Landau Lab
Draft for review Prototype prepared for the Landau Lab · September 2026 · not yet final

Research/Theme 01

Dopamine signalling and GPR6

We study dopamine signalling and the role of the G protein-coupled receptor 6 (GPR6) in striatal function and behaviour.

Ongoing · 2025–2028StriatumParkinson's disease · depressionLundbeck Foundation · AUFF
Schematic of GPR6: a receptor with seven segments crossing the cell membrane, coupled on the inside to a Gs protein that raises cAMP. Gs cAMP ↑ GPR6 ACTIVE WITHOUTA KNOWN LIGAND OUTSIDE THE CELL INSIDE NC

01 Why GPR6

A receptor found where dopamine acts

GPR6 is an orphan receptor: its natural activating molecule is unknown. Unusually, it is active even without one, and it raises the level of the messenger molecule cAMP inside the cell.

GPR6 is concentrated in the striatum, in the "indirect pathway" neurons that carry dopamine D2 receptors — in rodents and in the human brain.

In these neurons, dopamine acting on D2 receptors lowers cAMP, while GPR6 pushes it up. Drugs that turn down GPR6's built-in activity — inverse agonists — are therefore expected to lower cAMP in these cells.

That makes GPR6 a possible way to act on a dopamine-regulated pathway without targeting dopamine receptors directly — relevant to Parkinson's disease and depression, the two main disease areas of our group.

Two dials on one neuron · indirect-pathway neuron, striatumSchematic
Dopamine D2 receptors lower cAMP; GPR6 raises it A neuron contains two receptors. On the left, dopamine binds the D2 receptor, which acts through Gi to lower cAMP. On the right, GPR6 is active on its own and acts through Gs to raise cAMP. A gauge in the middle shows the cAMP level. Adding an inverse agonist turns down GPR6 activity and lowers the gauge. DOPAMINE D2 receptor ACTS VIA Gi/o LOWERS cAMP INVERSE AGONIST GPR6 ACTIVE ON ITS OWNACTS VIA Gs RAISES cAMP cAMP

Two influences pull in opposite directions: dopamine at D2 receptors lowers cAMP, while GPR6 keeps pushing it up.

SourcesLobo et al., Nat Neurosci 2007 (doi:10.1038/nn1987); Oeckl et al., Exp Neurol 2014 (PubMed); Brice et al., J Pharmacol Exp Ther 2021 (doi:10.1124/jpet.120.000438); Brice et al., eClinicalMedicine 2024 (PMC). The diagram is a simplification of a stated drug rationale, not a measured result.

02 Two strands of work

Studying GPR6 now — and preparing to image it

Our GPR6 work runs along two connected lines. The first asks what GPR6 does, using approaches available today. The second builds the tools that would let us measure GPR6 directly — first in tissue, and eventually in the living brain.

Strand 1 · Current studies Ongoing

What does GPR6 do?Genetic and pharmacological studies

Genetic and pharmacological approaches are combined with PET, autoradiography and molecular analyses to investigate the effects of GPR6 modulation.

  • Genetic

    Changing GPR6 itself, to see which aspects of striatal function and behaviour depend on it.

  • Pharmacological

    Using CVN424, a drug that binds GPR6, to characterise the involvement of GPR6 in stress and depressive behaviour.

  • Read-outs
    PETAutoradiographyMolecular analysesBehaviour

This work is ongoing. Findings will be summarised here once they are published.

Strand 2 · Tool development Groundwork

Can we measure GPR6 binding?Tools for future GPR6 imaging

In parallel, we develop and validate tools to measure GPR6 binding and assess whether drugs engage the receptor, laying the groundwork for future imaging of GPR6 in the living brain.

  1. 1Measure GPR6 binding current focus

    Develop and validate tools that detect binding to GPR6.

  2. 2Show that a drug engages the receptor current focus

    Test whether, and how much, a drug occupies GPR6.

  3. 3Image GPR6 in the living brain future

    The longer-term aim these tools lay the groundwork for.

There is not yet an established PET tracer for imaging GPR6 in the living brain. So far, drug binding to GPR6 has been estimated from animal tissue and blood levels rather than measured directly in people.

Image to come

An approved image from our GPR6 work — with a full caption — can be placed here once it is ready to share.

How the methods fit togetherPET, autoradiography, tissue analyses and behaviour each answer different questions. See how they complement each other →

03 Funding and status

An ongoing project, 2025–2028

Lundbeck Foundation · Ascending Investigator

Exploring the role of GPR6 in developing new therapeutics for depression

Awarded 2024 · about DKK 6 million · project period 2025–2028

Announcement ↗
Aarhus University Research Foundation · AUFF Nova

G protein-coupled receptor 6: a potential biomarker and drug target for depression

Awarded 2025 · DKK 720,000

Announcement ↗

“We will use a newly developed drug that binds to this receptor, CVN424, to characterise the involvement of GPR6 in stress and depressive behaviour, providing evidence for the development of new treatments and diagnostic tools.”

Project summary · Lundbeck Foundation ↗

Results from this project have not yet been published. They will appear here, and in our publication list, as they are.

04 About CVN424

A research tool with a clinical history

  • CVN424 (solengepras) is an investigational, selective GPR6 inverse agonist developed by Cerevance.Brice et al. 2021 · Cerevance
  • Its clinical trials are in Parkinson's disease, including a Phase 3 trial. It is not an approved treatment.ClinicalTrials.gov
  • In our work, CVN424 is used as a research tool in preclinical models, to study the involvement of GPR6 in stress and depressive behaviour.Lundbeck Foundation project summary
MethodsFrom signal to evidenceHow PET, autoradiography, tissue analyses and behaviour complement each other.Read → LearnWhat can a PET scan tell us?An interactive walk-through with one tracer, [¹¹C]UCB-J.Try the tracer studio →