Endothelin-B receptors activate Gα₁₃

Endothelin (ET) receptors activate heterotrimeric G proteins that are members of the G(i), G(q), and G(s) families but may also activate members of other families such as Gα(12/13). Gα₁₃ has multiple complex cellular effects that are similar to those of ET. We studied the ability of ET receptors to activate Gα₁₃ using an assay for G protein α-chain activation that is based on the fact that an activated (GTP-bound) α-chain is resistant to trypsinization compared with an inactive (GDP-bound) α- chain. Nonhydrolyzable guanine nucleotides and AlMgF protected Gα₁₃ from degradation by trypsin. In membranes from human embryonic kidney 293 cells that coexpress ET(B) receptors and α₁₃, ET-3 and 5'- guanylylimidodiphosphate [Gpp(NH)p] increased the protection of α₁₃ compared with Gpp(NH)p alone. The specificity of ET(B) receptor-α₁₃ coupling was documented by showing that β₂ receptors and isoproterenol or ET(A) receptors and ET-1 did not activate α₁₃ and that a specific antagonist for ET(B) receptors blocked ET-3-dependent activation of α₁₃.