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Eur J Pharmacol. 2013 Aug 15;714(1-3):202-9. doi: 10.1016/j.ejphar.2013.06.003. Epub 2013 Jun 19.

Stimulation of α₁-adrenoceptor or angiotensin type 1 receptor enhances DNA synthesis in human-induced pluripotent stem cells via Gq-coupled receptor-dependent signaling pathways.

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  • 1Department of Pharmacology, National Defense Medical College, Tokorozawa, Saitama, Japan.


Stimulation of either α₁-adrenoceptor or angiotensin type 1 receptor (AT₁ receptor) induces proliferation of mouse induced pluripotent stem (iPS) cells. Both α₁-adrenoceptor and AT₁ receptor are guanine nucleotide-binding protein q polypeptide (Gq)-coupled receptors. However, it is not fully understood whether stimulation of these Gq-coupled receptors exert a similar effect in human iPS cells, i.e. proliferation of human iPS cells. In this study, we evaluated the involvement of α₁-adrenoceptor and AT₁ receptor in the DNA synthesis of human iPS cells. Treatment with either l-phenylephrine (a selective α₁-adrenoceptor agonist) or angiotensin II (Ang II) significantly increased DNA synthesis in human iPS cells. Enhanced DNA synthesis was significantly inhibited by pretreatment with protein kinase C (PKC) inhibitors, mitogen-activated protein kinase kinase (MEK) inhibitor, or phosphatidylinositol-3 phosphate kinase (PI3K) inhibitor. Treatment with either l-phenylephrine or Ang II significantly increased Akt and p44/42 MAPK phosphorylation. Short interfering RNA (siRNA) directed against Gq significantly inhibited DNA synthesis and phosphorylation of Akt and p44/42 MAPK enhanced by l-phenylephrine or Ang II. These results suggest that stimulation of α₁-adrenoceptor or AT₁ receptor may enhance DNA synthesis in human iPS cells via Gq-coupled receptor-dependent signaling pathways.


Akt; Angiotensin type 1 receptor; Gq-coupled receptor; Induced pluripotent stem cell; Mitogen-activated protein kinase; α(1)-adrenoceptor

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