title: Modulation by presynaptic adenosine A1 receptors of nicotinic receptor antagonist-induced neuromuscular block in the mouse.
abstract: We have investigated how altering the activation of adenosine A1 receptors modifies nicotinic receptor antagonist-induced fade of tetanic contractions in the mouse isolated hemi-diaphragm. Vecuronium-induced tetanic fade was attenuated by an adenosine A1 receptor antagonist (8-cyclopentyl-1,3-dipropylxanthine, DPCPX, 10(-7) M) and by an inhibitor of the synthesis of extracellular adenosine from ATP (alpha,beta-methylene ADP, MeADP, 5 x 10(-5) M). Conversely, vecuronium-induced tetanic fade was potentiated by an adenosine A1 receptor agonist (N6-cyclohexyladenosine, CHA, 10(-7) M) and an inhibitor of the extracellular destruction of adenosine (erythro-9-[2-hydroxy-3-nonyl]adenine, EHNA, 10(-4) M). The ability of an adenosine A1 receptor antagonist to attenuate vecuronium-induced tetanic fade indicates that a component of this fade is due to endogenous adenosine. Further, the ability of the inhibitor of adenosine synthesis to attenuate vecuronium-induced tetanic fade indicates that this endogenous adenosine is derived from ATP. Hexamethonium-induced tetanic fade was also potentiated by increasing adenosine A1 receptor activation, albeit with a higher concentration of CHA (10(-4) M). However, unlike for vecuronium, hexamethonium-induced tetanic fade was not attenuated by reducing adenosine A receptor activation. This latter observation suggests that the tetanic fade produced by hexamethonium and vecuronium does not share a common mechanism of action.
authors.affiliation: Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, UK. c.b.prior@strath.ac.uk
authors.forename: C
authors.initials: C
authors.lastname: Prior
authors.forename: E L
authors.initials: EL
authors.lastname: Breadon
authors.forename: K E
authors.initials: KE
authors.lastname: Lindsay
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018738:Hexamethonium / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019148:Neuromuscular Blockade; D009469:Neuromuscular Junction / Q000187:drug effects*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D058915:Purinergic P1 Receptor Antagonists; D017661:Receptors, Presynaptic / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000187:drug effects* / Q000378:metabolism; D013746:Tetany / Q000503:physiopathology; D014673:Vecuronium Bromide / Q000494:pharmacology*; D014970:Xanthines / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D018733:Nicotinic Antagonists; D058915:Purinergic P1 Receptor Antagonists; D017661:Receptors, Presynaptic; D018047:Receptors, Purinergic P1; D014970:Xanthines; D018738:Hexamethonium; C010192:9-(2-hydroxy-3-nonyl)adenine; D014673:Vecuronium Bromide; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000225:Adenine