NDLI: Sodium ion modulates $D_{2}$ receptor characteristics of dopamine agonist and antagonist binding sites in striatum and retina

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Sodium ion modulates $D_{2}$ receptor characteristics of dopamine agonist and antagonist binding sites in striatum and retina

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Sodium ion modulates $D_{2}$ receptor characteristics of dopamine agonist and antagonist binding sites in striatum and retina

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Klein, P. N. Makman, M. H. Dvorkin, B.
Abstract	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.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	13
Volume Number	79
Language	English
Publisher	National Academy of Sciences
Publisher Date	1982-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Corpus Striatum Metabolism Receptors, Dopamine Retina Sodium Pharmacology Animals Binding, Competitive Domperidone Kinetics Receptors, Dopamine D2 Spiperone Tetrahydronaphthalenes Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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