Effects of sodium, lithium, and magnesium on in vitro binding of [3H]SCH23390 in rat neostriatum and cerebral cortex.
The effects of sodium, lithium, and magnesium on the in vitro binding properties of the D1 antagonist [3H]SCH23390 were examined with membrane preparations from rat neostriatum (CPU; caudate-putamen) and cerebral cortex (CTX). The saturation binding isotherms for both tissues performed in the presence of 120 mM of either Na+ or Li+ revealed an increase in the affinity, as compared to that observed when the incubation buffer was composed of Tris-Cl 50 mM with MgCl2 1 mM alone. For the CPU there were no changes in the maximum binding capacity (Bmax) in the different buffers used. In the case of the CTX, there was a loss of [3H]SCH23390 binding sites when either Na+ or Li+ 120 mM were added to the incubations, suggesting a lack of selectivity of this ligand in the absence of group IA cations. The agonist state of the [3H]SCH23390 binding site was studied in competition experiments with dopamine. The highest agonist affinity was obtained in 50 mM Tris-Cl buffer with 1 mM MgCl2 while the addition of 120 mM of either Na+ or Li+ caused a 3- to 5-fold decrease in the potency of dopamine to compete with specific [3H]SCH23390 binding in both CPU and CTX. The presence of magnesium was essential for the competition experiments; i.e.: a concentration of 1 mM MgCl2 was optimum to obtain dopamine antagonism of ligand binding, while increasing Mg2+ to 2 or 5 mM did not appear to further improve the inhibitions. The results support both agonist and antagonist affinity shifts for the dopamine D1 receptor labeled with [3H]SCH23390.(ABSTRACT TRUNCATED AT 250 WORDS)
Gottberg
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Departamento de Fisiologia, Facultad de Medicina, Universidad Central de Venezuela, Caracas.
Diop
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L
Montreuil
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B
Reader
T A
TA
D000818:Animals; D001552:Benzazepines / Q000378:metabolism*; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D018492:Dopamine Antagonists; D066298:In Vitro Techniques; D008094:Lithium / Q000494:pharmacology*; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D012964:Sodium / Q000494:pharmacology*
D001552:Benzazepines; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D008094:Lithium; D012964:Sodium; D008274:Magnesium