Evidence suggests that β-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 β-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 β-adrenergic receptor signaling pathway.
Journal article
2012-10-19T00:00:00+00:00
427
326 - 329
3
Adrenergic beta-Agonists, Animals, Cyclic ADP-Ribose, Guinea Pigs, Heart, In Vitro Techniques, Myocardium, NADP, Receptors, Adrenergic, beta, Signal Transduction