MODULATION BY PRESYNAPTIC ADENOSINE A(1) RECEPTORS OF NICOTINIC RECEPTOR ANTAGONIST-INDUCED NEUROMUSCULAR BLOCK IN THE MOUSE

We have investigated how altering the activation of adenosine A(1) rec eptors modifies nicotinic receptor antagonist-induced fade of tetanic contractions in the mouse isolated hemi-diaphragm. Vecuronium-induced tetanic fade was attenuated by an adenosine A(1) receptor antagonist ( 8-cyclopentyl-1,3-dipropylxanthine, DPCPX, 10(-7) M) and by an inhibit or of the synthesis of extracellular adenosine from ATP (alpha,beta-me thylene ADP, MeADP, 5 x 10(-5) M). Conversely, vecuronium-induced teta nic fade was potentiated by an adenosine A(1) receptor agonist (N-6-cy clohexyladenosine, CHA, 10(-7) M) and an inhibitor of the extracellula r destruction of adenosine (erythro-9-[2-hydroxy-3-nonyl]adenine, EHNA , 10(-4) M). The ability of an adenosine A(1) receptor antagonist to a ttenuate 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 teta nic fade indicates that this endogenous adenosine is derived from ATP. Hexamethonium-induced tetanic fade was also potentiated by increasing adenosine A(1) receptor activation, albeit with a higher concentratio n of CHA (10(-4) M). However, unlike for vecuronium, hexamethonium-ind uced tetanic fade was not attenuated by reducing adenosine A(1) recept or activation. This latter observation suggests that the tetanic fade produced by hexamethonium and vecuronium does not share a common mecha nism of action.