Effects of Dopaminergic Transmission Interruption on the D2 Receptor Isoforms in Various Cerebral Tissues

Martres, Marie‐Pascale; Sokoloff, Pierre; Giros, Bruno; Jc, Schwartz

doi:10.1111/j.1471-4159.1992.tb09770.x

Cited by 50 publications

(18 citation statements)

References 32 publications

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“…3B). Parallelism was check for each amplification, thus the ratio of D2 receptor mRNA isoforms was calcu lated under adequate conditions in our experiments, as done previously [29], Figure 3C indicates that the amplification of D2S and D2L isoforms was not dependent upon cDNA concentra tion. Ratios of both amplified forms were not changed with the initial amount of total cDNA in the PCR tube.…”

Section: Amplification O F D> Dopamine Receptor Mrnasmentioning

confidence: 58%

Decreased Expression of the Two D2 Dopamine Receptor Isoforms in Bromocriptine-Resistant Prolactinomas

et al. 1994

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Bromocriptine or other dopamine agonists are usually effective for the treatment of prolactin-secreting adenomas. Five to 18% of prolactinomas, however, do not respond to such therapy. We have shown previously that such resistance to bromocriptine correlates with reduced binding to the D₂ receptor subtype of dopamine, the major PRL inhibiting factor. In the present work, we demonstrated that reduced binding actually corresponds to decreased expression of the gene coding for the D₂ receptor in the pituitary from bromocriptine-resistant patients, as shown by 4-fold lower levels of the corresponding mRNAs compared to those coding for actin. The existence of two D₂ receptor isoforms, D₂S and D₂L generated by alternative splicing, has been described in several tissues, including the pituitary. Both are negatively coupled to adenylyl cyclase and inhibit prolactin secretion, but, in addition, the shortest one (D₂S) is more efficiently coupled to phospholipase C. Consequently, we also investigated whether expression of a particular D₂ receptor isoform was preferentially affected in resistant adenomas. The proportion of messengers corresponding to the short receptor isoform (D₂S) was lower in resistant compared to responsive adenomas: D₂S/D₂L = 0.74 ± 0.08 and 1.00 ± 0.07, respectively. In parallel, much lower levels of D₂ receptor mRNAs were found in growth hormone-secreting adenomas, with a D₂S/D₂L ratio comparable to those of both normal human pituitary and bromocriptine-sensitive prolactinomas (1.05 ± 0.11). Thus, resistance to bromocriptine therapy seems to involve defects in D₂ dopamine receptor expression and possibly in posttranscriptional splicing.

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Section: Amplification O F D> Dopamine Receptor Mrnasmentioning

confidence: 58%

Decreased Expression of the Two D2 Dopamine Receptor Isoforms in Bromocriptine-Resistant Prolactinomas

et al. 1994

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“…According to Martres et al [66], treatment with a dopamine antagonist preferably increased the shorter isoform (D2S) in the brain or the pituitary gland. Hajnal et al [15] reported D2 receptors to be efficient inhibitors reducing sucrose intake in rats, during exposure to high sucrose intake.…”

Section: Discussionmentioning

confidence: 99%

Effects of Ovariectomy and 17β-Estradiol Replacement on Dopamine D2 Receptors in Female Rats: Consequences on Sucrose, Alcohol, Water Intakes and Body Weight

Bâ¹,

Silué²,

Bamba³

et al. 2018

JBBS

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Background: Mechanisms underlying overeating-induced obesity in postmenopausal woman include functional lack of 17β-estradiol dysregulating dopamine D2 receptors, thereby inducing food addiction, glucose craving or alcohol dependence through reward circuitry. This study aimed at further understanding 17β-estradiol and dopamine D2 receptors interferences in the etiology of woman obesity. Method: Seventy-two Wistar female rats weighing 200 -205 g, individually-housed, were divided into non-ovariectomized control (C = 6 groups) and ovariectomized rats (OVX = 6 groups) which were concurrently subjected to the following treatments: Non-drug-treated (DMSO vehicle), 17β-estradiol (E2, 5 µg/kg, s.c.), sulpiride (SUL, 20 mg/kg, i.p.), bromocriptine (BR, 0.1 mg/kg, i.p.), E2 + SUL or E2 + BR, designating the 6 constitutive groups of either control or ovariectomy. Within each experimental group, consumption of different solutions (10% alcohol, 10% sucrose and water) as well as food intake and body weight were daily measured, for 10 consecutive days. Results: This study indicated that D2S was a specific inducer of alcohol and food intakes, but reduced sugar consumption. In addition, 17β-estradiol regulated the body weight set point, modulating D2S functions towards increased food intake at lower weights and decreased food intake at higher weights. D2S met the slow genomic actions induced by 17β-estradiol. Conversely, D2L inhibited alcohol and food intakes, but induced specifically sugar consumption, thereby regulating blood glucose levels and promoting energy expenditure in reducing body weight. Indeed, 17β-estradiol exerted a tonic inhibition on D2L which was released by OVX, exacerbating sugar intake and increasing body weight. D2L mediated the rapid metabolic effects of that activation of the mostly expressed presynaptically D2S-class autoreceptors decreased dopamine release stimulating food intake, whereas activation of the predominantly postsynaptic isoform D2L receptors increased dopamine activity inhibiting food intake. Our studies indicated that 17β-estradiol acted on the two types of D2 receptors showing opposite functions to equilibrate energy intake vs. expenditure for weight set point regulation. Our data also supported biochemical findings reporting that 17β-estradiol induced D2 genes transcriptional regulation, thereby involving both types of D2 receptors in the etiology of obesity. The combined dysregulated effects of D2L and D2S receptors, as 17β-estradiol was lacking, would be causal factors underlying the etiology of obesity.

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“…[10][11][12]. The process of neuroleptic-induced upregulation in receptor density has recently been shown to be associated with an increased D2 receptor mRNA level (13)(14)(15)(16). In contrast, no tolerance to the antipsychotic effects of these drugs seems to develop (17), suggesting that a subpopulation of D2-like receptors subserving the antipsychotic effects is not subject to antagonistinduced upregulation.…”

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confidence: 99%

A paradoxical regulation of the dopamine D3 receptor expression suggests the involvement of an anterograde factor from dopamine neurons.

Lévesque

Martres

Díaz

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

155

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The effects of interruption of dopaminergic transmission or sustained blockade of dopamine receptors by neuroleptics on the dopamine D3 receptor in the shell of the nucleus accumbens were investigated in rats. In this brain area the D3 receptor is abundant and may mediate antipsychotic drug effects. The D3 receptor density and mRNA abundance were evaluated with 7-[3H]hydroxy-N,N-di-n-propyl-2-aminotetralin and by quantitative PCR or image analysis ofin situ hybridization signals, respectively. Unilateral dopamine neuron degeneration by 6-hydroxydopamine or sections triggered, after a few days, a marked decrease (up to 50%) in D3 receptor binding and mRNA in the nucleus accumbens. In contrast, a 2-week treatment with the neuroleptic haloperidol (20 mg/kg) had no effect on D3 receptor density and mRNA but enhanced D2 receptor density and mRNA level by >50%. In addition, tolerance to the haloperidol-induced change of neurotensin mRNA mediated by the D2 receptor developed, but there was no tolerance to the opposite change mediated by the D3 receptor. Reserpine, a monoamine-depleting drug with antipsychotic activity, did not modify D3 receptor mRNA. These observations reinforce the idea that the D3 receptor may be an important target for neuroleptics whose antipsychotic actions, but not extrapyramidal motor actions, do not display tolerance. The D3 receptor mRNA level was also decreased by a unilateral injection in dopamine cell body areas of colchicine, a drug blocking the anterograde axonal transport, or by baclofen, a type A -aminobutyric acid receptor agonist reducing dopamine neuron activity, but not by sustained blockade of Dil-like and D2-like, neurotensin, or cholecystokinin receptors. We therefore propose that an anterograde factor present in mesolimbic dopaminergic neurons, but distinct from dopamine and known peptide cotransmitters, plays a positive role on transcription of the D3 receptor gene.The dopamine (DA) D3 and D4 receptors, two receptors displaying similarities with the DA D2 receptor, have been recently identified. Their high sequence homology (1, 2), similar coupling to guanine nucleotide binding proteins (3-5), and recognition by antipsychotic drugs (1, 2, 6, 7) have raised questions regarding the functional significance of this diversity.Receptor diversity may allow a single neurotransmitter to exert distinct influences on various target neurons. In this respect, D3 and, even more, D4 receptors seem to be expressed in much more restricted brain areas and in distinct neuronal populations as compared to the D2 receptor (1, 2, 8). The D4 receptor, however, seems to mediate, like the D2 receptor, inhibition of adenylyl cyclase (5). In the case of the D3 recepThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.tor, the signaling system in cerebral neurons remains to be identified but its stimulation may trigger responses opposite to tho...

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Effects of Dopaminergic Transmission Interruption on the D₂ Receptor Isoforms in Various Cerebral Tissues

Cited by 50 publications

References 32 publications

Decreased Expression of the Two D<sub>2</sub> Dopamine Receptor Isoforms in Bromocriptine-Resistant Prolactinomas

Decreased Expression of the Two D<sub>2</sub> Dopamine Receptor Isoforms in Bromocriptine-Resistant Prolactinomas

Effects of Ovariectomy and 17<i>β</i>-Estradiol Replacement on Dopamine D2 Receptors in Female Rats: Consequences on Sucrose, Alcohol, Water Intakes and Body Weight

A paradoxical regulation of the dopamine D3 receptor expression suggests the involvement of an anterograde factor from dopamine neurons.

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Effects of Dopaminergic Transmission Interruption on the D2 Receptor Isoforms in Various Cerebral Tissues

Cited by 50 publications

References 32 publications

Decreased Expression of the Two D<sub>2</sub> Dopamine Receptor Isoforms in Bromocriptine-Resistant Prolactinomas

Decreased Expression of the Two D<sub>2</sub> Dopamine Receptor Isoforms in Bromocriptine-Resistant Prolactinomas

Effects of Ovariectomy and 17&lt;i&gt;β&lt;/i&gt;-Estradiol Replacement on Dopamine D2 Receptors in Female Rats: Consequences on Sucrose, Alcohol, Water Intakes and Body Weight

A paradoxical regulation of the dopamine D3 receptor expression suggests the involvement of an anterograde factor from dopamine neurons.

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Effects of Dopaminergic Transmission Interruption on the D₂ Receptor Isoforms in Various Cerebral Tissues

Effects of Ovariectomy and 17<i>β</i>-Estradiol Replacement on Dopamine D2 Receptors in Female Rats: Consequences on Sucrose, Alcohol, Water Intakes and Body Weight