Abstract

The importance of Na+ in the ouabain-induced increase in noradrenaline output from adrenergic nerve terminals of the guinea-pig vas deferens was investigated during incubation in standard Krebs solution and Sr2+- and Ba2+-substituted Krebs solutions. Ouabain (10(-4) M) caused a gradual increase in noradrenaline output regardless of the type of divalent cation used. The rate of development of the ouabain-induced noradrenaline output and the maximum amount released depended on the divalent cation present (Ba2+ greater than Sr2+ greater than Ca2+). The magnitude of the ouabain-induced response depended on the concentration of extracellular Na+. The sensitivity of the ouabain-induced response to a change in Na+ concentration depended on the divalent cation present (Ca2+ greater than Sr2+ greater than Ba2+). Tetrodotoxin (1.6 x 10(-6) M) delayed the onset, whereas monensin (10(-5) M) hastened it. The maximum level of the ouabain-induced response was attenuated by monensin in all the incubation solutions. These results suggest that Na+ entry into adrenergic nerve terminals through tetrodotoxin-sensitive mechanisms is crucial for the increase in noradrenaline output due to ouabain when extracellular Ca2+ is replaced with Sr2+ or Ba2+.

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