Interaction of permanently uncharged dopamine analogs with the D-2 dopaminergic receptor

Raye Ann Wallace, Tahira Farooqui, Lane Wallace, Jeff Ares, Chang Yu An, Duane Miller, Norman Uretsky

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The purpose of this study was to determine if structural analogs of dopamine in which the side chain nitrogen has been replaced by a permanently uncharged monomethylsulfide, monomethylselenide or sulfoxide group are capable of binding to the striatal D-2 dopamine receptor and acting as agonists at this receptor. All the permanently uncharged dopamine analogs were found to bind to the D-2 dopamine receptor as evidenced by their abilities to inhibit significantly [3H]spiperone binding to striatal homogenates. However, the inhibition of [3H]spiperone binding by the uncharged dopamine analogs was incomplete and was almost abolished by the addition of NaCl (125 mM) to the incubation medium or by the addition of dopamine or quinpirole at a concentration that saturates the high-affinity state of the D-2 dopamine receptor. These effects of NaCl, dopamine and quinpirole suggest that the uncharged dopamine analogs bind primarily to the high-affinity state of the D-2 dopamine receptor. Whether the uncharged monomethylsulfide and sulfoxide analogs could function as dopamine agonists at the striatal D-2 dopamine receptor was assessed by determining the abilities of these compounds to inhibit the K+-evoked release of [3H]acetylcholine from striatal slices. Both the monomethylsulfide and sulfoxide analogs inhibited the K+evoked release of [3H]acetylcholine, but this inhibitory effect does not appear to be due to the activation of the D-2 dopamine receptor since it was not reversed by the selective D-2 dopamine antagonist, sulpiride. Additionally, the uncharged monomethylsulfide and sulfoxide dopamine analogs were found to antagonize the ability of apomorphine to inhibit the K+ evoked release of [3H]acetylcholine, but this antagonistic effect does not appear to be due to the reversible blockade of the D-2 dopamine receptor since it was not reduced by increasing the concentration of apomorphine. Therefore, while the permanently uncharged analogs of dopamine appear to bind to the high-affinity state of the D-2 dopamine receptor, they are not dopamine agonists or antagonists at the striatal D-2 dopamine receptor involved in regulating the release of acetylcholine. These results suggest that a positive charge may be a requirement for the activation of the striatal D-2 dopamine receptor.

Original languageEnglish (US)
Pages (from-to)2077-2084
Number of pages8
JournalBiochemical Pharmacology
Volume37
Issue number10
DOIs
StatePublished - May 15 1988
Externally publishedYes

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Dopamine Receptors
sulfoxide
Dopamine
Corpus Striatum
Acetylcholine
Quinpirole
Spiperone
Dopamine Antagonists
Apomorphine
Dopamine Agonists
Chemical activation
Sulpiride
Nitrogen

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

Cite this

Interaction of permanently uncharged dopamine analogs with the D-2 dopaminergic receptor. / Wallace, Raye Ann; Farooqui, Tahira; Wallace, Lane; Ares, Jeff; Yu An, Chang; Miller, Duane; Uretsky, Norman.

In: Biochemical Pharmacology, Vol. 37, No. 10, 15.05.1988, p. 2077-2084.

Research output: Contribution to journalArticle

Wallace, RA, Farooqui, T, Wallace, L, Ares, J, Yu An, C, Miller, D & Uretsky, N 1988, 'Interaction of permanently uncharged dopamine analogs with the D-2 dopaminergic receptor', Biochemical Pharmacology, vol. 37, no. 10, pp. 2077-2084. https://doi.org/10.1016/0006-2952(88)90559-X
Wallace, Raye Ann ; Farooqui, Tahira ; Wallace, Lane ; Ares, Jeff ; Yu An, Chang ; Miller, Duane ; Uretsky, Norman. / Interaction of permanently uncharged dopamine analogs with the D-2 dopaminergic receptor. In: Biochemical Pharmacology. 1988 ; Vol. 37, No. 10. pp. 2077-2084.
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