Postnatal changes in N‐methyl‐D‐aspartate receptor binding and stimulation by glutamate and glycine of [3H]‐MK‐801 binding in human temporal cortex

• Published in: British journal of pharmacology 1993-04, Vol.108 (4), p.1143-1149
• Main Authors: Slater, P., McConnell, S.E., D'Souza, S.W., Barson, A.J.
• Format: Article
• Language: English
• Subjects: [3H]‐MK‐801 binding; Adult; Aging - metabolism; Biological and medical sciences; Cerebral Cortex - drug effects; Cerebral Cortex - growth & development; Cerebral Cortex - metabolism; development; Dizocilpine Maleate - metabolism; Female; Glutamates - pharmacology; Glutamic Acid; glycine; Glycine - pharmacology; Humans; In Vitro Techniques; Infant; infant brain; Infant, Newborn; Male; Medical sciences; Miscellaneous; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; N‐Methyl‐d‐aspartate receptor; Pharmacology. Drug treatments; Phencyclidine - analogs & derivatives; Phencyclidine - pharmacology; Proteins - metabolism; Receptors, N-Methyl-D-Aspartate - drug effects; Receptors, N-Methyl-D-Aspartate - metabolism; Stimulation, Chemical; Sudden Infant Death; Temporal Lobe - drug effects; Temporal Lobe - growth & development; Temporal Lobe - metabolism
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1993.tb13518.x

1 Homogenates of human infant and adult temporal cortex were used to measure [3H]‐TCP and [3H]‐MK‐801 binding to the N‐methyl‐d‐aspartate (NMDA)‐coupled ion channel phencyclidine site. 2 Both [3H]‐TCP and [3H]‐MK‐801 binding increased in infant cortex by> 100% between term and 26 weeks suggesting that the numbers of NMDA receptors increase during postnatal brain development. 3 [3H]‐MK‐801 binding was measured under non‐equilibrium conditions in temporal cortex homogenates with the addition of 100 μm of l‐glutamate plus a range of concentrations (0.05 μm−100 μm) of glycine. Glutamate and glycine increased [3H]‐MK‐801 binding by stimulating NMDA receptors and improving [3H]‐MK‐801 access to ion channel binding sites; maximum stimulation in adult and infant temporal cortex was achieved with 100 μm glutamate plus 5 μm glycine; a higher concentration of glycine (50 μm) reduced [3H]‐MK‐801 binding to below maximum. 4 The stimulation by 100 μm glutamate plus 5 μm glycine of [3H]‐MK‐801 binding in infant temporal cortex was affected by postnatal age. For example, although the stimulation of [3H]‐MK‐801 binding in 5–6 week infant cortex (236% of basal) was similar to adult cortex (230% of basal), in samples taken from infants aged 5–6 months glycine (plus glutamate) stimulation of [3H]‐MK‐801 binding (392% of basal) was substantially greater than that measured in adult temporal cortex. 5 The binding of [3H]‐glycine to the glycine modulatory site associated with the NMDA receptor in infant cortex also increased with postnatal age by > 100% between term and 26 weeks. 6 It is concluded that NMDA receptors in infant cortex increase to levels greater than those in adult cortex during postnatal development. The results do not exclude the possibility that the transiently increased NMDA receptor‐ion channel complex in infant cortex shows enhanced responses to agonists and modulators.