Cholinesterase activity and exposure time to acetylcholine as factors influencing the muscarinic inhibition of [³H]‐noradrenaline overflow from guinea‐ pig isolated atria

Abstract

1 Guinea-pig isolated atria were incubated and loaded with [3H]-noradrenaline. The release of 3H and of [3H]-noradrenaline was induced by field stimulation (6-9 trains of 150 pulses at 5 Hz). The stimulation-evoked overflows of 3H and of [3H]-noradrenaline were determined. 2 In the absence of an inhibitor of acetylcholinesterase, acetylcholine (12 min preincubation before nerve stimulation, up to 10pM) failed to inhibit the evoked [3H]-noradrenaline overflow. In the presence of atropine, an increase by acetylcholine of evoked release was observed in the same atria. In contrast, the selective muscarinic agonist methacholine significantly decreased the evoked overflow. 6 It is concluded that a muscarinic inhibition by acetylcholine (upon prolonged exposure time) may be masked by a concomitant facilitation of release and/or desensitization of the muscarinic inhibitory mechanism. Furthermore, degradation by acetylcholinesterase contributes in part to the ineffectiveness of acetylcholine as a presynaptic inhibitor. When a distortion of the overflow/release ratio was excluded, adrenergic and nicotinic effects were prevented, and acetylcholinesterase was inhibited, the fading of muscarinic inhibition by acetylcholine may have been exclusively due to a slow and moderate desensitization of the presynaptic muscarinic mechanism.

Presynaptic muscarinic receptors inhibiting endogenous noradrenaline release in the portal vein of the freely moving rat

“…(Daemen et al, 1989) (Muscholl et al, 1979). Fuder et al (1985) also demonstrated an inhibition of the NA overflow using this selective muscarinic agonist at concentrations of 1 and 10 M in guinea-pig isolated atria. In our model, infusion of MCh (0.3pgmin-1) has no effect on the basal NA level, indicating that possible interfering effects of MCh like vasodilatation or bradycardia have no influence on the plasma NA level measured in the portal vein.…”