Alveolar transfer of
prostaglandin E2 (
PGE2) was characterized in isolated perfused guinea pig lungs (n = 19) by measuring radioactivity appearing in the venous effluent during 30 min after intratracheal instillation of [3H]
PGE2, [14C]-
mannitol, and [125I]
iodoantipyrine. Recovery of
lipid-soluble [125I]
iodoantipyrine [91 +/- 3% (SE)] after 30 min was used to estimate total 3H and 14C delivered to the exchanging region of lung at time 0. In seven control lungs, 58 +/- 4% of [14C]
mannitol and 16 +/- 4% of [3H]
PGE2 was retained 10 min after instillation. Neither perfusion with
diphloretin phosphate (10 micrograms/ml; n = 4) nor
hypothermia (5 degrees C; n = 5) significantly affected the amount of [14C]
mannitol retained; however, [3H]
PGE2 remaining in these lungs increased significantly to 36 +/- 4 and 53 +/- 2%, respectively. Addition of unlabeled
PGE2 (200 micrograms) to the instilled
solution (n = 3) increased retention of both [14C]
mannitol (80 +/- 3%) and [3H]
PGE2 (65 +/- 4%). Alveolar transfer of [3H]
PGE2 was calculated as the difference in percent retention of [14C]
mannitol and [3H]
PGE2 and normalized to that of [14C]
mannitol. After 10 min, alveolar transfer of [3H]
PGE2 was 71 +/- 8% in control lungs but was decreased to 26 +/- 7, 10 +/- 5, and 19 +/- 6% by
diphloretin phosphate,
hypothermia, or unlabeled
PGE2, respectively. These data suggest that alveolar clearance of
PGE2 involves a saturable
drug- and temperature-sensitive process.