EFFECT OF LOCAL-ANESTHETICS ON THE STIMULUS-SECRETION COUPLING IN BOVINE ADRENAL CHROMAFFIN CELLS

This study was carried out to determine the relative potencies of local anaesthetics to inhibit the cholinergic synaptic transmission using cultured bovine adrenal chromaffin cells, and to clarify if the inhibitory action would correlate with biophysical and pharmacological properties. Local anaesthetics (bupivacaine, etidocaine, tetracaine, lignocaine and procaine; 0-02-2 mm) inhibited carbachol-induced catecholamine release from the cells in a concentration-dependent manner. This inhibition was completely reversible. IC50 (concentration of 50% inhibition) of each anaesthetic showed no correlation with the lipid solubility. The local anaesthetics showed greater inhibitory potency at a higher extracellular pH. The results suggest that clinically relevant concentrations of local anaesthetics inhibit the stimulus-secretion coupling in the chromaffin cells. The un-ionized base form plays a major role, and the inhibitory potency does not depend on the lipid solubility of the anaesthetics.