Scientists have uncovered how an important regulator for blood pressure works in the human body using a sophisticated X-ray analysis and they believe that the findings could lead to new blood pressure drugs with fewer side effects.
The findings could fast-track the development of new medications with fewer side-effects, noted Professor Vadim Cherezov, lead researcher at the University of Southern California Dornsife College of Letters, Arts and Sciences.
The X-ray analysis revealed the molecular structure of the angiotensin receptor AT1R.
"Despite its medical relevance, the structure of this receptor was unknown up to now," said study co-author Cornelius Gati from the Center for Free-Electron Laser Science at Deutsches Elektronen-Synchrotron (DESY) in Germany.
Angiotensin receptor AT1R, when activated by the hormone angiotensin, triggers two major signalling pathways inside cells.
One of them, mediated by G proteins (a family of proteins that act as switches and transmit signals through cell walls), causes the constriction of blood vessels leading to an increase in blood pressure. Another pathway, mediated by arrestin, confers a number of beneficial effects.
Doctors regularly prescribe drugs, known as angiotensin receptor blockers, that turn off both pathways, which prevents the constriction but also has side effects, such as dizziness, headache, drowsiness, and elevated levels of potassium in the blood.
"It is like using a two-by-four to kill a fly. Yes, it works - but perhaps a more refined approach could achieve the positive results without many side effects by only blocking the G protein pathway, while keeping the arresting pathway active," Cherezov said.