Sodium-dependence of the potency of inhibitors of the neuronal noradrenaline carrier in the rat vas deferens.
Vasa deferentia obtained from reserpine-pretreated rats were incubated (monoamine oxidase and catechol-O-methyltransferase inhibited) in media containing various concentrations of 3H-(-)noradrenaline and Na+ and initial rates of the neuronal uptake of 3H-noradrenaline measured both in the absence and presence of uptake inhibitors after 1 min of incubation. When rates of uptake were determined at various 3H-noradrenaline (1.0-12.2 mumol/l) and two fixed Na+ concentrations (25 and 140 mmol/l), the inhibition of uptake produced by (+)amphetamine, (-)metaraminol, desipramine, nomifensine and cocaine was competitive with respect to 3H-noradrenaline at both Na+ concentrations. While the Ki for (+)amphetamine, (-)metaraminol desipramine and nomifensine increased when the Na+ concentration was lowered, that for cocaine decreased. When the Na+ concentration was varied (10-140 mmol/l) and the 3H-noradrenaline concentration held constant (1.2 mumol/l), (+)amphetamine, (-)metaraminol, nomifensine and desipramine acted as mixed-type inhibitors with respect to Na+, and the inhibition of uptake produced by these drugs was the more pronounced, the higher the Na+ concentration. On the other hand, cocaine was competitive with Na+ and the inhibition produced by this drug was the more pronounced, the lower the Na+ concentration. It is concluded that the inhibitors of neuronal uptake tested here act in dependence on the external Na+ concentration. Desipramine and nomifensine resemble alternative amine substrates in being more potent at high than at low Na+ concentrations. On the other hand, cocaine is more potent at low than at high Na+ concentrations.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000502:physiology*; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism
D012964:Sodium; D003042:Cocaine; D003891:Desipramine; D009638:Norepinephrine