FEWER PGE(2) AND PGF(2-ALPHA) RECEPTORS IN BRAIN SYNAPTOSOMES OF NEWBORN THAN OF ADULT-PIGS

PGE2 and PGF2alpha decrease cerebral metabolism in the adult but incre ase it in the newborn. The present study was done using synaptosomes f rom newborn and adult pigs to find out whether these diverse cerebral effects of prostanoids are a consequence of newborn synaptosomes conta ining fewer or no EP2 receptors for PGE2 (mediating cAMP increase and in turn cerebral metabolism decrease) and PGF2alpha receptors [mediati ng IP3 (inositol 1,4,5-triphosphate) increase and in turn cerebral met abolism decrease]. It was found that maximum binding values (fmol/mg p rotein) of [H-3]PGE2 and [H-3]PGF2alpha 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 a bsent in newborn and adult preparations. Practically all the PGE2 rece ptors on newborn synaptosomes were EP3 subtype, whereas adult brain sy naptosomes contained both EP2 and EP3 subtypes; this was indicated by the ability of M&B 28,767, a specific EP3 receptor agonist, to cause 1 00% displacement of [H-3]PGE2 binding to synaptosomes of the newborn b ut only 51% in the case of the adult. Also, PGE2, 11-deoxy PGE1 (a non selective EP2 and EP3 agonist) and M&B 28,767 (an EP3 agonist) caused comparable decreases in cAMP formation in synaptosomes from the newbor n, whereas in those from the adult, PGE2 and 11-deoxy PGE1 increased a nd M&B 28,767 decreased cAMP production. PGF2alpha markedly increased IP3 synthesis in synaptosomes of the adult but not of the newborn. The se findings suggest that on synaptosomes of the newborn there are fewe r EP3 and PGF2alpha receptors than on those of the adult, and EP2 rece ptors could not be detected in newborn tissues. Because cAMP and IP3 d ecrease cellular metabolism, present data provide an explanation for t he differences in the effects of PGE2 and PGF2alpha on cerebral metabo lic rate between the newborn and the adult.