Mechanism of efflux of noradrenaline from adrenergic nerves in rabbit atria

Abstract

1 The mechanism of efflux of (—)-[³H]-noradrenaline was examined in rabbit atria, which were pretreated with reserpine and pargyline. 2 Between 40 and 100 min, efflux occurred predominantly from a single intraneuronal compartment. 3 Efflux was rapidy increased by (—)- and (+)-noradrenaline, tyramine and (±)-metaraminol, but not by (±)-isopropylnoradrenaline or (±)-normetanephrine. The increase in efflux produced by (—)-noradrenaline was inhibited by cocaine and desipramine but not by lidocaine. 4 Spontaneous effluxes, and those accelerated by (—)-noradrenaline, were temperature-sensitive. 5 Efflux was increased by ouabain, omission of K⁺, metabolic inhibition and lowering of the external Na⁺ concentration. These effects were significantly reduced by cocaine and desipramine but not by lidocaine. 6 These findings provide evidence that the efflux of [³H]-noradrenaline from adrenergic nerves occurs by a cocaine-sensitive, carrier-mediated process. The characteristics of the efflux process are compatible with, but not conclusive proof for, the Na⁺-gradient hypothesis.