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 loca l anaesthetics to inhibit the cholinergic synaptic transmission using cultured bovine adrenal chromaffin cells, and to clarify if the inhibi tory action would correlate with biophysical and pharmacological prope rties. Local anaesthetics (bupivacaine, etidocaine, tetracaine, lignoc aine and procaine; 0-02-2 mm) inhibited carbachol-induced catecholamin e release from the cells in a concentration-dependent manner. This inh ibition was completely reversible. IC50 (concentration of 50% inhibiti on) of each anaesthetic showed no correlation with the lipid solubilit y. The local anaesthetics showed greater inhibitory potency at a highe r extracellular pH. The results suggest that clinically relevant conce ntrations of local anaesthetics inhibit the stimulus-secretion couplin g in the chromaffin cells. The un-ionized base form plays a major role , and the inhibitory potency does not depend on the lipid solubility o f the anaesthetics.