Endothelin-B receptors activate Galpha 13

Endothelin (ET) receptors activate heterotrimeric G proteinsthat are members of the G_i,G_q, andG_s families but may also activatemembers of other families such asG_12/13.G₁₃ has multiple complexcellular effects that are similar to those of ET. We studied theability of ET receptors to activateG₁₃ using an assay for Gprotein -chain activation that is based on the fact that an activated (GTP-bound) -chain is resistant to trypsinization compared with an inactive (GDP-bound) -chain. Nonhydrolyzable guanine nucleotides and AlMgF protectedG₁₃ from degradation bytrypsin. In membranes from human embryonic kidney 293 cells thatcoexpress ET_B receptors and₁₃, ET-3 and5'-guanylylimidodiphosphate [Gpp(NH)p] increased theprotection of ₁₃ compared withGpp(NH)p alone. The specificity ofET_Breceptor-₁₃ coupling wasdocumented by showing that ₂receptors and isoproterenol or ET_Areceptors and ET-1 did not activate₁₃ and that a specificantagonist for ET_B receptorsblocked ET-3-dependent activation of₁₃.