The role of Na+ in muscarinic receptor-mediated catecholamine secretion in the absence of extracellular Ca2+ in cat perfused adrenal glands.

1. The role of Na+ in muscarinic receptor-mediated catecholamine secretion, which is independent of extracellular Ca2+, was investigated by observing the effect of veratridine and ouabain in perfused adrenal glands of the cat. 2. Veratridine (10(-4) M) markedly enhanced catecholamine secretion evoked by acetylcholine (ACh, 10(-4) M) during perfusion with Ca2(+)-free Locke solution containing hexamethonium (10(-3) M). The enhancement tended to be larger for noradrenaline secretion than for adrenaline secretion. Qualitatively the same result was obtained in the response to pilocarpine (5 x 10(-4) M). 3. Ouabain (10(-4) M) also enhanced ACh- and pilocarpine-induced catecholamine secretions, especially noradrenaline secretion in the absence of extracellular Ca2+. 4. Tetrodotoxin (10(-6) M) blocked the enhancing effect of veratridine on ACh-induced catecholamine secretion, but not that of ouabain in the absence of extracellular Ca2+. 5. When NaCl was replaced with sucrose, there was no secretory response to ACh regardless of the presence or absence of veratridine or ouabain. However, when ouabain, but not veratridine, was infused with Na+ before the replacement of NaCl, the response to ACh was substantially augmented. 6. These results indicate that Na+ is essential in the initiation of muscarinic receptor-mediated catecholamine secretion and its enhancement by veratridine and ouabain in the absence of extracellular Ca2+. Both drugs seem to increase the intracellular concentration of Na+ through different mechanisms and result in increases in the efficiency of Ca2+ mobilization from intracellular Ca2+ pools linked to muscarinic receptors.