Calcium as an inflammatory stimulus

Scientists at Leipzig University have discovered that calcium drives inflammation. Their specialist publication in "nature communications" describes the triggering stimulus through freely soluble calcium ions and the molecular pathway via special receptors. The work has implications for several medical fields and opens up new pharmacological approaches.

Calcium, which is important for numerous processes in the body, becomes an inflammatory stimulus when it accumulates in the space around the cells. This extracellular calcium activates what is known as the inflammasome, a large protein complex that is a key component of the body's immune system because it controls inflammatory reactions. The Leipzig working group led by Prof Ulf Wagner and Dr Manuela Rossol, rheumatologists at the University of Leipzig, has now been able to describe the upper end of the molecular pathway that calcium activates the mechanism: The inflammatory pathway is triggered via two receptors that recognise calcium.

GPRC6A receptor

One is the classic calcium receptor that has been known for a long time and is located in the parathyroid gland. This is where the calcium level is measured and monitored. Even a slight deviation in the calcium level causes problems and systemic effects on the organism. As a result, it immediately counter-regulates, which is why it is almost impossible to intervene therapeutically at this sensitive system site.

The second (G protein-coupled) receptor with the scientific name "GPRC6A" is a new discovery in connection with inflammation. It is not present on every cell, but definitely on the macrophages (monocytes) circulating in the blood. According to the researchers, this receptor is more important in a local inflammatory reaction, so that it can be inhibited without immediately upsetting the entire systemic calcium balance. This opens up therapeutic approaches, says Ulf Wagner: "Our medium-term goal, together with our pharmacologist, Prof Michael Schaefer, is to search for and develop inhibitors for this receptor."

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Link to the specialist publication in nature communications: http://www.nature.com/ncomms/journal/v3/n12/full/ncomms2339.html

Source: Press release of the University of Leipzig, number: 2013/097 from 11 April 2013