Potentiation of Prolactin Secretion following Lactotrope Escape from Dopamine Action

Hernández, M E; Hernandez, Maria; Dı́az-Muñoz, Mauricio; Clapp, Carmen; Escalera, Gonzálo Martínez de la

doi:10.1159/000054457

Cited by 10 publications

(4 citation statements)

References 82 publications

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“…Even though the molecular bases for the stimulation of Ca 2+ currents remain to be fully determined, these channels appear to be a major control point in the regulation of hormone secretion, and could be responsible for the DA-escape facilitation of secretagogue-induced PRL secretion. From the results in this and the companion paper [44], we propose that the escape from the tonic DA action recruits voltage-dependent Ca 2+ channels. Consequently, after DA washout, a greater number of HVA, L-type Ca 2+ channels are available to conduct Ca 2+ in response to a TRH-induced depolarization.…”

Section: Discussionmentioning

confidence: 56%

“…Phosphorylation of α1 and β subunits of voltage-dependent calcium channels by protein kinases A and C [40, 41]is known to enhance their opening probability, leading to a larger Ca 2+ influx into the cell during the open state [42, 43]. Along this line, we have recently observed that DA withdrawal increases the rate of phosphorylation of the α1 subunit of voltage-dependent calcium channels in cultured pituitary lactotropes and GH 4 C 1 /D 2 -DAR cells, within a time frame that also parallels the rapid increase in Ca 2+ conductance [44]. …”

Section: Discussionmentioning

confidence: 99%

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Potentiation of Prolactin Secretion following Lactotrope Escape from Dopamine Action

et al. 1999

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Hypothalamic dopamine (DA) tonically inhibits prolactin (PRL) release from the anterior pituitary gland. Transient escapes from this DA tone elicit a pronounced potentiation of the PRL-releasing action of secretagogues such as thyrotropin-releasing hormone (TRH). Previous evidence has suggested that modulation of Ca²⁺ channels can be involved in this potentiation. With a lactotropic cell line (GH₄C₁) expressing human D₂-DA receptors, we tested the hypothesis that a brief escape from the tonic inhibitory action of DA triggers a facilitation of Ca²⁺ influx through Ca²⁺ channels. We initially found that in these cells, DA effectively and reversibly inhibited PRL secretion, and reversibly enhanced an inwardly rectifying K⁺ current. The effects of DA administration and withdrawal on Ca²⁺ currents were examined using the patch-clamp technique in the whole-cell configuration and Ba²⁺ as a divalent charge carrier through Ca²⁺ channels. Macroscopic Ba²⁺ currents were significantly decreased by short term (1–10 min) applications of DA (500 nM), which further declined following 24 h of constant exposure to DA. After DA removal, a biphasic facilitation of the density of Ba²⁺ currents was observed. An initial 2-fold enhancement of conductance was detected between 10 and 40 min, followed by a second facilitation of the same magnitude observed 24 h after DA withdrawal. The present results directly demonstrate that dissociation of DA from D₂-receptors expressed in GH₄C₁ lactotrope cells causes an increase of high-voltage-activated Ca²⁺ channel function, which may play an important role in the cross-talking amplification of endocrine cascades such as that involved in the TRH-induced PRL-release potentiating action of DA withdrawal.

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Potentiation of Prolactin Secretion following Lactotrope Escape from Dopamine Action

et al. 1999

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“…currents in diverse human tissues and cell lines: heart, neuroblastoma, T-cells, and endocrine cells (5)(6)(7)(8)(9)(10). Dual modulation by PKC is often observed with activation followed by, or concomitant with, inhibition (5,10).…”

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A Novel Long N-terminal Isoform of Human L-type Ca2+Channel Is Up-regulated by Protein Kinase C

Blumenstein

Kanevsky

Sahar

et al. 2002

Journal of Biological Chemistry

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Human L-type voltage-dependent Ca2؉ channels (␣ 1C , or Ca v 1.2) are up-regulated by protein kinase C (PKC) in native tissues, but in heterologous systems this modulation is absent. In rat and rabbit, ␣ 1C has two N-terminal (NT) isoforms, long and short, with variable initial segments of 46 and 16 amino acids, respectively. The initial 46 amino acids of the long-NT ␣ 1C are crucial for PKC regulation. However, only a short-NT human ␣ 1C is known. We assumed that a long-NT isoform of human ␣ 1C may exist. By homology screening of human genomic DNA, we identified a stretch (termed exon 1a) highly homologous to rabbit long-NT, separated from the next known exon of ␣ 1C (exon 1b, which encodes the alternative, short-NT) by an ϳ80 kb-long intron. The predicted 46-amino acid protein sequence is highly homologous to rabbit long-NT. Reverse transcriptase PCR showed the presence of exon 1a transcript in human cardiac RNA. Expression of human long-NT ␣ 1C in Xenopus oocytes produced Ca 2؉ channel enhanced by a PKC activator, whereas the short-NT ␣ 1C was inhibited. The long-NT isoform may be the Ca 2؉ channel enhanced by PKCactivating transmitters in human tissues.Voltage-dependent L-type Ca 2ϩ channels are crucial for cardiac and smooth muscle contraction and hormone secretion, and they regulate gene expression in the brain (1-3). Their function is highly regulated by hormones and neurotransmitters, largely via activation of protein kinases (3,4). Regulation by PKC 1 is believed to be of substantial physiological importance, mediating all or part of the effects of several hormones and intracellular messengers (4). PKC enhances L-type Ca 2ϩ currents in diverse human tissues and cell lines: heart, neuroblastoma, T-cells, and endocrine cells (5-10). Dual modulation by PKC is often observed with activation followed by, or concomitant with, inhibition (5, 10). Similar enhancement by PKC, sometimes followed by inhibition, has been described in other mammals (11,12) and was reproduced in Xenopus oocytes expressing the cloned rabbit cardiac L-type Ca 2ϩ channels (13,14). However, expression of human L-type channels, encoded by all cDNA cloned to date, yielded Ca 2ϩ channels that were only inhibited by PKC; the enhancement could not be reconstituted (15). The reason for the inability to reproduce the PKC modulation of human L-type channels remained unknown. The main, pore-forming subunit of cardiac/smooth muscle L-type channel (␣ 1C or Ca v 1.2), also present in the brain, is the product of the ␣ 1C gene, CACNA1C (16). Several splice variants of CACNA1C are known (17,18). The resulting isoforms of human ␣ 1C protein show differential distribution in human tissues, and in failing versus normal myocardium. They play important roles in Ca 2ϩ -dependent inactivation, oxygen sensing, and drug sensitivity (18 -22). However, the genomic structure of the beginning of N-terminal region of human ␣ 1C is not entirely clear. In the two best studied mammalian species, rat and rabbit, two N-terminal isoforms of ␣ 1C cDNA are known, which mos...

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“…100 Más aún, el sistema dopaminérgico hipotalámico tiene una actividad reducida en un modelo de rata autista, 101 que permite explicar las modificaciones en la concentración de prolactina sistémica de niños primordialmente medicados. 102,103 Cerebelo. El cerebelo es una estructura que muestra una alteración significativa en las personas con autismo (Fig.…”

Section: Circunferencia De La Cabeza Y Volumenunclassified

Un segundo espectro del autismo: de la conducta a la neurona

Manzo

2019

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El trastorno del espectro autista es una alteración del desarrollo neural que se refleja en modificaciones significativas de la conducta infantil. En la versión más reciente del Manual Diagnóstico y Estadístico de Trastornos Mentales, se describe al autismo como un conjunto de modificaciones de la conducta que incluyen decremento en la interacción social, decremento en las habilidades de comunicación verbal o respuestas inapropiadas durante la conversación, manifestaciones de conductas repetitivas o estereotipadas, carencia de empatía para entablar relaciones afectivas y obsesiones inapropiadas sobre objetos específicos. Todo esto acompañado de una habilidad cognitiva que va desde altos niveles de inteligencia hasta alteraciones intelectuales severas. Por ello, ahora se reconoce al autismo como un abanico de conductas agrupadas bajo el concepto de Trastorno del Espectro Autista. Sin embargo, hay otros espectros, como aquel que está directamente relacionado con las bases neurales. En esta revisión se describen las diferentes metodologías para diagnosticar conductualmente al autismo, las comorbilidades que se presentan, las regiones del sistema nervioso central afectadas, y el papel que juegan las neuronas espejo y la glía; con ello se percibe que la etiología del autismo puede presentarse en alguna de estas regiones. A pesar de que los temas no son exhaustivos, tienen el propósito de proponer que el Trastorno del Espectro Autista, que se basa en la conducta, tiene un segundo espectro: aquel que va de la conducta a la neurona.

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Potentiation of Prolactin Secretion following Lactotrope Escape from Dopamine Action

Cited by 10 publications

References 82 publications

Potentiation of Prolactin Secretion following Lactotrope Escape from Dopamine Action

Potentiation of Prolactin Secretion following Lactotrope Escape from Dopamine Action

A Novel Long N-terminal Isoform of Human L-type Ca2+Channel Is Up-regulated by Protein Kinase C

Un segundo espectro del autismo: de la conducta a la neurona

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