Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The pharmacological “fingerprint“ of the fourth opioid receptor

27.03.2019

Pharmacologists from Jena, Toulouse, St. Louis and Boca Raton as well as Montreal, Seattle and Mountain View were able to decipher the molecular behavior of the nociceptin receptor in cells and intact animals. Now published in Science Signaling, their research paper on the investigation of the fourth opioid receptor is an important prerequisite for development and clinical evaluation of new pain medications.

Also known as Orphanin FQ-receptor, the nociceptin receptor is the youngest member in the opioid receptor family. Receptors are large protein molecules located in the cell membrane of nerve cells that function as docking stations for external signal molecules and then transmit this information inside the cell.


Pharmacologist Dr. Anika Mann from Jena University Hospital studied the regulation of the fourth opioid receptor.

Picture: Katja Bornkessel/UKJ

In this way, they regulate important functions in the central nervous system, including pain perception, motivation or reward. All opioid receptors are targets for pain-alleviating drugs, that includes morphine binding to the most-studied µ-opioid receptor, as well as the closely related δ- and κ-opioid receptors and the nociceptin receptor that was first described 25 years ago.

Depending on the receptor type, drug effects are often followed by undesirable side-effects, ranging from respiratory depression, development of tolerance and dependence, to seizures, mood changes and dizziness.

The development and aggressive marketing of synthetic and highly-potent opioids targeting the µ-opioid receptor but which quickly lose their effectiveness after prolonged use, has led to the so-called “opioid epidemic” with an average 130 casualties per day in the USA alone. Scientists and pharmaceutical companies are therefore searching with urgency to find new and safer drugs for the treatment of severe pain. In their focus are now also the nearest relatives of the µ-opioid receptor.

Stefan Schulz, professor of pharmacology and toxicology at the University Jena Hospital, has worked for many years with his research team on the signaling properties of opioid receptors. One important step in this process is the attachment of phosphate groups to the receptor protein.

“This phosphorylation changes the shape and binding properties of the receptor and regulates therefore the receptor activity. Phosphorylation is most important for desensitization when the receptor is flooded by signaling molecules, eventually becomes insensitive and finally gets internalized into the cell”, explains Stefan Schulz.

In a research collaboration with scientists from the universities of Toulouse, St. Louis, Boca Raton, Montreal, Seattle and Mountain View and with support from the German Research Council within the Transregio “ReceptorLight”, Prof. Schulz’s research team now studied the activity of the nociceptin receptor and took its pharmacological “fingerprint”. The scientists studied the receptor phosphorylation after adding various natural and synthetic drugs. Their results were now published in the prestigious journal Science Signaling.

“By tagging with specific antibodies we could localize four different phosphorylation sites in cell culture and determine the temporal sequence in which they get phosphorylated. The various drugs differ in their efficiency how they can activate the receptor and trigger the phosphorylation”, summarizes first author Dr. Anika Mann the most important results.

These could also be verified in animal studies in genetically-engineered mice where a fluorescent molecule had been attached to the nociceptin receptor. In these mice, receptor activation was shown to be dependent on the dose and chemical class of the drugs.

The scientists are especially interested in new chemical compounds that activate both the µ-opioid and the nociceptin receptor. “We have evidence that the analgesic effect is stronger in such compounds, but with less side-effects in comparison to the classical opioids. More research in this direction is really important”, affirms Stefan Schulz. He is sure that his research team has made an important contribution to this goal by taking the pharmacological “fingerprint” of the nociceptin receptor.

Wissenschaftliche Ansprechpartner:

Prof. Dr. Stefan Schulz, Dr. Anika Mann
Institute of Pharmacology and Toxicology
University Hospital Jena
Tel.: +49 3641 9325651, +49 3641 9325671
e-Mail: stefan.schulz@med.uni-jena.de, Anika.Mann@med.uni-jena.de

Originalpublikation:

Mann A, et al. Agonist-selective NOP receptor phosphorylation correlates in vitro and in vivo and reveals differential post-activation signaling by chemically diverse agonists. Sci. Signal. 12, eaau8072 (2019). DOI: 10.1126/scisignal.aau8072

Dr. Uta von der Gönna | idw - Informationsdienst Wissenschaft
Further information:
http://www.uniklinikum-jena.de

More articles from Life Sciences:

nachricht New eDNA technology used to quickly assess coral reefs
18.04.2019 | University of Hawaii at Manoa

nachricht New automated biological-sample analysis systems to accelerate disease detection
18.04.2019 | Polytechnique Montréal

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

A stellar flare 10 times more powerful than anything seen on our sun has burst from an ultracool star almost the same size as Jupiter

  • Coolest and smallest star to produce a superflare found
  • Star is a tenth of the radius of our Sun
  • Researchers led by University of Warwick could only see...

Im Focus: Quantum simulation more stable than expected

A localization phenomenon boosts the accuracy of solving quantum many-body problems with quantum computers which are otherwise challenging for conventional computers. This brings such digital quantum simulation within reach on quantum devices available today.

Quantum computers promise to solve certain computational problems exponentially faster than any classical machine. “A particularly promising application is the...

Im Focus: Largest, fastest array of microscopic 'traffic cops' for optical communications

The technology could revolutionize how information travels through data centers and artificial intelligence networks

Engineers at the University of California, Berkeley have built a new photonic switch that can control the direction of light passing through optical fibers...

Im Focus: A long-distance relationship in femtoseconds

Physicists observe how electron-hole pairs drift apart at ultrafast speed, but still remain strongly bound.

Modern electronics relies on ultrafast charge motion on ever shorter length scales. Physicists from Regensburg and Gothenburg have now succeeded in resolving a...

Im Focus: Researchers 3D print metamaterials with novel optical properties

Engineers create novel optical devices, including a moth eye-inspired omnidirectional microwave antenna

A team of engineers at Tufts University has developed a series of 3D printed metamaterials with unique microwave or optical properties that go beyond what is...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

Fraunhofer FHR at the IEEE Radar Conference 2019 in Boston, USA

09.04.2019 | Event News

 
Latest News

New automated biological-sample analysis systems to accelerate disease detection

18.04.2019 | Life Sciences

Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

18.04.2019 | Physics and Astronomy

New eDNA technology used to quickly assess coral reefs

18.04.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>