ONTOGENIC INCREASE IN PGE(2) AND PGF(2-ALPHA) RECEPTOR DENSITY IN BRAIN MICROVESSELS OF PIGS

1 The hypothesis that the relative vasoconstrictor ineffectiveness of prostaglandin E(2) (PGE(2)) and PGF(2 alpha) on cerebral vessels of newborn pigs might be due to fewer receptors for these prostanoids was tested by comparing receptors for PGE(2) (EP) and PGF(2 alpha) (FP) in cerebral microvessels from newborn and adult pigs. 2 Specific binding of [H-3]-PGE(2) and [H-3]-PGF(2 alpha) to membranes prepared from brain microvessels showed that EF and FP receptor density (B-max) in tissues from newborn animals was less than 50% of that determined in tissues from adults. By contrast, estimates of affinity (K-D) were unchanged. 3 Specifically bound [H-3]-PGE(2) to brain microvessels from both the newborn and adult was displaced by AH 6809 (EP(1)-selective antagonist) by 80-90%, and only by approximately 30-35% by both 11-deoxy PGE(1) (EP(2)/EP(3) agonist) and M&B 28,767 (EP(3) agonist); butaprost (EP(2) agonist) was completely ineffective. 4 PGE(2), 17-phenyl trinor PGE(2) (EP(1) agonist), PGF(2 alpha) and fenprostalene (PGF(2 alpha) analogue) caused significantly less increase in inositol 1,4,5-triphosphate (IP3) in brain microvessels from the newborn than in those from adult pigs. The stimulation of IP3 by PGE(2) and 17-phenyl trinor PGE(2) was almost completely inhibited by the EP(1) antagonist, AH 6809. 5 PGE(2), 11-deoxy PGE(1) and M&B 28,767 produced small reduction of adenosine 3':5'-cyclic monophosphate (cyclic AMP) production in adult vessels but no effect in newborn tissues. 6 The lower density of EP and FP receptors in microvessels of newborn pigs compared to adults may explain the reduced ability of PGE(2) and PGF(2 alpha) to stimulate production of IP3 in tissues from newborn animals. This in turn, may provide an explanation for previous observations demonstrating that these prostanoids elicit contraction of adult cerebral microvessels, but exert minimal effects on these vessels in newborn animals.