Nav: Home

Researchers find new role for dopamine in gene transcription and cell proliferation

November 14, 2019

WASHINGTON (Nov. 14, 2019) - The dopamine D2 receptor has a previously unobserved role in modulating Wnt expression and control of cell proliferation, according to a new study from the George Washington University (GW) and the University of Pittsburgh. The research, published in Scientific Reports, could have implications for the development of new therapeutics across multiple disciplines including nephrology, endocrinology, and psychiatry.

Dopamine is traditionally studied in the central nervous system, however, it is increasingly implicated in regulating functions of various other organs. This new study identifies a new role for dopamine signaling via the D2 receptor outside the brain - in controlling signaling through the Wnt/β-catenin pathway, in part, through its effects on expression of Wnt3a, a key Wnt receptor ligand.

Both dopamine and the Wnt/β-catenin signaling pathways are ubiquitous across organ systems and species. Wnt signaling is essential for development and cell proliferation, and is associated with a number of diseases from cancer to schizophrenia. However, little is known about the underlying mechanism regulating expression of Wnt3a, or the modulation of its activity.

"In our research, we found that the dopamine D2 receptor is a transcriptional regulator of Wnt signaling and this ability to modulate Wnt signaling is important for better understanding development of hypertension," said Prasad Konkalmatt, PhD, assistant research professor of medicine at the GW School of Medicine and Health Sciences and a first author on the study.

The research team focused the study on signaling in the kidneys and in the pancreas. More broadly, the study shows that dopamine receptors can act as regulators of gene transcription and that this signaling is important in controlling cell proliferation under healthy and disease conditions.

These results were unexpected, surprising the investigators by how well conserved this dopamine regulation was across species and organs. This work also showed for the first time that lithium, one of the most commonly used psychiatric medications today, strongly increases the expression of D2 receptors, providing a new mechanism of action for this drug.

"Our work opens the door to a new way of thinking about dopamine signaling and its regulation," said Zachary Freyberg, MD, PhD, assistant professor of psychiatry and cell biology at the University of Pittsburgh School of Medicine and a senior author on the study. "By providing a new mechanism for the actions of lithium, we can better understand how this medication works and make better medications in the future to treat bipolar disorder and to improve the lives of the millions of people living with this illness."

The investigators also discovered that a number of common gene polymorphisms associated with hypertension and renal injury control D2 receptor expression in renal cells. This discovery provides new mechanisms and drug discovery targets for hypertension and renal injury.

"Our findings have broad implications in terms of how we think about dopamine receptor signaling, especially given that the receptors are targets for diabetes and potentially for hypertension and renal injury," explained Ines Armando, PhD, associate research professor of medicine at the GW School of Medicine and Health Sciences and a senior author on the study. "Expanding our understanding of this unique signaling specific to individual patients offers the promise of more effective precision medicine."
-end-
This research was funded by grants from the National Institutes of Health, the U.S. Department of Defense, and the John F. and Nancy A. Emmerling Fund of The Pittsburgh Foundation.

The study, titled "Dopamine D2 Receptor Modulates Wnt Expression and Control of Cell Proliferation," is published in Scientific Reports and can be found at http://www.nature.com/articles/s41598-019-52528-4.

George Washington University

Related Hypertension Articles:

Overactive enzyme causes hereditary hypertension
After more than 40 years, several teams at the MDC and ECRC have now made a breakthrough discovery with the help of two animal models: they have proven that an altered gene encoding the enzyme PDE3A causes an inherited form of high blood pressure.
Diagnosing hypertension in children
Study results call into question the utility of testing blood pressure load--the proportion of elevated blood pressure readings detected over 24 hours--for diagnosing hypertension in children.
When the best treatment for hypertension is to wait
A new study concluded that a physician's decision not to intensify hypertension treatment is often a contextually appropriate choice.
Treatment of hypertension induced albuminuria
Patients with albuminuria will usually need more than one drug to achieve blood pressure control, particularly if the aim is also to reduce albuminuria.
Diagnosing and treating resistant hypertension
Resistant blood pressure affects 12 percent to 15 percent of people currently being treated for high blood pressure.
Dementia can be caused by hypertension
A new study in Cardiovascular Research indicates that patients with high blood pressure are at a higher risk of developing dementia.
Hormone imbalance causes treatment-resistant hypertension
British researchers have discovered a hormone imbalance that explains why it is very difficult to control blood pressure in around 10 per cent of hypertension patients.
Breastfeeding reduces hypertension risk
A study published in the American Journal of Hypertension indicates that women who breastfeed more children, and for longer periods of time, are less likely to suffer from hypertension after they reach menopause.
Lung cancer triggers pulmonary hypertension
Nearly half of all advanced-stage lung cancer patients develop arterial pulmonary hypertension.
Targeting mitochondria in pulmonary hypertension
Investigators at the University of Alberta and the Imperial College of Medicine have shown that the generic drug, Dichloroacetate (DCA), can decrease the blood pressure in the lungs of pulmonary arterial hypertension patients and improve their ability to walk, without significant side effects at the doses tested.
More Hypertension News and Hypertension Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: The Power Of Spaces
How do spaces shape the human experience? In what ways do our rooms, homes, and buildings give us meaning and purpose? This hour, TED speakers explore the power of the spaces we make and inhabit. Guests include architect Michael Murphy, musician David Byrne, artist Es Devlin, and architect Siamak Hariri.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at Radiolab.org/donate.     You can read The Transition Integrity Project's report here.