Endothelin ET a receptor regulates signaling and ANF gene expression via multiple G protein-linked pathways

Randa Hilal-Dandan, M. Teresa Ramirez, Sonia Villegas, Annette Gonzalez, Yuka Endo-Mochizuki, Joan Heller Brown, Laurence L. Brunton*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

We have char-acterized the interaction of endothelin (ET) with cultured neonatal rat ventricular myocytes. Binding studies indicate a single population of ETA receptors [53, 000 sites/cell, apparent dissociation constant (K d ) for ET-1 ≈ 0.07 nM]. Analysis of mRNA levels for ET receptors using 35 cycles of reverse transcriptase-polymerase chain reaction demonstrates the presence of only ET A -receptor message. Studies with ET-1 and a variety of congeners and antagonists indicate that ETA receptors couple to both the stimulation of phosphoinositide turnover and the inhibition of adenylyl cyclase. In myocytes transfected with an atrial natriuretic factor (ANF) promoter linked to a luciferase reporter gene, ET-1 stimulates luciferase expression through an ET A receptor. These data indicate that the ET A receptor is the exclusive receptor on neonatal ventricular myocytes and that this receptor couples to both phosphoinositide hydrolysis and adenylyl cyclase. ET-1 also induces a threefold increase in mitogen-activated protein kinase (MAPK) activity, an effect that is not sensitive to pertussis toxin (PTx). By contrast, ET-stimulated ANFluciferase expression is partially inhibited by treatment of cells with PTx, suggesting that both PTx-sensitive (G i ) and PTx-insensitive (G q ) pathways mediate the effects of ET-1 on ANF gene expression in neonatal myocytes and that hormonal regulation of ANF expression may utilize pathways in addition to the activation of MAPK. neonatal ventricular myocytes; phospholipase C; adenylyl cyclase; hypertrophy

Original languageEnglish (US)
JournalAmerican Journal of Physiology
Volume272
Issue number1 PART 2
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Physiology (medical)

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