Exocytotic secretion of catecholamines from the cat adrenal medulla by sodium deprivation: involvement of calcium influx mechanism.

1 Cat adrenal glands were perfused with Ca-deficient medium and secretion of catecholamines (CA) was induced by perfusion with Na-free medium in which NaCl was replaced by an osmotically equivalent amount of sucrose. 2 Release of CA and dopamine-beta-hydroxylase (DBH), but not that of phenylethanolamine-N-methyltransferase, was concomitantly found in the effluents when the adrenals were stimulated, indicating that secretion was due to exocytosis. 3 Secretion of CA induced by Na-free (sucrose) medium was dependent on the concentration of Ca and was saturated at 0.5 mM of Ca. 4 Sr or Ba substituted for Ca in maintaining secretion by Na-free (sucrose) medium. 5 The addition of Na, Li or alkali metal ions to Na-free (sucrose) medium containing Ca reduced the response to a variable extent but this inhibition was reversed by raising the concentration of Ca in the Na-free medium. 6 All of the Na substitutes used induced secretion only when this medium contained Ca. However, different Na substitutes released different amounts of CA; sucrose was most effective, K, Tris and choline were moderately and Li least effective. 7 Secretion of CA by Na-free (sucrose) medium was strongly inhibited by D-600, tetracaine or divalent cations such as Co, Ni, Zn and Mg. The inhibition by Co was partially reversed by raising the concentration of Ca in the Na-free medium. 8 Secretion of CA from bovine isolated chromaffin cells was induced by Na-deficient (sucrose) medium and was dependent on the concentrations of ionized Ca involved. 9 All the Na substitutes tested increased secretion of CA and 45Ca uptake, in a parallel fashion. 10 A correlation between secretion and 45Ca uptake was found under various experimental manipulations which reduced secretion of CA. 11 These results demonstrated that unlike the perfused bovine adrenals, the Ca influx mechanism is essential for secretion by Na deprivation in the perfused cat adrenals as it is in bovine isolated chromaffin cells. 12 It is suggested that Na deprivation increases Ca entry through the Ca channels by eliminating the competition between Na and Ca, and possibly by activating Ca influx linked with Na efflux.