Comparison of [<sup>3</sup>H]Phosphatidylinositol and [<sup>3</sup>H]Phosphatidylinositol 4,5‐Bisphosphate Hydrolysis in Postmortem Human Brain Membranes and Characterization of Stimulation by Dopamine D1 Receptors

Pacheco, Mary A.; Jope, Richard S.

doi:10.1046/j.1471-4159.1997.69020639.x

Cited by 53 publications

(37 citation statements)

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“…11). One possibility is that dopamine acts on a putative PLC-linked D1 class DAR (9,10,60). Indeed, SKF83959, a specific agonist for this putative PLC-linked D1 class DAR (11), induced Ca 2ϩ release from intracellular stores in MSN (Fig.…”

Section: Discussionmentioning

confidence: 97%

Dopamine Receptor-mediated Ca2+ Signaling in Striatal Medium Spiny Neurons

Tang

Bezprozvanny

2004

Journal of Biological Chemistry

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Inositol 1,4,5-trisphosphate (InsP 3 ) and cAMP are the two second messengers that play an important role in neuronal signaling. Here, we investigated the interactions of InsP 3 -and cAMP-mediated signaling pathways activated by dopamine in striatal medium spiny neurons (MSN). We found that in ϳ40% of the MSN, application of dopamine elicited robust repetitive Ca 2؉ transients (oscillations). In pharmacological experiments with specific agonists and antagonists, we found that the observed Ca 2؉ oscillations were triggered by activation of D1 class dopamine receptors (DARs). We further demonstrated that activation of phospholipase C was required for induction of dopamine- Dopamine is an important transmitter and neuromodulator in the brain. The cellular mechanisms by which dopamine affects neuronal function are only beginning to be elucidated (1, 2). Striatal medium spiny neurons (MSN) 1 express multiple subtypes of dopamine receptors (DARs) (3-5). On the basis of their molecular structure and pharmacological properties, DARs are divided into the D1 class (D1R and D5R) and D2 class (D2R, D3R, and D4R) (6). D1 class DARs are coupled to G s/olf , activation of adenylyl cyclase, and cAMP production (3). Activation of D2 class DARs has dual effects of inhibiting cAMP production (3) and activating phospholipase C␤ (PLC␤) (7). A putative D1 class DAR subtype coupled to PLC activation and phosphatidylinositol 4,5-diphosphate hydrolysis, but not to cAMP production, has been postulated (8 -10), but has not yet been isolated or cloned. Recently, a specific agonist for this receptor (SKF83959) was identified (11). The D1R-binding protein calcyon has been isolated by yeast two-hybrid methods (12). Association of D1/D5 receptors with calcyon enables coupling of D1/D5 receptors with G q/11 , resulting in PLC activation and inositol 1,4,5-trisphosphate (InsP 3 ) generation (12, 13). Cross-talk between cAMP and Ca 2ϩ signaling pathways plays an important role in dopaminergic signaling in the neostriatum (1). Activation of D1 class DARs enhances L-type Ca 2ϩ channel activity (14 -16) and currents via the ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (17) and the N-methyl-D-aspartic acid (NMDA) receptor (18,19). In contrast, activation of D2 class DARs reduces L-type Ca 2ϩ currents (7) and NMDA receptor activity (20). D1/D5 receptormediated facilitation of L-type Ca 2ϩ channels and AMPA and NMDA receptors results from increased phosphorylation of these channels by protein kinase A (PKA) (16, 21) and decreased dephosphorylation of these channels by protein phosphatase-1 (PP1) (17,22,23). DARPP-32 (dopamine-and cAMPregulated phosphoprotein of M r 32,000) (24, 25) is partly responsible for inhibition of PP1 activity following activation of D1/D5 receptors (26). DARPP-32 phosphorylated by PKA at a single threonine residue (Thr-34) is transformed into a potent inhibitor of PP1, which in turn regulates the phosphorylation state of many neurotransmitter receptors and voltage-gated ion channels (1).The type 1 inos...

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Section: Discussionmentioning

confidence: 97%

Dopamine Receptor-mediated Ca2+ Signaling in Striatal Medium Spiny Neurons

Tang

Bezprozvanny

2004

Journal of Biological Chemistry

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“…Although a number of studies have found that G ␣q couples the dopamine receptor to PLC (Felder et al, 1989;Undie and Friedman, 1990;Pacheco and Jope, 1997), the recent identification of a selective agonist, SKF83959 (Panchalingam and Undie, 2001;Jin et al, 2003), for this pathway has allowed the detailed investigation of signal transduction and function of this dopamine receptor. The present data demonstrate that activation of the PI-linked D 1 dopamine receptor differentially regulates the cdk5 and CaMK II pathways.…”

Section: Discussionmentioning

confidence: 99%

“…activation of phospholipase C␤ (PLC␤), which hydrolyzes phosphatidylinositol (PI) into diacylglycerol and inositol trisphosphate (IP 3 ) (Felder et al, 1989;Undie and Friedman, 1990;Pacheco and Jope, 1997). IP 3 is an important second messenger that elicits the release of calcium from intracellular stores.…”

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confidence: 99%

Regulation of Cyclin-Dependent Kinase 5 and Calcium/Calmodulin-Dependent Protein Kinase II by Phosphatidylinositol-Linked Dopamine Receptor in Rat Brain

Zhen

Goswami²,

Abdali³

et al. 2004

Mol Pharmacol

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A brain dopamine receptor that modulates phosphatidylinositol (PI) metabolism via the activation of phospholipase C␤ (PLC␤) has been described previously. The present study aims to define the downstream signaling cascade initiated by the PIlinked dopamine receptor. Incubation of rat brain frontal cortical slices with 6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF83959), a recently identified selective agonist of the PI-linked D 1 -like dopamine receptor, elicited transient time-and dose-dependent stimulations of cyclin-dependent kinase 5 (cdk5) and calcium/calmodulin-dependent protein kinase II (CaMK II) activities. The stimulation of these kinases is blocked by 20 M R-(ϩ) -7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH23390) or the PLC␤ antagonist 1-[6-[[17␤-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U-73122) and is attenuated by the protein kinase inhibitor calphostin C or by the intracellular calcium chelator BAPTA, indicating that SKF83959 stimulates cdk5 and CaMK II activities via a PI-linked D 1 -like dopamine receptor, and PLC␤ and is dependent on protein kinase C and calcium. Although cdk5 and CaMK II are physically associated in native brain tissue, no change in this association was observed in response to SKF83959 stimulation or to the inhibition of either cdk5 by roscovitine or of CaMK by 2-[N-(2-hydroxyethyl)]-N-(4-methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-Nmethylbenzylamine) (KN93), suggesting that SKF83959-mediated stimulation of cdk5 or CaMK II is independent of the other kinase and that the association of the two kinases is not modulated by change of kinase activity. Moreover, we found that cdk5 phosphorylates dopamine and cAMP-regulated phosphoprotein at Thr75, whereas CaMK II is responsible for the activation of cAMP response element-binding protein in response to SKF83959 stimulation. The present data provide the first insight into the signaling mechanism for the PI-linked dopamine receptor. This information, in turn, may help in exploring the functional consequences of stimulation of this brain receptor.

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“…These results strongly support the idea that the enhancement of dopamine-induced Ca 2+ responses after exposure to BPA could lead to an increase in the excitability of the central dopaminergic neurons. It has been reported that stimulation of dopamine D1 receptor increases intracellular Ca 2+ concentration via activation of phospholipase C-inositol-1,4,5-trisphosphate signaling pathway (Pacheco and Jope, 1997;Jin et al, 2003). Dopamine-induced Ca 2+ responses are also modulated by dopamine D2 receptor (Zhu et al, 1997;Takeuchi et al, 2002).…”

Section: Activation Of Astrocytes By Bpamentioning

confidence: 99%

Effects of Prenatal and Neonatal Exposure to Bisphenol A on the Development of the Central Nervous System

Mizuo¹,

Narita²,

Miyagawa³

et al. 2010

Biomolecules and Therapeutics

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-Bisphenol A (BPA) is one of the most common endocrine disrupters. In the last decade, the number of studies concerning the effects of chronic treatment with BPA on the development of the central nervous system (CNS) has increased. However, little is known about the effects of chronic exposure to BPA on higher brain functions such as memory or psychomotor functions. Here, we report our following findings: (1) Prenatal and neonatal exposure to BPA enhances psychostimulant-induced rewarding effects, results in the up-or downregulation of dopamine receptors, causes memory impairment, and decreases choline acetyltransferase (ChAT) activity. (2) BPA activates astrocytes in vivo and in vitro. These findings suggest that prenatal and neonatal exposure to BPA affects the development of the CNS.

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Comparison of [³H]Phosphatidylinositol and [³H]Phosphatidylinositol 4,5‐Bisphosphate Hydrolysis in Postmortem Human Brain Membranes and Characterization of Stimulation by Dopamine D1 Receptors

Cited by 53 publications

References 15 publications

Dopamine Receptor-mediated Ca2+ Signaling in Striatal Medium Spiny Neurons

Dopamine Receptor-mediated Ca2+ Signaling in Striatal Medium Spiny Neurons

Regulation of Cyclin-Dependent Kinase 5 and Calcium/Calmodulin-Dependent Protein Kinase II by Phosphatidylinositol-Linked Dopamine Receptor in Rat Brain

Effects of Prenatal and Neonatal Exposure to Bisphenol A on the Development of the Central Nervous System

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Comparison of [3H]Phosphatidylinositol and [3H]Phosphatidylinositol 4,5‐Bisphosphate Hydrolysis in Postmortem Human Brain Membranes and Characterization of Stimulation by Dopamine D1 Receptors

Cited by 53 publications

References 15 publications

Dopamine Receptor-mediated Ca2+ Signaling in Striatal Medium Spiny Neurons

Dopamine Receptor-mediated Ca2+ Signaling in Striatal Medium Spiny Neurons

Regulation of Cyclin-Dependent Kinase 5 and Calcium/Calmodulin-Dependent Protein Kinase II by Phosphatidylinositol-Linked Dopamine Receptor in Rat Brain

Effects of Prenatal and Neonatal Exposure to Bisphenol A on the Development of the Central Nervous System

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Comparison of [³H]Phosphatidylinositol and [³H]Phosphatidylinositol 4,5‐Bisphosphate Hydrolysis in Postmortem Human Brain Membranes and Characterization of Stimulation by Dopamine D1 Receptors