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.
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+.
Nakazato
Y
Y
Department of Veterinary Pharmacology, Obihiro University of Agriculture and Veterinary Medicine, Japan.
Ito
S
S
Ohga
A
A
D000818:Animals; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002413:Cations, Divalent; D006168:Guinea Pigs; D008297:Male; D008985:Monensin / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology*; D012964:Sodium / Q000494:pharmacology; D013324:Strontium / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology*; D013997:Time Factors; D014649:Vas Deferens / Q000378:metabolism*
D002413:Cations, Divalent; D001464:Barium; D013779:Tetrodotoxin; D010042:Ouabain; D008985:Monensin; D012964:Sodium; D002118:Calcium; D009638:Norepinephrine; D013324:Strontium