Unique cytosolic ca2+ and adenylyl cyclase responses in phenotypically distinct pulmonary endothelial cells. Stevens, Troy, Brian Fouty, Lisa Hepler, Douglas Richardson, George Brough, Ivan F. McMurtry, and David M. Rodman. Departments of Anesthesiology and Medicine, Cardiovascular Pulmonary Research Laboratory and Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado, U.S.A.
APStracts 3:0142L, 1996.
Pulmonary microvascular endothelium forms a tighter barrier than does pulmonary artery endothelium; the mechanism of this important phenotypic difference is uncertain. We examined two regulators of endothelial permeability, cytosolic calcium ([Ca2+]i) and adenosine 3O5O cyclic monophosphate (cAMP), in microvascular (PMVECs) and pulmonary conduit artery (PAECs) endothelium. Both resting and stimulated [Ca2+]i were lower in PMVECs compared to PAECs (resting [Ca2+]i 94+7 vs. 123+8nM, ATP-stimulated peak 1.04+0.14 vs. 1.98+0.13[mu]M). Sustained Ca2+-transients in response to either ATP or thapsigargin were reduced in PMVECs compared to PAECs (ATP: 199+22 vs. 411+43nM, thapsigargin: 195+13 vs. 527+65nM), suggesting reduced Ca2+ influx in PMVECs. Reduced Ca2+ influx in PMVECs was confirmed by Mn2+-quenching and patch clamp experiments. Messenger RNA for Ca2+ -inhibitable and protein kinase C-stimulated adenylyl cyclases was detected in both cell types. Whereas ATP caused a [Ca2+]i-mediated decrease in cAMP in PAECs, ATP caused a protein kinase C-mediated increase in cAMP in PMVECs. We conclude that PMVECs express a unique phenotype which favors enhanced barrier function through attenuated Ca2+ influx and preservation of cAMP content. 

Received 3 June 1996; accepted in final form 20 August 1996.
APS Manuscript Number L162-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996