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Sodium ion (Na(+)) influences binding of both dopamine agonists and antagonists to D(2) receptors in striatum and retina. Also, Na(+) markedly potentiates the loss of high-affinity agonist binding due to the GTP analogue p[NH]ppG. 2-Amino-6, 7-dihydroxy-1,2,3,4-tetrahydro[5,8-(3)H]naphthalene ([(3)H]ADTN) binds exclusively to an agonist conformation of D(2) receptor in both striatum and retina, distinct from the antagonist conformation labeled by [(3)H]spiroperidol or [(3)H]domperidone in striatum or by [(3)H]spiroperidol in retina. Na(+) is not required for interaction of [(3)H]ADTN or antagonist radioligand sites with the selective D(2) agonist LY-141865, the D(2) antagonist domperidone, or nonselective dopamine agonists or antagonists; however, Na(+) is necessary for high affinity interaction of those radioligand sites with the D(2) antagonists molindone and metoclopramide. With Na(+) present, striatal sites for [(3)H]ADTN, [(3)H]spiroperidol, and [(3)H]domperidone have similar affinities for antagonists but only [(3)H]ADTN sites have high affinity for agonists. Na(+) further decreases the low affinity of dopamine agonists for [(3)H]spiroperidol binding sites. Also, Na(+) enhances [(3)H]spiroperidol and decreases [(3)H]ADTN binding. Na(+) alone causes bound [(3)H]ADTN to dissociate from at least 30% of striatal and 50% of retinal sites, and with Na(+) present [(3)H]ADTN rapidly dissociates from the remaining sites upon addition of p[NH]ppG. It is proposed that D(2) receptors in striatum and retina exist in distinct but interconvertible conformational states, with different properties depending on the presence or absence of Na(+) and of guanine nucleotide.

Sodium ion modulates D 2 receptor characteristics of dopamine agonist and antagonist binding sites in striatum and retina

Sodium ion modulates D ₂ receptor characteristics of dopamine agonist and antagonist binding sites in striatum and retina