Endothelin-B receptors activate G alpha(13)

Endothelin (ET) receptors activate heterotrimeric G proteins that are membe rs of the G(i), G(q), and G(s) families but may also activate members of ot her families such as G alpha(12/13). G alpha(13) has multiple complex cellu lar effects that are similar to those of ET. We studied the ability of ET r eceptors to activate G alpha(13) using an assay for G protein alpha-chain a ctivation that is based on the fact that an activated (GTP-bound) alpha-cha in is resistant to trypsinization compared with an inactive (GDP-bound) alp ha-chain. Nonhydrolyzable guanine nucleotides and AlMgF protected G alpha(1 3) from degradation by trypsin. In membranes from human embryonic kidney 29 3 cells that coexpress ETB receptors and alpha(13), ET-3 and 5'-guanylylimi dodiphosphate [Gpp(NH)p] increased the protection of alpha(13) compared wit h Gpp(NH)p alone. The specificity of ETB receptor-alpha(13) coupling was do cumented by showing that beta(2) receptors and isoproterenol or ETA recepto rs and ET-1 did not activate alpha(13) and that a specific antagonist for E TB receptors blocked ET-3-dependent activation of alpha(13).