Abstract

The uptake of the two erythro and two threo isomers of metaraminol (MA) by rabbit heart slices is a Na⁺-dependent process. Of the four stereoisomers, only the uptake of (—)-erythro-MA (l-MA) in low [Na⁺] is markedly decreased by reserpine. The effect of reserpine on l-MA uptake at low [Na⁺] is relatively short-lived as compared with the effect of the drug on endogenous catecholamine levels. Thus, 48 hours after reserpine, l-MA uptake in low [Na⁺] was essentially unaltered. Tetrabenazine also potentiated the inhibitory effect of low [Na⁺] on l-MA uptake, and competitive studies suggest that reserpine and tetrabenazine share the same site of action on the optically specific amine carrier mechanism. Guanethidine, under conditions which greatly inhibited the intraneuronal granular storage mechanism, had no effect on l-MA uptake at low [Na⁺]. Hence, the ability to inactivate the optically specific reserpine-sensitive amine carrier system is a specific effect not possessed by all drugs which decrease endogenous catecholamine levels. Bretylium and debrisoquin, at doses evoking adrenergic neuron blockade, also had no effect on l-MA uptake at low [Na⁺]. It is suggested that the Na⁺-dependent, optically specific and reserpine-sensitive amine carrier mechanism may constitute a component of the functional or "available" norepinephrine pool.