Monovalent cation dependency for the inhibition of outward transport of [3H]norepinephrine.
Rat hearts were labelled with [3H]norepinephrine in vivo. Slices of ventricles were prepared, preincubated in Krebs-HCO3 medium (KRB), and then incubated in a Na+-deficient, choline+-Krebs HCO3 (Ch+-Ca2+). The choline+-Krebs HCO3 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+-Ca2+. 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+-Ca2+ 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+-Ca2+ medium or in a Krebs replacement medium) then slowed the rate of release stimulated by Ch+-Ca2+ 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+-Ca2+ 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+-Ca2+, the secretory response to K+ in Na+-enriched Ch+-Ca2+ medium was weakly inhibited by the inhibitors of transport.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D002794:Choline / Q000378:metabolism / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009489:Neurosecretion / Q000187:drug effects*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000502:physiology; D013997:Time Factors
D012964:Sodium; D003042:Cocaine; D002794:Choline; D011188:Potassium; D002118:Calcium; D003891:Desipramine; D009638:Norepinephrine