AT(1)-receptor heterodimers show enhanced G-protein activation and alteredreceptor sequestration

The vasopressor angiotensin II regulates vascular contractility and blood p ressure through binding to type 1 angiotensin II receptors (AT(1); refs 1, 2). Bradykinin, a vasodepressor, is a functional antagonist of angiotensin II (ref. 3). The two hormone systems are interconnected by the angiotensin- converting enzyme, which releases angiotensin II from its precursor and ina ctivates the vasodepressor bradykinin(4). Here we show that the AT(1) recep tor and the bradykinin (B-2) receptor also communicate directly with each o ther. They form stable heterodimers, causing increased activation of G alph a(q) and G alpha(i) proteins, the two major signalling proteins triggered b y AT(1). Furthermore, the endocytotic pathway of both receptors changed wit h heterodimerization. This is the first example of signal enhancement trigg ered by heterodimerization of two different vasoactive hormone receptors.