Characterization and ontogeny of PGE2 and PGF2 alpha receptors on the retinal vasculature of the pig.
The vasoconstrictor effects of PGE2 and PGF2 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 PGE2) on retinal vessels of the newborn animal. Binding studies using [3H]PGE2 and [3H]PGF2 alpha revealed that PGE2 (EP) and PGF2 alpha (FP) receptor densities in retinal microvessel membrane preparations from newborn animals were approximately 25% of those found in vessels from the adult. The Kd for PGF2 alpha did not differ; however, the Kd for PGE2 was less in newborn than in adult vessels. Competition binding studies using AH 6809 (EP1 antagonist), butaprost (EP2 agonist), M/+B 28,767 (EP3 agonist), and AH 23848B (EP4 antagonist) suggested that the retinal vessels of the newborn contained approximately equal number of EP1 and EP2 receptor subtypes whereas the main receptor subtype in the adult vessels was EP1. In addition, PGE2 and butaprost produced comparable increases in adenosine 3',5'-cyclic monophosphate synthesis in newborn and adult vessels. PGE2, 17-phenyl trinor PGE2 (EP1 agonist) and PGF2 alpha caused a 2.5 to 3-fold greater increase in inositol 1,4,5-triphosphate (IP3) formation in adult than in newborn preparations. It is concluded that fewer PGF2 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 PGF2 alpha on retinal vessels of the newborn than of adult pigs; fewer EP1 receptors (associated with vasoconstriction) and a relatively greater proportion of EP2 receptors (associated with vasodilation) might be responsible for the reduced retinal vasoconstrictor effects of PGE2 in the newborn.
Abran
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Department of Pediatrics, Centre de Recherche de l'Hôpital Sainte-Justine, Québec, Canada.
Li
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Varma
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Chemtob
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D000367:Age Factors; D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001667:Binding, Competitive; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D008833:Microcirculation / Q000187:drug effects; D010120:Oxytocics / Q000494:pharmacology; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism / Q000494:pharmacology*; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D018078:Receptors, Prostaglandin E / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D012160:Retina / Q000737:chemistry*; D013552:Swine / Q000378:metabolism; D014661:Vasoconstriction; D014966:Xanthenes / Q000494:pharmacology; D044004:Xanthones
D010120:Oxytocics; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D011459:Prostaglandins E, Synthetic; D018078:Receptors, Prostaglandin E; D014966:Xanthenes; D044004:Xanthones; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; D000527:Alprostadil; C048491:butaprost; D015232:Dinoprostone