Endothelin-B receptors activate Gai3

Kenichiro Kitamura, Naoki Shiraishi, William D. Singer, Mary E. Handlogten, Kimio Tomita, R. Tyler Miller

Research output: Contribution to journalArticlepeer-review


Endo-thelin (ET) receptors activate heterotrimeric G proteins that are members of the Gi; Gq, and Gs families but may also activate members of other families such as 60112/13. Gotis has multiple complex cellular effects that are similar to those of ET. We studied the ability of ET receptors to activate Gais using an assay for G protein a-chain activation that is based on the fact that an activated (GTP-bound) a-chain is resistant to trypsinization compared with an inactive (GDP-bound) a-chain. Nonhydrolyzable guanine nucleotides and AlMgF protected Ga13 from degradation by trypsin. In membranes from human embryonic kidney 293 cells that coexpress ETβ receptors and ai3, ET-3 and 5'-guanylylimidodiphosphate [Gpp(NH)p] increased the protection of 013 compared with Gpp(NH)p alone. The specificity of ETβ receptor-aja coupling was documented by showing that β2 receptors and isoproterenol or ETA receptors and ET-1 did not activate aïs and that a specific antagonist for ETβ receptors blocked ET-3-dependent activation of ai3. Copyright a> 1999 the American Physiological Society.

Original languageEnglish (US)
JournalAmerican Journal of Physiology
Issue number4 PART 1
StatePublished - 1999


  • Cell signaling
  • G protein
  • G protein-coupled receptor

ASJC Scopus subject areas

  • Physiology (medical)


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