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  • Title: Dopamine D2 receptors in brain and anterior pituitary recognize agonist and antagonist actions of (-)-3-PPP.
    Author: George SR, Watanabe M, Seeman P.
    Journal: J Neural Transm; 1985; 64(1):13-33. PubMed ID: 2933489.
    Abstract:
    (-)-3-PPP, is a unique dopamine analogue, reported to have selective agonist actions at dopamine autoreceptors and antagonist actions at postsynaptic receptors. The interactions of D2 dopamine receptors with (-)-3-PPP in vitro were examined, using [3H]spiperone to label D2 receptors in brain regions containing both pre- and postsynaptic D2 receptors (caudate nucleus, corpus striatum) and a region containing nonsynaptic D2 receptors (anterior pituitary). In the absence of sodium ions, (-)-3-PPP detected D2 receptors in high- and low-affinity states in all regions examined, as is typical of dopamine agonists. That these two subpopulations of (-)-3-PPP-detected sites were dopaminergic in nature was assured by precluding [3H]spiperone binding to serotonergic receptors. In the presence of sodium ions, there was a significant increase in the affinity of some D2 receptors detected by (-)-3-PPP, and (-)-3-PPP in the presence of sodium was unable to discriminate between the two D2 affinity states in pituitary and striatum. The addition of guanine nucleotide led to (-)-3-PPP recognition of a single D2 binding site; the enhanced affinity of D2 receptors for (-)-3-PPP in the presence of sodium was retained in the presence of guanine nucleotide. These in vitro characteristics of (-)-3-PPP recognition of dopamine D2 receptor binding sites, when compared with dopamine and spiperone are seen to have clear features of both typical agonist and antagonist interactions with D2 receptors in both brain and pituitary.
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