Ontogenic increase in PGE2 and PGF2 alpha receptor density in brain microvessels of pigs.
1. The hypothesis that the relative vasoconstrictor ineffectiveness of prostaglandin E2 (PGE2) and PGF2 alpha on cerebral vessels of newborn pigs might be due to fewer receptors for these prostanoids was tested by comparing receptors for PGE2 (EP) and PGF2 alpha (FP) in cerebral microvessels from newborn and adult pigs. 2. Specific binding of [3H]-PGE2 and [3H]-PGF2 alpha to membranes prepared from brain microvessels showed that EP and FP receptor density (Bmax) in tissues from newborn animals was less than 50% of that determined in tissues from adults. By contrast, estimates of affinity (KD) were unchanged. 3. Specifically bound [3H]-PGE2 to brain microvessels from both the newborn and adult was displaced by AH 6809 (EP1-selective antagonist) by 80-90%, and only by approximately 30-35% by both 11-deoxy PGE1 (EP2/EP3 agonist) and M&B 28,767 (EP3 agonist); butaprost (EP2 agonist) was completely ineffective. 4. PGE2, 17-phenyl trinor PGE2 (EP1 agonist), PGF2 alpha and fenprostalene (PGF2 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 PGE2 and 17-phenyl trinor PGE2 was almost completely inhibited by the EP1 antagonist, AH 6809. 5. PGE2, 11-deoxy PGE1 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 PGE2 and PGF2 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.
Department of Pharmacology & Therapeutics, McGill University, Montreal, Canada.
D Y
DY
Li
D R
DR
Varma
S
S
Chemtob
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development*; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D007293:Inosine Triphosphate / Q000096:biosynthesis; D007700:Kinetics; D008024:Ligands; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000378:metabolism*; D018078:Receptors, Prostaglandin E / Q000187:drug effects / Q000378:metabolism*; D013552:Swine
D008024:Ligands; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D007293:Inosine Triphosphate; D015237:Dinoprost; D000242:Cyclic AMP; D015232:Dinoprostone