K+-depolarization: an alternative method of inhibiting extraneuronal uptake on isolated tissue preparations?

Responses to isoprenaline were not potentiated by extraneuronal uptake (ENU) inhibitor drugs (phenoxybenzamine and metanephrine) in preparations of guinea-pig uterus which were contracted by K+-Krebs solution. Fluorescence histochemical experiments demonstrated that isoprenaline could accumulate extraneuronally in uterine smooth muscle and that this accumulation was inhibited by phenoxybenzamine and metanephrine. However, accumulation was also inhibited by K+-Krebs solution. Therefore, it was concluded that the failure of ENU inhibitor drugs to potentiate isoprenaline responses on K+-depolarized uterine preparations might occur because the uptake mechanism had already been inhibited by the K+-Krebs solution. Support for this hypothesis was obtained from experiments on guinea-pig tracheal preparations in which ENU inhibitor drugs had previously been shown to potentiate isoprenaline responses. In K+-depolarized tracheal preparations this potentiation did not occur presumably because the K+-Krebs solution had already inhibited the uptake. Thus K+-depolarization of a tissue may provide an alternative to the use of extraneuronal uptake inhibitor drugs when it is necessary to eliminate this site of loss in quantitative studies on beta-adrenoceptors in isolated tissues.