Angiotensin II AT1 receptor stimulates Na+-K+ATPase activity through a pathway involving PKC-ζ in rat thyroid cells

S. Marsigliante, A. Muscella, M. G. Elia, S. Greco, C. Storelli

Research output: Contribution to journalArticlepeer-review


Angiotensin II (Ang II) receptor subtype 1, AT1, is expressed by the rat thyroid. A relationship between thyroid function and several components of the renin-angiotensin system has also been established, but the Ang II cellular effects in thyrocytes and its transduction signalling remain undefined. The aim of the present paper was to investigate the modulation of the activity of the Na+-K+ATPase by Ang II and its intracellular transduction pathway in PC-Cl3 cells, an established epithelial cell line derived from rat thyroid. Here we have demonstrated, by RT-PCR analysis, the expression of mRNA for the Ang II AT1 receptor in PC-Cl3 cells; mRNA for the Ang II AT2 receptor was not detected. Ang II was not able to affect the intracellular Ca2+ concentration in fura-2-loaded cells, but it stimulated the translocation from the cytosol to the plasma membrane of atypical protein kinase C-zeta (PKC-ζ) and -iota (PKC-ι) isoforms with subsequent phosphorylation of the extracellular signal-regulated kinases 1 and 2 (ERK1 and 2). Translocated atypical PKCs displayed temporally different activations, the activation of PKC-ζ being the fastest. PC-Cl3 cells stimulated with increasing Ang II concentrations showed dose- and time-dependent activation of the Na+-K+ATPase activity, which paralleled the PKC-ζ translocation time course. Na+-K+ATPase activity modulation was dependent on PKC activation since the PKC antagonist staurosporine abolished the stimulatory effect of Ang II. The inhibition of the ERK kinases 1 and 2 (MEK1 and 2) by PD098059 (2′-amino-3′-methoxyflavone) failed to block the effect of Ang II on the Na+-K+ATPase activity. In conclusion, our results suggest that Ang II modulates Na+-K+ATPase activity in PC-Cl3 cells through the AT1 receptor via activation of atypical PKC-ζ while the Ang II-activated PKC-ι appears to have other as yet unknown function.

Original languageEnglish
Pages (from-to)461-470
Number of pages10
JournalJournal of Physiology
Issue number2
Publication statusPublished - Jan 15 2003

ASJC Scopus subject areas

  • Physiology


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