Sigma receptors are proteins found on mainly the surface of endoplasmic reticulum (ER) in certain cells. Sigma-1 and sigma-2 are the two main classes of these receptors. The sigma-1 receptor is involved neurological disorders and certain types of cancer. To understand better how the receptor is involved in disease and whether drugs developed to target it are working, it is important to be able to accurately trace the sigma-1 receptor. Researchers have developed a probe, which can identify and latch onto the sigma-1 receptor.
The research team had previously developed molecules with such binding potential. However, upon detailed analysis of the sigma-1 receptor structure, they realized that extending the length of these molecules would increase their binding affinity further. The team therefore created molecules with varying lengths and found one probe that bound to the receptor exceptionally well. For measuring and mapping the sigma receptors by nuclear imaging, radiolabeled iodine was introduced into the probe. The structure created subsequently bound to both sigma-1 and sigma-2 receptors.
Since sigma-1 and sigma-2 receptors are involved in prostate cancer, the team then tested the effects of their newly created molecular probe on prostate cancer cells. These cells have sigma receptors and thus any probe with a high affinity will attach to them and enter the cell. As expected, the probe signal from within the cell was high. When haloperidol--a drug specific to the sigma-1 receptor--was added to the mix this signal dropped, suggesting a competition between the two.
To finally assess the affinity of the probe for different tissues within the body, mice with prostatic tumors were used. While the probe easily entered and stayed within the tumors, its presence in the muscles and blood was less. The probe was thus highly specific for tissues with the presence of sigma receptors.
This study reports a sophisticated probe that binds to sigma-1 receptors better than previous probes developed. This coupled with its ability to escape non-specific tissues is a promising step forward in studying changes induced in the sigma-1 receptor in various disorders. The probe can also be used when developing drugs against the sigma-1 receptor to compare the binding affinities of such drugs. "These results provide useful information for developing sigma-1 receptor imaging probes", conclude the researchers.
https://www.kanazawa-u.ac.jp/latest-research/68344
https://www.sciencedirect.com/science/article/pii/S0968089618319989?via%3Dihub
Mapping and measuring proteins on the surfaces of endoplasmic reticulum (ER) in cells
- 1,593 views
- Added
Edited
Latest News
New origin of deep brain waves
By newseditor
Posted 17 Apr
Starving cells hijack prote…
By newseditor
Posted 17 Apr
Miniature battery-free epid…
By newseditor
Posted 17 Apr
Molecular causes of differe…
By newseditor
Posted 16 Apr
Cell's 'garbage disposal' h…
By newseditor
Posted 16 Apr
Other Top Stories
A key gene in the transmission of deadly sleeping sickness identified!
Read more
Biological wiring in bacteria never seen before!
Read more
Viral infection induces host mRNA to protect against antiviral resp…
Read more
New non-antibiotic strategy for the treatment of bacterial meningitis
Read more
A year in space has little effect on gut microbiome!
Read more
Protocols
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Modular dual-color BiAD sen…
By newseditor
Posted 31 Mar
Publications
The immunobiology of herpes…
By newseditor
Posted 17 Apr
Circulating microbiome DNA…
By newseditor
Posted 17 Apr
Spindle oscillations in com…
By newseditor
Posted 17 Apr
Oligodendroglial macroautop…
By newseditor
Posted 17 Apr
COPII with ALG2 and ESCRTs…
By newseditor
Posted 17 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar