CATECHOLAMINE UPTAKE BY ISOLATED CORONARY ARTERIES AND ATRIA OF THE KITTEN

Abstract

1 Kitten coronary arteries and atria incubated with [3H]-(-)-noradrenaline or [3H]-(±)-isoprenaline showed concentration- and temperature-dependent accumulation of amines (unchanged and/or as metabolites). In addition, coronary arteries incubated with [3H]-(+)-isoprenaline showed temperature-insensitive amine accumulation due to binding to connective tissue fibres. 2 With low concentrations of [3H]-(-)-noradrenaline (20 ng/ml) accumulation of radioactivity in both tissues was neuronal since it was reduced by desipramine, metaraminol or cocaine but not by the extraneuronal inhibitor, cortisol. 3 In coronary arteries incubated with [3H]-(±)-isoprenaline (5 jig/ml) for 1 or 10 min, uptake was extraneuronal since it was inhibited by cortisol, 17, B-oestradiol or phenoxybenzamine. 4 Atria incubated with (±)-isoprenaline (5 to 1000 jig/ml) showed non-neuronal, biphasic accumulation of amine. There was a high capacity, low affinity initial uptake process (apparent Km 136 gM) which was resistant to steroidal extraneuronal uptake inhibitors but which could be abolished by phenoxybenzamine. A slower uptake occurred after 2 min which was sensitive to steroidal and other extraneuronal uptake inhibitors. 5 Inhibition of uptake processes did not alter sensitivity of coronary arteries to dilator effects of catecholamines. However, experiments with extraneuronal uptake inhibitors were limited by the relaxant effects of cortisol and 17f3-oestradiol themselves. 6 In atria inhibition of neuronal uptake by desipramine or cocaine led to super-sensitivityto (-)-noradrenaline but not to (-)-adrenaline or (±)-isoprenaline. Chronotropic responses to (-)-noradrenaline were increased five fold and inotropic responses three fold. 7 Inhibition of extraneuronal uptake led to selective super-sensitivityto (±)-isoprenaline. Cortisol increased chronotropic responses ten fold and inotropic responses three fold, while 17f-oestradiol produced less than two fold increases in sensitivity to isoprenaline.