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Paliperidone and aripiprazole differentially affect the strength of calcium-secretion coupling in female pituitary lactotrophs
Hyperprolactinemia is a common adverse in vivo effect of antipsychotic medications that are used in the treatment of patients with schizophrenia. Here, we compared the effects of two atypical antipsychotics, paliperidone and aripiprazole, on cAMP/calcium signaling and prolactin release in female rat...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4894395/ https://www.ncbi.nlm.nih.gov/pubmed/25754735 http://dx.doi.org/10.1038/srep08902 |
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author | Kucka, Marek Tomić, Melanija Bjelobaba, Ivana Stojilkovic, Stanko S. Budimirovic, Dejan B. |
author_facet | Kucka, Marek Tomić, Melanija Bjelobaba, Ivana Stojilkovic, Stanko S. Budimirovic, Dejan B. |
author_sort | Kucka, Marek |
collection | PubMed |
description | Hyperprolactinemia is a common adverse in vivo effect of antipsychotic medications that are used in the treatment of patients with schizophrenia. Here, we compared the effects of two atypical antipsychotics, paliperidone and aripiprazole, on cAMP/calcium signaling and prolactin release in female rat pituitary lactotrophs in vitro. Dopamine inhibited spontaneous cAMP/calcium signaling and prolactin release. In the presence of dopamine, paliperidone rescued cAMP/calcium signaling and prolactin release in a concentration-dependent manner, whereas aripiprazole was only partially effective. In the absence of dopamine, paliperidone stimulated cAMP/calcium signaling and prolactin release, whereas aripiprazole inhibited signaling and secretion more potently but less effectively than dopamine. Forskolin-stimulated cAMP production was facilitated by paliperidone and inhibited by aripiprazole, although the latter was not as effective as dopamine. None of the compounds affected prolactin transcript activity, intracellular prolactin accumulation, or growth hormone secretion. These data indicate that paliperidone has dual hyperprolactinemic actions in lactotrophs i) by preserving the coupling of spontaneous electrical activity and prolactin secretion in the presence of dopamine and ii) by inhibiting intrinsic dopamine receptor activity in the absence of dopamine, leading to enhanced calcium signaling and secretion. In contrast, aripiprazole acts on prolactin secretion by attenuating, but not abolishing, calcium-secretion coupling. |
format | Online Article Text |
id | pubmed-4894395 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-48943952016-06-10 Paliperidone and aripiprazole differentially affect the strength of calcium-secretion coupling in female pituitary lactotrophs Kucka, Marek Tomić, Melanija Bjelobaba, Ivana Stojilkovic, Stanko S. Budimirovic, Dejan B. Sci Rep Article Hyperprolactinemia is a common adverse in vivo effect of antipsychotic medications that are used in the treatment of patients with schizophrenia. Here, we compared the effects of two atypical antipsychotics, paliperidone and aripiprazole, on cAMP/calcium signaling and prolactin release in female rat pituitary lactotrophs in vitro. Dopamine inhibited spontaneous cAMP/calcium signaling and prolactin release. In the presence of dopamine, paliperidone rescued cAMP/calcium signaling and prolactin release in a concentration-dependent manner, whereas aripiprazole was only partially effective. In the absence of dopamine, paliperidone stimulated cAMP/calcium signaling and prolactin release, whereas aripiprazole inhibited signaling and secretion more potently but less effectively than dopamine. Forskolin-stimulated cAMP production was facilitated by paliperidone and inhibited by aripiprazole, although the latter was not as effective as dopamine. None of the compounds affected prolactin transcript activity, intracellular prolactin accumulation, or growth hormone secretion. These data indicate that paliperidone has dual hyperprolactinemic actions in lactotrophs i) by preserving the coupling of spontaneous electrical activity and prolactin secretion in the presence of dopamine and ii) by inhibiting intrinsic dopamine receptor activity in the absence of dopamine, leading to enhanced calcium signaling and secretion. In contrast, aripiprazole acts on prolactin secretion by attenuating, but not abolishing, calcium-secretion coupling. Nature Publishing Group 2015-03-10 /pmc/articles/PMC4894395/ /pubmed/25754735 http://dx.doi.org/10.1038/srep08902 Text en Copyright © 2015, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Kucka, Marek Tomić, Melanija Bjelobaba, Ivana Stojilkovic, Stanko S. Budimirovic, Dejan B. Paliperidone and aripiprazole differentially affect the strength of calcium-secretion coupling in female pituitary lactotrophs |
title | Paliperidone and aripiprazole differentially affect the strength of calcium-secretion coupling in female pituitary lactotrophs |
title_full | Paliperidone and aripiprazole differentially affect the strength of calcium-secretion coupling in female pituitary lactotrophs |
title_fullStr | Paliperidone and aripiprazole differentially affect the strength of calcium-secretion coupling in female pituitary lactotrophs |
title_full_unstemmed | Paliperidone and aripiprazole differentially affect the strength of calcium-secretion coupling in female pituitary lactotrophs |
title_short | Paliperidone and aripiprazole differentially affect the strength of calcium-secretion coupling in female pituitary lactotrophs |
title_sort | paliperidone and aripiprazole differentially affect the strength of calcium-secretion coupling in female pituitary lactotrophs |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4894395/ https://www.ncbi.nlm.nih.gov/pubmed/25754735 http://dx.doi.org/10.1038/srep08902 |
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