A consensus sequence in the endothelin-B receptor second intracellular loop is required for NHE3 activation by endothelin-1

Kamel Laghmani, Aiji Sakamoto, Masashi Yanagisawa, Patricia A. Preisig, Robert J. Alpern

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Endothelin-1 (ET-1) increases the activity of Na+/H+ exchanger 3 (NHE3), the major proximal tubule apical membrane Na +/H+ antiporter. This effect is seen in opossum kidney (OKP) cells expressing the endothelin-B (ETB) and not in cells expressing the endothelin-A (ETA) receptor. However, ET-1 causes similar patterns of protein tyrosine phosphorylation, adenylyl cyclase inhibition, and increases in cell [Ca2+] in ETA- and ET B-expressing OKP cells, implying that an additional mechanism is required for NHE3 stimulation by the ETB receptor. The present studies used ETA and ETB receptor chimeras and site-directed mutagenesis to identify the ET receptor domains that mediate ET-1 regulation of NHE3 activity. We found that binding of ET-1 to the ETA receptor inhibits NHE3 activity, an effect for which the COOH-terminal tail is necessary and sufficient. ET-1 stimulation of NHE3 activity requires the COOH-terminal tail and the second intracellular loop of the ETB receptor. Within the second intracellular loop, a consensus sequence was identified, KXXXVPKXXXV, that is required for ET-1 stimulation of NHE3 activity. This sequence suggests binding of a homodimeric protein that mediates NHE3 stimulation.

Original languageEnglish (US)
Pages (from-to)F732-F739
JournalAmerican Journal of Physiology - Renal Physiology
Volume288
Issue number4 57-4
DOIs
StatePublished - Apr 1 2005

Keywords

  • Endothelin-A/endothelin-B chimeras
  • Opossum kidney cells
  • Sodium/hydrogen antiporter activity

ASJC Scopus subject areas

  • Physiology
  • Urology

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