NEUROSTEROID MODULATION OF THE BENZODIAZEPINE RECEPTOR IN DEVELOPING CHICK OPTIC LOBE

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• 作者：PIGNATARO ; LEONARDO ; GRAVIELLE ; MARÍ ; A CLARA ; DE PLAZAS ; SARA FISZER
• 刊名：Neurochemistry International
• 出版年：1996
• 出版时间：October, 1996
• 年：1996
• 卷：29
• 期：4
• 页码：405-410
• 全文大小：428 K

文摘

The modulation of [³H]flunitrazepam binding by 3α-hydroxy-5α-dihydroprogesterone (3α-OH-DHP) and 3α,5α-tetrahydrodeoxicorticosterone (3α-THDOC) was investigated in synaptic membranes isolated from chick optic lobe at three developmental stages, in order to evaluate the role of neurosteroids in central nervous system functional maturation. It was demonstrated that both steroids modulate [³H]flunitrazepam binding in a concentration-dependent manner at embryonic day 14, hatching and adult stage, producing maximal [³H]flunitrazepam binding enhancement at early stages of development and declining thereafter. EC₅₀ values for 3α-OH-DHP were lower than for 3α-THDOC at all stages examined. On the other hand, E_max values were higher with 3α-OH-DHP than with 3α-THDOC. Scatchard analysis performed at embryonic day 14, hatching and adult stage showed that dissociation constants (K_d) were of 22.23±0.15, 18.38±1.15 and 19.86±0.62 nM, and maximal number of binding sites (B_max) were 1.95±0.15, 3.13±0.21 and 2.25±0.13 pmol/mg protein, respectively. By adding 4 μM of either 3α-OH-DHP or 3α-THDOC, K_d values decreased significantly to 10.65±0.62, 9.71±0.85 and 13.25±0.74 nM or 9.54±0.65, 11.20±1.27 and 12.96±1.38 nM, at the above mentioned stages, respectively. Thus, either drug at the given concentration increased the affinity of benzodiazepine receptor sites for [³H]flunitrazepam, while the density of receptor sites remained unchanged. Our results suggest that these steroids display a positive allosteric modulation of benzodiazepine receptor sites which is inversely related to age.