Agonist and antagonist properties of benzazepine and thienopyridine derivatives at the D1 dopamine receptor

O’Boyle, Kathy M.; Gaitanopoulos, Dimitri E.; Brenner, Martin; Waddington, John L.

doi:10.1016/0028-3908(89)90036-1

Cited by 126 publications

(53 citation statements)

References 22 publications

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“…Similarly, H89 reduced SKF induction of ER transcription activity in MCF-7 cells (27). These reports are consistent with the ability of SKF to stimulate adenylate cyclase and cAMP production via the dopamine D1 receptor (46,47), and it is possible that in these cell models ER␣ transactivation by SKF is at least partially cAMP/protein kinase A-dependent and/or that H89 is inhibiting the activity of other signaling pathways able to cross-talk with ER␣ or AP-1. Indeed, whereas H89 effectively inhibits protein kinase A, it also blocks the activity of other kinases including protein kinase B (Akt) and mitogen-and stress-activated protein kinase-1 (72).…”

Section: Discussionsupporting

confidence: 73%

“…In contrast, maximal dopamine induction of ER-directed gene expression occurs at 100 -250 M (23,30,31), suggesting that SKF-82958 is a more potent activator of this response. However, the potency (K m ) and maximum efficacy of SKF-82958 induction of cAMP are similar to that for dopamine in rat brain striatum after treatment in vivo (46). This discrepancy suggested that there may be mechanistic differences in the ability of SKF-82958 and dopamine to stimulate ER␣ transcriptional activity.…”

Section: Methodsmentioning

confidence: 59%

“…The molecular mechanisms of dopamine and dopamine receptor action have therefore been extensively studied, and these efforts have been aided by the identification of high affinity and potent ligands for dopamine receptors. One such compound, SKF-82958 (SKF), is a full dopamine D1 subtype-selective receptor agonist with greater potency than dopamine (46,47). SKF has also been shown to stimulate the transcriptional activity of ER␣ in SK-N-SH neuroblastoma and MCF-7 breast cancer cells (27,37).…”

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confidence: 99%

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SKF-82958 Is a Subtype-selective Estrogen Receptor-α (ERα) Agonist That Induces Functional Interactions between ERα and AP-1

Walters

Dutertre

Smith

2002

Journal of Biological Chemistry

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The transcriptional activity of estrogen receptors (ERs) can be regulated by ligands as well as agents such as dopamine, which stimulate intracellular signaling pathways able to communicate with these receptors. We examined the ability of SKF-82958 (SKF), a previously characterized full dopamine D1 receptor agonist, to stimulate the transcriptional activity of ER␣ and ER␤. Treatment of HeLa cells with SKF-82958 stimulated robust ER␣-dependent transcription from an estrogen-response element-E1b-CAT reporter in the absence of estrogen, and this was accompanied by increased receptor phosphorylation. However, induction of ER␤-directed gene expression under the same conditions was negligible. In our cell model, SKF treatment did not elevate cAMP levels nor enhance transcription from a cAMPresponse element-linked reporter. Control studies revealed that SKF-82958, but not dopamine, competes with 17␤-estradiol for binding to ER␣ or ER␤ with comparable relative binding affinities. Therefore, SKF-82958 is an ER␣-selective agonist. Transcriptional activation of ER␣ by SKF was more potent than expected from its relative binding activity, and further examination revealed that this synthetic compound induced expression of an AP-1 target gene in a tetradecanoylphorbol-13-acetate-response element (TRE)-dependent manner. A putative TRE site upstream of the estrogen-response element and the amino-terminal domain of the receptor contributed to, but were not required for, SKF-induced expression of an ER␣-dependent reporter gene. Overexpression of the AP-1 protein c-Jun, but not c-Fos, strongly enhanced SKF-induced ER␣ target gene expression but only when the TRE was present. These studies provide information on the ability of a ligand that weakly stimulates ER␣ to yield strong stimulation of ER␣-dependent gene expression through cross-talk with other intracellular signaling pathways producing a robust combinatorial response within the cell.The effects of estrogens are mediated by the products of two separate genes, one for estrogen receptor-␣ (ER␣) 1 and another for ER␤. Both are members of the nuclear receptor superfamily of ligand-activated transcription factors. The mechanisms by which ERs activate target gene expression in response to estrogen signaling have been the subject of intense investigation since their respective cDNAs were cloned (1, 2). Because of the relatively recent identification of ER␤, the bulk of our knowledge regarding the genomic effects of estrogens is derived from ER␣ studies. For instance, upon binding to 17␤-estradiol (E 2 ), ER␣ undergoes a series of biochemical alterations including increased phosphorylation and conformational changes as well as homodimerization and binding of the receptor to its target DNA sequence, the estrogen-response element (ERE; see Refs. 3-5). ER␤ also undergoes conformational changes in response to ligand binding (6, 7) and is phosphorylated in vivo (8). With respect to DNA binding, ER␤ binds to the same consensus ERE that ER␣ does, although the latter receptor has an ϳ4-fold ...

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Section: Discussionsupporting

confidence: 73%

Section: Methodsmentioning

confidence: 59%

mentioning

confidence: 99%

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SKF-82958 Is a Subtype-selective Estrogen Receptor-α (ERα) Agonist That Induces Functional Interactions between ERα and AP-1

Walters

Dutertre

Smith

2002

Journal of Biological Chemistry

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“…1~3, both SKF81297 and R-(-)-TNPA showed relatively time-dependent inhibition in the CA secretory responses evoked by cholinergic stimulation and membrane depolarization form the perfused rat adrenal glands. Generally, the prototypical dopamine D1 receptor agonist, SKF81297, and the dopamine D1 receptor antagonist, R(+)-SCH23390, have been widely used to characterize the functional role of dopamine D1 receptors in both in vitro as well as in vivo paradigms (O'Boyle et al, 1989;Gessa et al, 1991;Lewis et al, 1998), Therefore, it was likely of interest to examine effects of R(+)-SCH23390 (a selective D1 antagonist) and S(-)-raclopride (a selective D2 antagonist), on the CA secretion evoked by evoked by ACh, high K + , DMPP and McN-A-343 from the isolated perfused rat adrenal glands.…”

Section: Effects Of Skf81297 and R-(-)-tnpa On The Ca Secretion Evokementioning

confidence: 99%

Roles of Dopaminergic D₁and D₂Receptors in Catecholamine Release from the Rat Adrenal Medulla

Baek

Seo

Lim

2008

Korean J Physiol Pharmacol

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The aim of the present study was designed to establish comparatively the inhibitory effects of D1-like and D2-like dopaminergic receptor agonists, SKF81297 and R(-)-TNPA on the release of catecholamines (CA) evoked by cholinergic stimulation and membrane depolarization from the isolated perfused model of the rat adrenal medulla. SKF81297 (30μM) and R-(-)-TNPA (30μM) perfused into an adrenal vein for 60 min, produced great inhibition in the CA secretory responses evoked by ACh (5.32×10

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“…We investigated the behavioral effects of various dopamine agonists, the nonselective dopamine agonist apomorphine, the dopamine D1-receptor agonist SKF 82958 (14) and the dopamine D2-receptor agonist quinpirole in MPTP-lesioned parkinsonian cynomolgus monkeys, with regard to the induction of hyperactivity such as excitability, irritability and aggressiveness.…”

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confidence: 99%

Behavioral Involvement of Central Dopamine and D2 Receptors in l-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-Lesioned Parkinsonian Cynomolgus Monkeys

Akai¹,

Ozawa²,

Yamaguchi³

et al. 1995

Japanese Journal of Pharmacology

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ABSTRACT-To clarify the roles of dopamine D, and D2 receptors in behavioral symptoms of Parkinson's disease, antiparkinsonian effects of various dopamine agonists in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian monkeys were investigated with regard to induction of hyperactivity such as excitability, irritability and aggressiveness. The non-selective dopamine agonist apomorphine ameliorated the parkinsonism, but induced marked hyperactivity dose-dependently. Pretreatment with either the dopamine D, antagonist SCH 23390 or the dopamine D2 antagonist sulpiride markedly suppressed the apomorphine-induced hyperactivity with slight attenuation of the antiparkinsonian effects. Both the dopamine D2-receptor agonist quinpirole and the dopamine D,-receptor agonist SKF 82958 ameliorated the parkinsonism in a dose-dependent manner with a slight induction of hyperactivity. Combination treatment of a threshold dose of quinpirole with that of SKF 82958 augmented the antiparkinsonian effects without a marked induction of hyperactivity. However, the combination treatment at higher doses induced marked hyperactivity accompanied by augmented antiparkinsonian effects. These results suggest that stimulation of either central dopamine D, or D2 receptors is requisite for the antiparkinsonian effects and concurrent strong stimulation of both central dopamine D, and D2 receptors causes marked hyperactivity which may be predictive of dopaminergic psychiatric side effects.

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Agonist and antagonist properties of benzazepine and thienopyridine derivatives at the D1 dopamine receptor

Cited by 126 publications

References 22 publications

SKF-82958 Is a Subtype-selective Estrogen Receptor-α (ERα) Agonist That Induces Functional Interactions between ERα and AP-1

SKF-82958 Is a Subtype-selective Estrogen Receptor-α (ERα) Agonist That Induces Functional Interactions between ERα and AP-1

Roles of Dopaminergic D₁and D₂Receptors in Catecholamine Release from the Rat Adrenal Medulla

Behavioral Involvement of Central Dopamine and D2 Receptors in l-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-Lesioned Parkinsonian Cynomolgus Monkeys

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Agonist and antagonist properties of benzazepine and thienopyridine derivatives at the D1 dopamine receptor

Cited by 126 publications

References 22 publications

SKF-82958 Is a Subtype-selective Estrogen Receptor-α (ERα) Agonist That Induces Functional Interactions between ERα and AP-1

SKF-82958 Is a Subtype-selective Estrogen Receptor-α (ERα) Agonist That Induces Functional Interactions between ERα and AP-1

Roles of Dopaminergic D1and D2Receptors in Catecholamine Release from the Rat Adrenal Medulla

Behavioral Involvement of Central Dopamine and D2 Receptors in l-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-Lesioned Parkinsonian Cynomolgus Monkeys

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Roles of Dopaminergic D₁and D₂Receptors in Catecholamine Release from the Rat Adrenal Medulla