ß-Adrenergic receptor signaling increases NAADP and cADPR levels in the heart
Lewis AM., Aley PK., Roomi A., Thomas JM., Masgrau R., Garnham C., Shipman K., Paramore C., Bloor-Young D., Sanders LEL., Terrar DA., Galione A., Churchill GC.
Evidence suggests that ß-Adrenergic receptor signaling increases heart rate and force through not just cyclic AMP but also the Ca 2+-releasing second messengers NAADP (nicotinic acid adenine dinucleotide phosphate) and cADPR (cyclic ADP-ribose). Nevertheless, proof of the physiological relevance of these messengers requires direct measurements of their levels in response to receptor stimulation. Here we report that in intact Langendorff-perfused hearts ß-adrenergic stimulation increased both messengers, with NAADP being transient and cADPR being sustained. Both NAADP and cADPR have physiological and therefore pathological relevance by providing alternative drug targets in the ß-adrenergic receptor signaling pathway. © 2012 Elsevier Inc.