In Vitro Effects of Gallamine on Dissociation Kinetics of (³H) N-Methylscopolamine and (³H) Pirenzepine from Rat Brain Muscarinic Receptors

Abstract

Gallamine inhibited the binding of both (³H) N-Methylscopolamine ((³H)NMS) and (³H) Pirenzepine ((³H)PZ) in the hippocampus, striatum and cortex of rat brain. Competition curves between gallamine and (³H)PZ suggested that gallamine recognized an homogeneous class of receptors (Hill coefficient close to 1) whereas competition curves, using (³H) NMS as tracer, were compatible with two classes of gallamine receptors (Hill coefficient below 0.7). The latter phenomenon could be explained, at least partially, by the inhibitory effect exerted by gallamine on the k_off of (³H)NMS. This effect was already observed at a 10 μM gallamine concentration and reached 100% at 1 mM (a gallamine concentration reducing the k_off of (³H) PZ by 30 % only). The nature of the radioligand rather than the relative abundance of M₁—M₂ receptors was probably responsible for this discrepancy.

Gallamine inhibited the (³H) NMS dissociation rate from brain M₁ and M₂ receptors (i.e. receptors with high and intermediate affinity for pirenzepine) with a lower potency than from cardiac M₂ receptors (i.e. receptors with low affinity for pirenzepine).