Release of [3H]noradrenaline from perfused rat hearts by potassium and its modifications by 6-hydroxydopamine and reserpine.
The sources of noradrenaline (NA) released by excess potassium from isolated perfused rat hearts were investigated by labelling the hearts from normal, reserpine-treated, and 6-hydroxydopamine-treated (6-OHDA-treated) rats with [3H]HA, and measuring the increased rate of efflux induced by perfusion with a Krebs solution containing varying amounts of excess potassium. The [3H]NA and its metabolites in the effluent were separated by adsorption on alumina and a cation-exchange resin (Dowex-50). The release induced by potassium was a linear function of the log of the increased potassium concentration. Following a 1-h efflux period after labelling with [3H]NA, the hearts from reserpine-treated rats retained 1/5 as much [3H]NA, and released, in response to a 56mM elevation in the potassium concentration, less than 1/6 as much tritium label as the hearts from untreated (control) animals. In contrast, the hearts form 6-OHDA-treated animals retained 1/15 of the amount of [3H]NA and released 1/50 of the 3H label as did the control hearts. The potassium-induced increase of 3H-labelled substances in the effluent from the control hearts showed a large (threefold) percentage increase in the [3H]NA fraction, whereas the effluents from the hearts of reserpine- and 6-OHDA-treated animals contained only small increases in the [3H]NA fraction. Based on the assumptions that reserpine prevented retention of NA in the storage granules whereas 6-OHDA prevented almost all neuronal storage, it was concluded that more than 80% of the NA released by potassium excess from perfused normal hearts originated from the storage vesicles of the nerves, the remainder being largely from the cytoplasm of the nerves, with only a small portion from extraneuronal sources.
D000818:Animals; D006321:Heart / Q000187:drug effects; D006892:Hydroxydopamines / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D012110:Reserpine / Q000494:pharmacology*; D013997:Time Factors
D006892:Hydroxydopamines; D012110:Reserpine; D011188:Potassium; D009638:Norepinephrine