Single Receptor PAR1 Controls Opposing Responses in Blood Vessels

Researchers at the University of California San Diego have uncovered a critical mechanism in blood vessel function: a single protein, called protease-activated receptor-1 (PAR1), can trigger both inflammation and protective responses. This discovery, published in Cell Reports ¹, could lead to recent treatments for conditions like sepsis, heart attack and stroke.

The Dual Role of PAR1

PAR1, a cell-surface receptor, is essential for maintaining the structural integrity of blood vessels. Until recently, it was unclear how a single receptor could initiate such dramatically different outcomes – harmful inflammation and protective healing. The research team’s findings explain this molecular switch, offering potential therapeutic avenues for vascular inflammation and leakage.

How the Switch Works

PAR1 is activated when chemically cut by one of two enzymes. The opposing responses are orchestrated by the same intermediate enzyme, GRK5, but its location within the cell determines the outcome.

• Protective Response: When GRK5 is anchored to the cell’s plasma membrane, PAR1 triggers a protective response, counteracting inflammation.
• Harmful Response: When GRK5 acts from within the cytoplasm, PAR1 initiates an inflammatory response causing leakage.

models created with the AlphaFold 3 AI modeling tool revealed that different cuts to the outside portion of PAR1 dictate its behavior inside the cell ².

Implications for Future Therapies

“Our findings provide a detailed molecular explanation for how PAR1 can send such dramatically different messages depending on the activating enzyme,” said JoAnn Trejo, PhD, corresponding author and professor of pharmacology at UC San Diego School of Medicine ².

Co-corresponding author Irina Kufareva, PhD, professor at the UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences, added, “This opens the door to therapies that could harness the protective response of PAR1 without potentially triggering the opposite response” ².

Study Details

The study was published in Cell Reports on March 10, 2026, with a DOI of 10.1016/j.celrep.2026.117041 ¹.

Disclaimer: This article provides information for general knowledge and informational purposes only, and does not constitute medical advice. It is essential to consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.