Details

Autor(en) / Beteiligte

• Cuíñas, Andrea
• García-Morales, Verónica
• Viña, Dolores
• Gil-Longo, José
• Campos-Toimil, Manuel

Titel

Activation of PKA and Epac proteins by cyclic AMP depletes intracellular calcium stores and reduces calcium availability for vasoconstriction

Ist Teil von

• Life sciences (1973), 2016-06, Vol.155, p.102-109

Ort / Verlag

Netherlands: Elsevier Inc

Erscheinungsjahr

2016

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• We investigated the implication of PKA and Epac proteins in the endothelium-independent vasorelaxant effects of cyclic AMP (cAMP). Cytosolic Ca2+ concentration ([Ca2+]c) was measured by fura-2 imaging in rat aortic smooth muscle cells (RASMC). Contraction-relaxation experiments were performed in rat aortic rings deprived of endothelium. In extracellular Ca2+-free solution, cAMP-elevating agents induced an increase in [Ca2+]c in RASMC that was reproduced by PKA and Epac activation and reduced after depletion of intracellular Ca2+ reservoirs. Arginine-vasopressin (AVP)-evoked increase of [Ca2+]c and store-operated Ca2+ entry (SOCE) were inhibited by cAMP-elevating agents, PKA or Epac activation in these cells. In aortic rings, the contractions induced by phenylephrine in absence of extracellular Ca2+ were inhibited by cAMP-elevating agents, PKA or Epac activation. In these conditions, reintroduction of Ca2+ induced a contraction that was inhibited by cAMP-elevating agents, an effect reduced by PKA inhibition and reproduced by PKA or Epac activators. Our results suggest that increased cAMP depletes intracellular, thapsigargin-sensitive Ca2+ stores through activation of PKA and Epac in RASMC, thus reducing the amount of Ca2+ released by IP3-generating agonists during the contraction of rat aorta. cAMP rise also inhibits the contraction induced by depletion of intracellular Ca2+, an effect mediated by reduction of SOCE after PKA or Epac activation. Both effects participate in the cAMP-induced endothelium-independent vasorelaxation. [Display omitted]