Findings could yield potential new treatment to hypertension

 antibioticsAs our understanding of their targets becomes more sophisticated over the last few years, developing new drugs has become a lot more complicated.

A new study led by researchers in the labs of Terry Hébert and Stéphane Laporte at McGill University in Montreal, challenges our notion of what certain drugs do by examining the interactions between drugs targeting two different receptor molecules in vascular smooth muscle – both of which are important in the control of blood pressure and the development of hypertension, a common problem facing many Canadians. The findings were reported in the January 30th issue of the Journal of Biological Chemistry.

According to Statistics Canada, hypertension is prevalent in 22% of Canadian adults aged 20 to 79 years. However, 17% of those afflicted are unaware of their condition. The rate increases in line with age, with 52% of Canadians aged 60 to 79 diagnosed with hypertension by a health-care professional, taking hypertension medication, or have high measured blood pressure. Hypertension can result in heart attack and stroke, which are among the leading causes of hospitalization and death in Canada and responsible for one in three deaths worldwide, according to the U.S. Centers for Disease Control and Prevention.

In the study, co-first authors Eugénie Goupil and Dany Fillion identified a novel interaction between prostaglandin F and angiotensin receptors which altered how each responds to molecules which activate or inhibit them. “The results are surprising because they challenge our notions of exactly what it is that these drugs do,” says Goupil. “Interestingly, because the two receptors interact, an impact on one receptor that is being targeted by a specific drug translates into changes in responses to the other receptor as well.”

“We also showed that the outcomes of combining drugs changes when we look in different cells or even at different signaling events within the same cells,” explains Dr. Hébert.  “This could change how we treat diseases like hypertension or heart failure as the effects of combining drugs might lead to new therapeutic approaches as we learn to target the larger “two receptor” or “heterodimer” complexes instead of each receptor alone.”

The researchers are now examining a wider variety of activators and inhibitors for each receptor to see how different combinations of drugs might translate into more effective ways to control how the receptors work in health and in disease, something that the pharmaceutical companies generally do not screen for.

The research was supported by the Canadian Institutes for Health Research.

“Angiotensin II Type I and Prostaglandin F2α Receptors Cooperatively Modulate Signaling in Vascular Smooth Muscle Cells”  Eugénie Goupil, Dany Fillion, Stéphanie Clément, Xiaoyan Luo, Dominic Devost, Rory SlenoDarlaine Pétrin, H. Uri Saragovi, Éric Thorin, Stéphane A. Laporte, and Terence E. Hébert. Journal of Biological Chemistry. 2015 90(5):3137-48
 More from the lab of Dr. Hébert 
More from the lab of Dr. Laporte 

March 26, 2015