T. Stevens et al., CYTOSOLIC CA2-CYCLASE RESPONSES IA PHENOTYPICALLY DISTINCT PULMONARY ENDOTHELIAL-CELLS( AND ADENYLYL), American journal of physiology. Lung cellular and molecular physiology, 16(1), 1997, pp. 51-59
Pulmonary microvascular endothelium forms a tighter barrier than does
pulmonary artery endothelium; the mechanism of this important phenotyp
ic difference is uncertain. We examined two regulators of endothelial
permeability, cytosolic Ca2+ concentration ([Ca2+](i)) and adenosine 3
',5'-cyclic monophosphate (cAMP), in microvascular (PMVEC) and pulmona
ry conduit artery (PAEC) endothelium. Both resting and stimulated [Ca2
+](i) were lower in PMVEC compared with PAEC (resting [Ca2+](i), 94 +/
- 7 vs. 123 +/- 8 nM; ATP-stimulated peak, 1.04 +/- 0.14 vs. 1.98 +/-
0.13 mu M). Sustained Ca2+ transients in response to either ATP or tha
psigargin were reduced in PMVEC compared with PAEC (ATP, 199 +/- 22 vs
. 411 +/- 43 nM; thapsigargin, 195 +/- 13 vs. 527 +/- 65 nM), suggesti
ng reduced Ca2+ influx in PMVEC. Reduced Ca2+ in flux in PMVEC was con
firmed by Mn2+ quenching and patch-clamp experiments. mRNA for Ca2+-in
hibitable and protein kinase C-stimulated adenylyl cyclases was detect
ed in both cell types. Whereas ATP caused a [Ca2+](i)-mediated decreas
e in cAMP in PAEC, ATP caused a protein kinase C-mediated increase in
cAMP in PMVEC. We conclude that PMVEC express a unique phenotype that
favors enhanced barrier function through attenuated Ca2+ influx and pr
eservation of cAMP content.