title: β-Adrenergic receptor signaling increases NAADP and cADPR levels in the heart.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Lewis
authors.forename: Parvinder K
authors.initials: PK
authors.lastname: Aley
authors.forename: Ali
authors.initials: A
authors.lastname: Roomi
authors.forename: Justyn M
authors.initials: JM
authors.lastname: Thomas
authors.forename: Roser
authors.initials: R
authors.lastname: Masgrau
authors.forename: Clive
authors.initials: C
authors.lastname: Garnham
authors.forename: Katherine
authors.initials: K
authors.lastname: Shipman
authors.forename: Claire
authors.initials: C
authors.lastname: Paramore
authors.forename: Duncan
authors.initials: D
authors.lastname: Bloor-Young
authors.forename: Luke E L
authors.initials: LE
authors.lastname: Sanders
authors.forename: Derek A
authors.initials: DA
authors.lastname: Terrar
authors.forename: Antony
authors.initials: A
authors.lastname: Galione
authors.forename: Grant C
authors.initials: GC
authors.lastname: Churchill
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D036563:Cyclic ADP-Ribose / Q000378:metabolism*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism*; D009249:NADP / Q000031:analogs & derivatives* / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D036563:Cyclic ADP-Ribose; D009249:NADP; C024376:NAADP