Characterization and ontogeny of PGE(2) and PGF(2 alpha) receptors on the retinal vasculature of the pig

The vasoconstrictor effects of PGE(2) and PGF(2 alpha) are less pronounced on retinal vessels of the newborn than of the adult pig. We tested the hypothesis that the decreased vasomotor response to these prostaglandins might be due to relatively fewer receptors and/or different receptor subtypes (in the case of PGE(2)) on retinal vessels of the newborn animal. Binding studies using [H-3]PGE(2) and [H-3]PGF(2 alpha) revealed that PGE(2) (EP) and PGF(2 alpha) (FP) receptor densities in retinal microvessel membrane preparations from newborn animals were approximately 25% of those found in vessels from the adult. The K-d for PGF(2 alpha) did not differ; however, the K-d for PGE(2) was less in newborn than in adult vessels. Competition binding studies using AH 6809 (EP(1) antagonist), butaprost (EP(2) agonist), M (sic) B 28,767 (EP(3) agonist), and AH 23848B (EP(4) antagonist) suggested that the retinal vessels of the newborn contained approximately equal number of EP(1) and EP(2) receptor subtypes whereas the main receptor subtype in the adult vessels was EP(1). In addition, PGE(2) and butaprost produced comparable increases in adenosine 3',5'-cyclic monophosphate synthesis in newborn and adult vessels. PGE(2), 17-phenyl trinor PGE(2) (EP(1)agonist) and PGF(2 alpha) caused a 2.5 to 3-fold greater increase in inositol1,4,5-triphosphate (IP3) formation in adult than in newborn preparations. It is concluded that fewer PGF(2 alpha) receptors and an associated decrease in receptor-coupled IP3 formation in the retinal vessels of the newborn could lead to weaker vasoconstrictor effects of PGF(2 alpha) on retinal vessels of the newborn than of adult pigs; fewer EP(1) receptors (associated with vasoconstriction) and a relatively greater proportion of EP(2) receptors (associated with vasodilation) might be responsible for the reduced retinal vasoconstrictor effects of PGE(2) in the newborn.