The cat adrenal gland was retrogradely perfused with a medium lacking divalent cation, and the secretion of catecholamines was induced by Ca reintroduction with or without simultaneous removal of external Na. These responses were markedly reduced after prior exposure to a medium containing Mg (1 mM) or lacking Na. The inhibition caused by Mg was reversed by ouabain treatment. Reversing the concentration gradient for Na alone by replacing external Na with Tris, choline, or Li did not stimulate catecholamine secretion when Ca2+ (0.1 mM) was present in the external medium throughout the experiment. However, the treatment with ouabain reversed this inhibitory effect of Ca so that Na removal did induce marked secretion. Essentially similar results concerning secretion were obtained in the cultured bovine chromaffin cells. There was a reasonable correlation between secretion and 45Ca uptake in these cells under various experimental manipulations, and alterations of these parameters were well correlated with the level of internal Na. Furthermore, the rate constant of 22Na efflux was found to increase when Ca was reintroduced with the simultaneous removal of Na during exposure to a medium containing ouabain. These results are consistent with the view that the mechanism of internal Na-dependent Ca influx is activated to induce catecholamine secretion whenever internal Na is raised above a critical level. On the other hand, there were significant increases in the catecholamine secretion and 45Ca uptake which were induced by substitution of NaCI with sucrose, even when the operation of the internal Nadependent Ca influx mechanism was markedly restricted by various experimental manipulations. This suggests that other secretory mechanisms are involved under these conditions. This would account for the largest secretory effect of sucrose substitution under the condition in which internal Na-dependent Ca influx is activated.
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.
Release of CA and dopamine‐β‐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.
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.
Sr or Ba substituted for Ca in maintaining secretion by Na‐free (sucrose) medium.
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.
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.
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.
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.
All the Na substitutes tested increased secretion of CA and 45Ca uptake, in a parallel fashion.
A correlation between secretion and 45Ca uptake was found under various experimental manipulations which reduced secretion of CA.
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.
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.
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