Fewer PGE2 and PGF2 alpha receptors in brain synaptosomes of newborn than of adult pigs.
PGE2 and PGF2 alpha decrease cerebral metabolism in the adult but increase it in the newborn. The present study was done using synaptosomes from newborn and adult pigs to find out whether these diverse cerebral effects of prostanoids are a consequence of newborn synaptosomes containing fewer or no EP2 receptors for PGE2 (mediating cAMP increase and in turn cerebral metabolism decrease) and PGF2 alpha receptors [mediating IP3 (inositol 1,4,5-triphosphate) increase and in turn cerebral metabolism decrease]. It was found that maximum binding values (fmol/mg protein) of [3H]PGE2 and [3H]PGF2 alpha were, respectively, only 11.6 +/- 0.8 and 8.6 +/- 1.4 on newborn synaptosomes compared with 41.8 +/- 1.8 and 31.2 +/- 4.8 on adult tissues. EP1 receptors were virtually absent in newborn and adult preparations. Practically all the PGE2 receptors on newborn synaptosomes were EP3 subtype, whereas adult brain synaptosomes contained both EP2 and EP3 subtypes; this was indicated by the ability of M&B 28,767, a specific EP3 receptor agonist, to cause 100% displacement of [3H]PGE2 binding to synaptosomes of the newborn but only 51% in the case of the adult. Also, PGE2, 11-deoxy PGE1 (a nonselective EP2 and EP3 agonist) and M&B 28,767 (an EP3 agonist) caused comparable decreases in cAMP formation in synaptosomes from the newborn, whereas in those from the adult, PGE2 and 11-deoxy PGE1 increased and M&B 28,767 decreased cAMP production. PGF2 alpha markedly increased IP3 synthesis in synaptosomes of the adult but not of the newborn.(ABSTRACT TRUNCATED AT 250 WORDS)
Li
D Y
DY
Department of Pediatrics, Research Centre of Hôpital Sainte-Justine, Montreal, Canada.
Varma
D R
DR
Chatterjee
T K
TK
Fernandez
H
H
Abran
D
D
Chemtob
S
S
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure*; D000242:Cyclic AMP / Q000096:biosynthesis; D015237:Dinoprost / Q000378:metabolism / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007700:Kinetics; D011982:Receptors, Prostaglandin / Q000145:classification / Q000378:metabolism*; D018078:Receptors, Prostaglandin E / Q000145:classification / Q000378:metabolism*; D013552:Swine; D013574:Synaptosomes / Q000378:metabolism / Q000648:ultrastructure*; D014316:Tritium
D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; C034671:prostaglandin F2alpha receptor; D014316:Tritium; D015544:Inositol 1,4,5-Trisphosphate; D015237:Dinoprost; D000242:Cyclic AMP; D015232:Dinoprostone