Blackwell Publishing Journal Backfiles 1879-2005
1. The effects of κ opioid receptor stimulation on cardiac rhythm and the underlying signal pathways were investigated in the rat.2. Stimulation of κ opioid receptors with 40–50 μmol/L U50 488H, a selective κ opioid receptor agonist, induced dysrhythmias and increased inositol 1,4,5-trisphosphate (IP3) production in rat isolated, perfused heart. The pro-arrhythmic effects of U50 488H were abolished by 5 μmol/L nor- binaltorphimine (nor-BNI), a specific κ opioid receptor antagonist.3. The effect of U50 488H on cardiac dysrhythmia and IP3 production were abolished by 1 mmol/L neomycin and streptomycin, phospholipase C (PLC) inhibitors.4. At 1 μmol/L, U50 488H, which itself has no effect on cardiac rhythm and IP3 production, significantly attenuated the potentiating effect of 1 μmol/L noradrenaline (NA) on dysrhythmias, which were induced by low flow in the isolated heart. The effects of U50 488H were abolished by 1 μmol/L nor-BNI. Cytosolic cAMP production was augmented by 1 μmol/L NA and this was significantly attenuated by 1 μmol/L U50 488H.5. At 1 μmol/L, U50 488H also reduced [Ca2+]i oscillations induced by 0.5 μmol/L NA and 0.5 μmol/L forskolin, an activator of adenylate cyclase (AC).6. In conclusion, U50 488H exerted pro- and anti-arrhythmic actions at high and lower concentrations, respectively. The former effect was mediated via the PLC/IP3 pathway, while the latter was mediated via the AC/cAMP pathway.
Type of Medium: