Sodium-dependence of the saturability of carrier-mediated noradrenaline efflux from noradrenergic neurones in the rat vas deferens

Abstract

The carrier-mediated transport of 3H-noradrenaline out of noradrenergic neurones was studied in vasa deferentia obtained from rats after pretreatment with reserpine and pargyline (to inhibit vesicular storage and monoamine oxidase, respectively). The tissue was first preincubated with various concentrations of 3H-noradrenaline (0.3--100 mumol/1; 30 min) and then washed out for 110 min with amine-free medium. During the last 10 min of washout, carrier-mediated neuronal efflux of 3H-noradrenaline was elicited by exposure to either Na+-free medium or 100 mumol/l veratridine; it was measured at 1-min intervals. While the peak rates of carrier-mediated 3H-noradrenaline efflux elicited by Na+-free medium were linearly related to the 3H-noradrenaline content of the tissue (which cannot be raised beyond a certain maximal value, since uptake is saturable), those evoked in response to veratridine approached saturation as the 3H-noradrenaline level in the tissue was raised. Hence, saturation of 3H-noradrenaline outward transport was demonstrated at high (exposure to veratridine), but not at low (exposure to Na+-free medium) intraneuronal Na+ concentrations. The results indicate that the Km for the mediated outward transport of noradrenaline across the plasma membrane of noradrenergic neurones is inversely related to the internal Na+ concentration, just as the Km for the mediated inward transport of noradrenaline (i.e., the neuronal noradrenaline uptake) is inversely related to the external Na+ concentration.