Regulation of cerebrovascular prostaglandin E2 (PGE2) and PGF2 alpha receptors and their functions during development.
The density of PGF2 alpha (FP) and PGE2 (EP) receptors on the cerebral microvasculature of the newborn is less than on that of the adult animal. High levels of prostaglandins in the newborn brain could be responsible for down-regulation of FP and EP receptors and their functions in the cerebral microvasculature. Cerebrovascular FP and EP receptor density, receptor-coupled second messenger production and cerebral vasoconstrictor responses to PGF2 alpha and PGE2 were studied in newborn pigs (1 to 2 days old) treated intravenously with ibuprofen (40 mg/kg every 6 hours for 48 hours) or saline, and compared with adults. Ibuprofen treatment in the newborn increased brain microvascular FP and EP receptor densities to levels found in that of adult pigs. Likewise brain microvessel inositol 1,4,5-triphosphate production in response to PGF2 alpha, fenprostalene (PGF2 alpha analog), PGE2, 17-phenyl trinor PGE2 (EP1 receptor subtype agonist) and M&B 28,767 (EP3 agonist) was greater in ibuprofen-treated newborn pigs; the latter was associated with increased vasoconstriction to these agents to levels comparable with those of adults. Steady-state levels of FP receptor mRNA in cerebral microvas-culature did not differ between saline-treated newborn, and ibuprofen-treated newborn and adult pigs. It is concluded that the low FP and EP receptor densities and receptor-coupled functions on newborn brain microvessels seem to be secondary to high levels of brain prostaglandins; the changes in receptor levels do not seem to be related to steady-state levels of receptor mRNA in brain microvessels.
Chemtob
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Department of Pediatrics, Höpital Sainte-Justine, Montreal, Canada.
Li
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Abran
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Peri
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Varma
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D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000098:blood supply*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015237:Dinoprost / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis*; D007052:Ibuprofen / Q000494:pharmacology; D008833:Microcirculation / Q000254:growth & development / Q000502:physiology; D011982:Receptors, Prostaglandin / Q000378:metabolism / Q000502:physiology*; D018078:Receptors, Prostaglandin E / Q000378:metabolism / Q000502:physiology*; D015290:Second Messenger Systems / Q000502:physiology; D013552:Swine; D014661:Vasoconstriction / Q000502:physiology
D016861:Cyclooxygenase Inhibitors; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; C034671:prostaglandin F2alpha receptor; D015237:Dinoprost; D015232:Dinoprostone; D007052:Ibuprofen