Effects of monovalent cations on neostriatal dopamine D2 receptors labeled with [3H]raclopride.
Specific [3H]raclopride binding to dopamine D2 receptors in the rabbit neostriatum was investigated in the presence of the monovalent cations sodium, lithium and potassium. NaCl and LiCl produced concentration-dependent elevations in specific [3H]raclopride binding with sodium inducing approximately 50% more binding than lithium. Inhibition of [3H]raclopride binding by the antagonist (+)-butaclamol was unaffected by the presence of sodium or lithium in the incubation medium. In contrast, the potency of dopamine to compete with [3H]raclopride was decreased by these two ions. This effect was more pronounced in the presence of sodium than lithium and was observed for both the high- and low-affinity states of the D2 receptor. The guanine nucleotide derivative 5'-guanylylimidodiphosphate (Gpp(NH)p) reduced the potency of dopamine to compete with [3H]raclopride binding in both the presence and absence of cations; however, this effect of Gpp(NH)p was a shift of the D2 receptors from a high to a lower affinity state. Saturation binding curves in the presence of sodium or lithium were compared with experiments carried out in the absence of monovalent cations (sucrose) and demonstrated that these ions increased the affinity (judged by the equilibrium dissociation constant Kd) of the neostriatal [3H]raclopride binding sites. While NaCl produced a significantly greater change in the Kd of [3H]raclopride binding as compared to LiCl, no differences were apparent in the maximum binding capacity (Bmax) values determined in the presence of these two cations. In conclusion, the results indicate that [3H]raclopride binding to rabbit neostriatal membranes exhibits a sensitivity to monovalent cations that is consistent with the ionic regulatory properties of the D2 receptor. Moreover, although lithium and sodium influence specific [3H]raclopride binding in a similar manner, there appear to be quantitative differences between these two ions.
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Centre de recherche en sciences neurologiques, Département de physiologie, Université de Montréal, Québec, Canada.
Boulianne
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Molina-Holgado
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Dewar
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D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D006150:Guanine Nucleotides / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D011188:Potassium / Q000494:pharmacology*; D011817:Rabbits; D020891:Raclopride; D011954:Receptors, Dopamine / Q000187:drug effects*; D017448:Receptors, Dopamine D2; D012457:Salicylamides / Q000494:pharmacology*; D012964:Sodium / Q000494:pharmacology*; D014316:Tritium
D006150:Guanine Nucleotides; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D014316:Tritium; D020891:Raclopride; D008094:Lithium; D012964:Sodium; D011188:Potassium