Modification of Modulatory Sites of NMDA Receptor in the Fetal Guinea Pig Brain During Development

Ontogeny of the NMDA receptor and modification of its modulatory sites in the developing fetus brain was determined. MK-801 binding characteristics in the presence of glycine, glutamate, Mg2+ and spermine were determined and used as an index of NMDA receptor modification. Experiments were performed on guinea pig fetuses at 30, 45, 50, 55, and 60 days (term = 63 days) of gestation. The Bmax value increased approximately three-fold from 30 days to 60 days of gestation. The Kd value decreased during the 45-50 day period and then increased toward the end of gestation. The Bmax value reached its maximum level by 55 days of gestation, indicating the presence of a maximum number of NMDA receptors by this age, while the apparent affinity of the receptor showed its peak at 45-50 days of gestation, indicating a potential role for NMDA receptor during the proliferation period of brain development in the guinea pig fetus. The activation of NMDA receptor in the presence of glutamate (10 microM) and glycine (10 microM), as measured by MK-801 binding, was absent at 30 days gestation, with the earliest observation occurring at 35 days gestation. The spermine dependent activation decreased with gestational age. Mg2+ ions increased MK-801 binding in the range of 1-20 microM concentration. Sensitivity to Mg2+ dependent activation increased with the gestational age (from 10 microM Mg2+ at 45 days to 2.5 microM at 55 and 60 days).(ABSTRACT TRUNCATED AT 250 WORDS)