ONTOGENY AND PERINATAL REGULATION OF CHOROIDAL PGE₂ AND PGF_2α RECEPTORS IN THE PIG. • 411

PGE₂ and PGF_2α seem to be important in the regulation of choroidal blood flow (ChBF), the main source of O₂ to the retina. In contrast to the adult (A), the newborn (NB) does not exhibit autoregulation of ChBF, which suggests a lack of vasoconstriction. We tested the hypothesis that the type and number of PGE₂ (EP) and PGF_2α (FP) receptors on the choroid (a vascular tissue) of the NB favored less vasoconstriction compared to that of the A, and that high levels of these prostaglandins (PG) in the NB (2-3 fold higher than A) down-regulate EP and FP receptors and their functions. Binding of PGE₂ and PGF_2α, as well as stimulation of inositol 1,4,5 triphosphate (IP₃) and vasomotor reponses to these PG were tested in A, NB (2-3 days old) and NB treated with ibuprofen(Ibu, 30 mg/kg/12 h iv × 24 h [decreased PG to A levels]). Maximum binding (Bmax) of PGE₂ and PGF_2α was 3-4 times lower in NB than A choroid. EP receptors in NB were equally divided between EP₁ and EP₂ subtypes; EP₃ and EP₄ were not detected. In the A≈80% of EP receptors were EP₁; the rest was EP₂ and EP₃ (≈10% each). PGE₂ and butaprost (EP₂ agonist) caused vasodilation of NB choroidal vessels but hardly none of A. PGF_2α, 17-phenyl trinor PGE₂ (EP₁ agonist) and M&B28,767 (EP₃ agonist) caused a 2-3 fold greater constriction of A than NB vessels; effects of EP₁ and FP stimulation were associated with corresponding increases in IP₃. Ibu increased Bmax of PGE₂ and PGF_2α in NB as well as the vasoconstrictor response to EP₁, EP₃ and FP agonists to levels of the A; Ibu virtually abolished dilation to PGE₂ but did not affect response to butaprost. In summary, decreased constriction to EP and FP agonists in the NB is associated with fewer receptors and relatively higher proportion of EP₂ in the NB compared to A. Reduction of PG levels in the NB induces up-regulation of FP, EP₁ and EP₃ (but not EP₂) receptors and their functions to levels of the A. Data suggest that high levels of PG in the perinatal period down-regulate EP₁, EP₃ and FP receptors, which together with increased EP₂ elicit decreased choroidal vasoconstriction to PGF_2α and PGE₂; the findings explain the absence of ChBF autoregulation in the NB leading to increased O₂ delivery to the eye and a risk for retinopathy of prematurity.