Gangliosides stimulate synthesis of prostaglandin E2 and prostacyclin in fetal rat brain hemispheres after episodes of global intrauterine ischemia.
The ability of brain preparations from 20-day-old rat fetuses to synthesize prostanoids in vitro before and after interruption of the maternal-fetal blood flow was examined using a radioimmunoassay technique. Synthesis of thromboxane B2 (TxB; the stable thromboxane A2 metabolite) decreased with increasing restriction time; conversely, it was elevated with reperfusion. Synthesis of 6-keto prostaglandin F1 alpha (PGF; the stable prostacyclin metabolite) and prostaglandin E2 (PGE) prostanoids remained unchanged after 20 min restriction and through a 2 hr reperfusion period. Intraperitoneal administration of GM1 (45 mg/kg) into the pregnant rat, 3 hr before restriction, stimulated synthesis of PGE and reduced synthesis of TxB. A prostanoid vasoactive index (PVI), which reflects the relative proportion of the three prostanoids synthesized and asserts the vasoactive potential of the brain tissue, was established. A rise in this value was attained after intrafetal administration into the peritoneal cavity of either GM1, GM3, or isopropyl-GM1 (AGF44) gangliosides, each given at 40 micrograms dose in 5 microliters volume, and N-dichloroacetyl-sphingosine (LIGA20; 15 micrograms/5 microliters) ganglioside analog, 1 hr before restriction. The effect was primarily due to an increase in the capacity of fetal brain tissue to synthesize PGE and, to a lesser extent PGF, vasodilating prostanoids. The N-methyl-D-aspartate (NMDA) receptor-blocker MK801 (6.6 micrograms/2 microliters) and the platelet activating factor (PAF) receptor antagonist BN52021 (0.1 mumol/2 microliters), given by the same route, effectively raised by 60-80% the vasodilating potential of the brain tissue following ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Yavin
E
E
Department of Neurobiology, Weizmann Institute of Science, Rehobot, Israel.
Gil
S
S
Kunievsky
B
B
Harel
S
S
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000098:blood supply*; D005677:G(M1) Ganglioside / Q000494:pharmacology; D005679:G(M3) Ganglioside / Q000494:pharmacology; D005732:Gangliosides / Q000494:pharmacology*; D007511:Ischemia; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D015424:Reperfusion; D013929:Thromboxane B2 / Q000096:biosynthesis
D005679:G(M3) Ganglioside; D005732:Gangliosides; D016194:Receptors, N-Methyl-D-Aspartate; D005677:G(M1) Ganglioside; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D016291:Dizocilpine Maleate; D015232:Dinoprostone