Studies Suggesting the Participation of Protein Kinase A in 1,25(OH)2-Vitamin D3-Dependent Protein Phosphorylation in Cardiac Muscle

We have previously established that the secosteroid hormone 1α,25-dihydroxy-vitamin D3[1,25(OH)2D3] rapidly stimulates dihydropyridine-sensitive calcium channel-mediated Ca2+influx in chick cardiac muscle by a non-genomic action which is accompanied by phosphorylation of microsomal proteins. In the...

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Veröffentlicht in:Journal of molecular and cellular cardiology 1998-02, Vol.30 (2), p.225-233
Hauptverfasser: Santillán, Graciela E., Boland, Ricardo L.
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Sprache:eng
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Zusammenfassung:We have previously established that the secosteroid hormone 1α,25-dihydroxy-vitamin D3[1,25(OH)2D3] rapidly stimulates dihydropyridine-sensitive calcium channel-mediated Ca2+influx in chick cardiac muscle by a non-genomic action which is accompanied by phosphorylation of microsomal proteins. In the present study, we investigated the participation of the cyclic AMP/protein kinase A (PKA) signalling pathway in hormone-induced changes on protein phosphorylation in chick heart tissue. A major increase in the phosphorylation of a microsomal protein of 45 kDa, and, to a lesser extent, of a protein of 70 kDa, was observed after incubation with [γ-32P]ATP of membranes isolated from heart thin slices (HTS) pretreated for 1–5 min with 1,25(OH)2D3. This effect was dose- and time-dependent, reaching a maximum after 3 min and at the physiological concentrations of 10−10and 10−11M. 1,25(OH)2D3steadily increased cellular cAMP levels as a function of the dose (10−12–10−9M). The specific agonist of PKA, Sp-cAMPS and the PKA catalytic subunit stimulated the phosphorylation of the same membrane proteins as the hormone. The 1α,25-dihydroxy-vitamin D3-dependent changes in microsomal protein phosphorylation were diminished by the specific PKA inhibitor, Rp-cAMPS. In addition, the PKA activity ratio (−cAMP/+cAMP) increased 60% above the control after treatment of HTS with 10−11M1,25(OH)2D3. The data obtained clearly indicate that activation of the cAMP/PKA signalling pathway mediates the stimulation of protein phosphorylation by 1α,25-dihydroxy-vitamin D3in chick cardiac muscle.
ISSN:0022-2828
1095-8584
DOI:10.1006/jmcc.1997.0577