Monovalent cation dependency for the inhibition of outward transport of [ 3H]norepinephrine

Abstract

Rat hearts were labelled with [ 3H]norepinephrine in vivo. Slices of ventricles were prepared, preincubated in Krebs-HCO 3 medium (KRB), and then incubated in a Na +-deficient, choline +-Krebs HCO 3 (Ch +-Ca 2+). The choline +-Krebs HCO 3 medium induced a delayed neurosecretion which could be inhibited by either one of the blockers of the uptake of NE, cocaine or desipramine, when included in both the Krebs and the Ch +-Ca 2+. When either desipramine or cocaine was present in the Na +-rich preincubation medium only, the duration of action of desipramine was more prolonged than that of cocaine. When desipramine was first added to the Ch +-Ca 2+ medium at various times after incubation, the inhibitory response became smaller as the duration of preliminary Na +-deprivation was increased. After incubation for 80 min neither desipramine nor cocaine inhibited secretion. Sodium (added to Ch +-Ca 2+ medium or in a Krebs replacement medium) then slowed the rate of release stimulated by Ch +-Ca 2+ and facilitated an inhibitory action for both inhibitors. The inhibition did not require the continued presence of Na +. Depolarizing concentrations of K + in the Ch +-Ca 2+ medium with Na + and either one of the inhibitors, prevented the inhibition of neurosecretion. However, K + which was added to the preincubation medium with either inhibitor did not prevent the prolonged inhibition of neurosecretion. By contrast with the secretory response to Ch +-Ca 2+, the secretory response to K + in Na +-enriched Ch +-Ca 2+ medium was weakly inhibited by the inhibitors of transport.