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Cyclic Nucleotides Down‐Regulate Platelet Activating Factor Receptor (PAFr) Protein Expression in Ovine Fetal Pulmonary Arterial Smooth Muscle Cells (SMC‐PA)
Author(s) -
McPeak Amy M,
Douglass Stephen M.,
Ibe Basil O.,
Raj J. Usha
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb113-b
Subject(s) - hypoxia (environmental) , receptor , platelet activating factor receptor , medicine , hypoxic pulmonary vasoconstriction , endocrinology , nucleotide , downregulation and upregulation , vascular smooth muscle , chemistry , biology , vasoconstriction , biochemistry , smooth muscle , antagonist , organic chemistry , oxygen , gene
The cyclic nucleotides, cGMP and cAMP, elicit smooth muscle relaxation via their endogenous receptors PKG and PKA respectively. We recently showed that cGMP and cAMP modulate PAFr‐mediated cell signaling and that PAF inhibits PKG and PKA expression in ovine fetal pulmonary venous smooth muscle (Ibe et al, JPET 320:, 2007). To further delineate the interactions between the PAF‐PAFr pathway and the cyclic nucleotides, we studied the effects of cGMP and cAMP on PAFr protein expression in SMC‐PA. Ovine fetal SMC‐PA were incubated for 3 h with 0.1% BSA buffer alone or buffer containing 10μM cGMP or cAMP in normoxia (5% CO 2 in air, pO 2 ~100 torr) or hypoxia (2% O 2 , 5% CO 2 , pO 2 ~30–40 torr). Proteins were prepared from treated and untreated cells and subjected to Western blotting. During normoxia, exogenous cGMP decreased PAFr protein expression by 10%, whereas cAMP decreased it by 80%. During hypoxia, cGMP and cAMP decreased PAFr expression by 73% and 90% respectively. Both cyclic nucleotides attenuated PAFr protein expression, more so in hypoxia, when PAFr expression is usually high. These data suggest that the normally high levels of cyclic nucleotides in the normoxic newborn pulmonary circulation assist in downregulation of PAFr‐mediated responses postnatally and that under hypoxic conditions, increasing the levels of cyclic nucleotides will combat PAF‐mediated vasoconstriction. Supported by Grant NHLBI#077819.