Sodium ions inhibit the stimulant action of caffeine on catecholamine secretion from adrenal chromaffin cells of the guinea pig.

Catecholamine secretion evoked by caffeine (40 mM) was markedly enhanced by replacing NaCl in the medium with sucrose or KCl in the absence, but not in the presence, of extracellular Ca2+ and Mg2+ in both perfused adrenal glands and isolated chromaffin cells of the guinea pig. The response to caffeine declined on repetition, but was restored completely after readmission of Ca2+. These results indicate that extracellular Na+ inhibits caffeine from stimulating catecholamine secretion, which may be mediated by a release of Ca2+ from intracellular storage sites in the adrenal chromaffin cells in the presence of extracellular Ca2+ and/or Mg2+.