Heterogeneity in platelet activating factor (PAF) receptor binding in ovine fetal intrapulmonary arterial (PA) and venous (PV) smooth muscle cells (SMC)

We have reported previously that hypoxia augments PAF receptor (PAF‐r) binding and protein expression in fetal ovine venous smooth muscle cells (SMC‐PV). We compared the effects of hypoxia (pO2 ~30 torr) on PAF‐r binding in SMC from arteries (SMC‐PA) and SMC‐PV. Cells were incubated for 48 h in normoxia (pO2 ~100 torr) or hypoxia. PAF‐r binding was quantified in fmol/106 cells; means ± SEM, n=5. In normoxia, PAF binding in SMC‐PA was 7.7±0.4, which increased to 37.4±2.1 after hypoxia, a 6‐fold increase. In SMC‐PV, the values in normoxia and hypoxia were 19.33 ± 1.08 and 54.1±3.0, 2‐fold increase in hypoxia. Though the increase in binding with hypoxia increased more in SMC‐PA, binding in SMC‐PV was still greater. Hypoxia augmented inositol phosphate (IP3) release by 28%–40% respectively; the levels of IP3 in SMC‐PV during hypoxia were 12‐fold higher than in SMC‐PA. Re‐exposure of hypoxic cells to normoxia for 30 min resulted in decreased binding by 45–60%, suggesting immediate down‐regulation of PAF binding by normoxia. These data show that in fetal ovine SMC, PAF‐r mediated responses are greater in veins than in arteries and that hypoxia significantly augments this response. However, re‐oxygenation immediately reverses this effect of hypoxia. We speculate that this is due to an oxygen tension‐dependent reversibility of auto‐phosphorylation‐dephosphorylation of PAF receptors. Grant NHLBI HL‐077819.