Mechanism of efflux of noradrenaline from adrenergic nerves in rabbit atria.

1. The mechanism of efflux of (-)-[(3)H]-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 [(3)H]-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.