[3H]noradrenaline release from rabbit pulmonary artery: sodium‐pump‐dependent sodium‐calcium exchange.

1. The release of [3H]noradrenaline ([3H]NA) from the isolated main pulmonary artery of the rabbit has been measured in the presence of neuronal (cocaine, 3 X 10(‐5) M) and extraneuronal (corticosterone, 5 X 10(‐5) M) uptake blockers. 2. K+ removal from the external medium increased the release of [3H]NA, an action transiently inhibited by Ca2+‐free (+1 mM‐EGTA) solution, i.e. after Ca2+ removal transmitter release was first abolished and then started to increase again after a delay lasting about 90‐120 min. 3. Ca2+ readmission to arteries which had been kept in Ca2+‐ and 'K+‐free' solution, markedly increased the [3H]NA release. The rate of transmitter release was dependent on the preceding perfusion period with 'K+‐free' solution, being greater for longer exposure times. 4. When Ca2+ and K+ were readmitted together to K+‐depleted and Na+‐enriched preparations, the release of [3H]NA transiently increased. 5. If K+ was readmitted first, the subsequently applied Ca2+ was ineffective in producing transmitter release. 6. Different alkali metal ions (Rb+, Cs+ or Li+) were also readmitted as K+ substitutes together with Ca2+. In all cases the release of neurotransmitter transiently increased; however, the rate of release was dependent on the monovalent cation used. Thus, Rb+ ions were as effective as, Cs+ about one‐third as effective as, and Li+ about one‐fifth as effective as K+ in activating the Na+ pump. 7. It is concluded that in the absence of external Ca2+, and in response to Na+‐pump inhibition, the release of Ca2+ from internal stores is responsible for the NA release observed. On readmission of Ca2+ the rate of transmitter release is dependent on the Na+ previously gained inside. Furthermore, the activity of the Na+ pump determines the rate of transmitter release through the Na‐Ca exchange mechanism.