CHARACTERIZATION AND ONTOGENY OF PGE(2) AND PGF(2-ALPHA) RECEPTORS ONTHE RETINAL VASCULATURE OF THE PIG

The vasoconstrictor effects of PGE(2) and PGF(2 alpha) are less pronou nced on retinal vessels of the newborn than of the adult pig. We teste d the hypothesis that the decreased vasomotor response to these prosta glandins might be due to relatively fewer receptors and/or different r eceptor subtypes (in the case of PGE(2)) on retinal vessels of the new born animal. Binding studies using [H-3]PGE(2) and [H-3]PGF(2 alpha) r evealed that PGE(2) (EP) and PGF(2 alpha) (FP) receptor densities in r etinal microvessel membrane preparations from newborn animals were app roximately 25% of those found in vessels from the adult. The K-d for P GF(2 alpha) did not differ; however, the K-d for PGE(2) was less in ne wborn 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 retina l 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 co mparable increases in adenosine 3',5'-cyclic monophosphate synthesis i n newborn and adult vessels. PGE(2), 17-phenyl trinor PGE(2) (EP(1)ago nist) and PGF(2 alpha) caused a 2.5 to 3-fold greater increase in inos itol1,4,5-triphosphate (IP3) formation in adult than in newborn prepar ations. It is concluded that fewer PGF(2 alpha) receptors and an assoc iated decrease in receptor-coupled IP3 formation in the retinal vessel s 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 grea ter proportion of EP(2) receptors (associated with vasodilation) might be responsible for the reduced retinal vasoconstrictor effects of PGE (2) in the newborn.