A β-Arrestin 2-Biased Dopamine Receptor Type 2 (DRD2) Agonist Is More Efficacious Than Cabergoline in Reducing Cell Proliferation in PRL-Secreting but Not in Non-Functioning Pituitary Tumor Cells Article Swipe
Genesio Di Muro
,
Federica Mangili
,
Emanuela Esposito
,
Anna Maria Barbieri
,
Rosa Catalano
,
Donatella Treppiedi
,
Giusy Marra
,
Emma Nozza
,
Andrea Lania
,
Emanuele Ferrante
,
Marco Locatelli
,
Maura Arosio
,
Erika Peverelli
,
Giovanna Mantovani
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3390/cancers15123218
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3390/cancers15123218
The molecular events underlying the variable effectiveness of dopamine receptor type 2 (DRD2) agonists in pituitary neuroendocrine tumors (PitNETs) are not known. Besides the canonical pathway induced by DRD2 coupling with Gi proteins, the β-arrestin 2 pathway contributes to DRD2′s antimitotic effects in PRL- and NF-PitNETs. A promising pharmacological strategy is the use of DRD2-biased agonists that selectively activate only one of these two pathways. The aim of the present study was to compare the effects of two biased DRD2 ligands, selectively activating the G protein (MLS1547) or β-arrestin 2 (UNC9994) pathway, with unbiased DRD2 agonist cabergoline in PRL- and NF-PitNET cells. In rat tumoral pituitary PRL-secreting MMQ cells, UNC9994 reduced cell proliferation with a greater efficacy compared to cabergoline (−40.2 ± 20.4% vs. −21 ± 10.9%, p < 0.05), whereas the G-protein-biased agonist induced only a slight reduction. β-arrestin 2 silencing, but not pertussis toxin treatment, reverted UNC9994 and cabergoline’s antiproliferative effects. In a cabergoline-resistant PRL-PitNET primary culture, UNC9994 inhibited cell proliferation and PRL release. In contrast, in NF-PitNET primary cultures (n = 23), biased agonists did not show better antiproliferative effects than cabergoline. In conclusion, the preferential activation of the β-arrestin 2 pathway by UNC9994 improves DRD2-mediated antiproliferative effects in PRL-PitNETs, suggesting a new pharmacological approach for resistant or poorly responsive tumors.
Related Topics
Concepts
Cabergoline
Agonist
Dopamine
Dopamine receptor D2
Receptor
Endocrinology
Dopamine agonist
Internal medicine
Dopamine receptor
Prolactinoma
Cancer research
Cell growth
Chemistry
Prolactin
Medicine
Biochemistry
Hormone
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/cancers15123218
- https://www.mdpi.com/2072-6694/15/12/3218/pdf?version=1686908813
- OA Status
- gold
- Cited By
- 3
- References
- 38
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4380987130
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4380987130Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3390/cancers15123218Digital Object Identifier
- Title
-
A β-Arrestin 2-Biased Dopamine Receptor Type 2 (DRD2) Agonist Is More Efficacious Than Cabergoline in Reducing Cell Proliferation in PRL-Secreting but Not in Non-Functioning Pituitary Tumor CellsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-06-16Full publication date if available
- Authors
-
Genesio Di Muro, Federica Mangili, Emanuela Esposito, Anna Maria Barbieri, Rosa Catalano, Donatella Treppiedi, Giusy Marra, Emma Nozza, Andrea Lania, Emanuele Ferrante, Marco Locatelli, Maura Arosio, Erika Peverelli, Giovanna MantovaniList of authors in order
- Landing page
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https://doi.org/10.3390/cancers15123218Publisher landing page
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https://www.mdpi.com/2072-6694/15/12/3218/pdf?version=1686908813Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.mdpi.com/2072-6694/15/12/3218/pdf?version=1686908813Direct OA link when available
- Concepts
-
Cabergoline, Agonist, Dopamine, Dopamine receptor D2, Receptor, Endocrinology, Dopamine agonist, Internal medicine, Dopamine receptor, Prolactinoma, Cancer research, Cell growth, Chemistry, Prolactin, Medicine, Biochemistry, HormoneTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
3Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 2, 2024: 1Per-year citation counts (last 5 years)
- References (count)
-
38Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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