ß-Adrenergic receptor signaling increases NAADP and cADPR levels in the heart

Evidence suggests that ß-Adrenergic receptor signaling increases heart rate and force through not just cyclic AMP but also the Ca2+-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.

► We measured cADPR and NAADP in hearts during ß-adrenergic stimulation. ► ß-adrenergic stimulation increased both cADPR and NAADP. ► The increase in NAADP was transient whereas the increase in cADPR was sustained.