{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:21:34Z","timestamp":1791336094280,"version":"4.3.1"},"reference-count":41,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2010,2]]},"abstract":"<jats:p> cAMP and Ca<jats:sup>2+<\/jats:sup> are antagonistic intracellular messengers for the regulation of vascular smooth muscle tone; rising levels of Ca<jats:sup>2+<\/jats:sup> lead to vasoconstriction, whereas an increase of cAMP induces vasodilatation. Here we investigated whether Ca<jats:sup>2+<\/jats:sup> interferes with cAMP signaling by regulation of phophodiesterases (PDEs) or adenylyl cyclases (ACs). We studied regulation of cAMP concentrations by Ca<jats:sup>2+<\/jats:sup> signals evoked by endogenous purinergic receptors in vascular smooth muscle cells (VSMCs). The fluorescence resonance energy transfer (FRET)-based cAMP sensor Epac1-camps allowed the measurement of cAMP levels in single-living VSMCs with subsecond temporal resolution. Moreover, in vitro calibration of Epac1-camps enabled us to estimate the absolute cytosolic cAMP concentrations. Stimulation of purinergic receptors decreased cAMP levels in the presence of the \u03b2-adrenergic agonist isoproterenol. Simultaneous imaging of cAMP with Epac1-camps and of Ca<jats:sup>2+<\/jats:sup> with Fura 2 revealed a rise of intracellular Ca<jats:sup>2+<\/jats:sup> in response to purinergic stimulation followed by a decline of cAMP. Chelation of intracellular Ca<jats:sup>2+<\/jats:sup> and overexpression of Ca<jats:sup>2+<\/jats:sup>-independent AC4 antagonized this decline of cAMP, whereas pharmacological inhibition of Ca<jats:sup>2+<\/jats:sup>-activated PDE1 had no effect. AC assays with VSMC membranes revealed a significant attenuation of isoproterenol-stimulated cAMP production by the presence of 2 \u03bcM Ca<jats:sup>2+<\/jats:sup>. Furthermore, small interfering RNA (siRNA) knockdown of AC5 and AC6 (the two ACs known to be inhibited by Ca<jats:sup>2+<\/jats:sup>), significantly reduced the decrease of cAMP upon purinergic stimulation of isoproterenol-prestimulated VSMCs. Taken together, these results implicate a Ca<jats:sup>2+<\/jats:sup>-mediated inhibition of AC5 and 6 as an important mechanism of purinergic receptor-induced decline of cAMP and show a direct cross talk of these signaling pathways in VSMCs. <\/jats:p>","DOI":"10.1152\/ajpcell.00197.2009","type":"journal-article","created":{"date-parts":[[2009,11,5]],"date-time":"2009-11-05T03:39:28Z","timestamp":1257392368000},"page":"C324-C332","source":"Crossref","is-referenced-by-count":25,"title":["G<sub>q<\/sub>-mediated Ca<sup>2+<\/sup> signals inhibit adenylyl cyclases 5\/6 in vascular smooth muscle cells"],"prefix":"10.1152","volume":"298","author":[{"given":"Kathrin","family":"von Hayn","sequence":"first","affiliation":[{"name":"University of W\u00fcrzburg, Institute of Pharmacology and Toxicology, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth C.","family":"Werthmann","sequence":"additional","affiliation":[{"name":"University of W\u00fcrzburg, 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