EFFECTS OF TETRODOTOXIN AND MONENSIN ON THE NORADRENALINE OUTPUT INDUCED BY OUABAIN FROM THE GUINEA-PIG VAS DEFERENS IN THE PRESENCE OF VARIOUS DIVALENT CATIONS

¹ Department of Veterinary Pharmacology, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080
² Department of Pharmacology, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060, Japan

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⁺ Sr²⁺ 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⁺ Sr²⁺ 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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