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Adenosine and adenosine uptake inhibitors potentiate the neuromuscular blocking action of rocuronium mediated by adenosine A 1 receptors in isolated rat diaphragms
Author(s) -
NARIMATSU E.,
NIIYA T.,
KAWAMATA M.,
NAMIKI A.
Publication year - 2008
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/j.1399-6576.2008.01714.x
Subject(s) - adenosine , rocuronium , ccpa , adenosine a1 receptor , adenosine receptor , medicine , agonist , pharmacology , neuromuscular transmission , endocrinology , receptor , propofol
Background: Adenosine, which pre‐junctionally modulates neuromuscular transmission, and adenosine uptake inhibitors, which increase extracellular adenosine, have been used clinically. We investigated the effects of adenosine, dipyridamole and midazolam on the neuromuscular blocking action of rocuronium. Methods: Isometric twitch tensions of rat nerve‐hemidiaphragm preparations elicited by indirect (phrenic nerve) supra‐maximal stimulation at 0.1 Hz were evaluated ( n =6 in all data). Results: Pre‐treatments with adenosine (0.1 and 1 μM) and CCPA (1 μM, adenosine A 1 receptor agonist), but not that with CGS21680 (0.5 μM, A 2 receptor agonist), shifted the rocuronium concentration–twitch tension curves to the left and decreased the rocuronium concentration for 50% twitch depression (IC 50 ) compared with the control ( P <0.01). The leftward shift induced by 1 μM adenosine was inhibited by pre‐treatments with theophylline (50 μM, non‐selective adenosine receptor antagonist) and DPCPX (0.2 μM, A 1 receptor antagonist) but not by that with DPMA (5 μM, A 2 receptor antagonist). Pre‐treatments with dipyridamole and midazolam, adenosine uptake inhibitors, shifted the curve to the left and decreased IC 50 at supra‐therapeutic concentrations (10 and 2.5 μM, respectively) but not at clinical concentrations (2 and 0.5 μM, respectively), and the leftward shifts were inhibited by pre‐treatment with DPCPX (0.2 μM). Conclusion: The results indicate that adenosine potentiates the neuromuscular blocking action of rocuronium mediated by adenosine A 1 receptors and that supra‐therapeutic concentrations of dipyridamole and midazolam also potentiate the action of rocuronium by increasing endogenous adenosine concentration.