamil (10-5 M), and the specific protein tyrosine
kinase inhibitors genistein (5 x 10-4 M) and tyrphostin 25 (5 x 10-4
M) completely inhibited the pressor response to serotonin, whereas
the 5-HT1 receptor antagonist (-) pindolol (10-7 M) had no
significant effect on the serotonergic response. These results
indicate that the canine pulmonary vascular response to serotonin
involves activation of 5-HT2 receptors and suggests that this
receptor signal transduction pathway involves protein kinase C and
tyrosine kinase and the activation of voltage dependent calcium
channels.
Received 1 February 1996; accepted in final form 20 August 1996.
APS Manuscript Number H98-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 7 October 1996