Metabolism of [3H]-(+/-)-isoprenaline by isolated atria and coronary arteries of the kitten

Abstract

1 Isolated coronary arteries of the kitten accumulated more unchanged isoprenaline and metabolized more amine than atria following incubation for 1 to 20 min with [3H]-(+/-)-isoprenaline (25 ng/ml or 5 micrograms/ml). 2 Cortisol (10 or 80 microM), U-0521 (120 microM) and oxytetracycline (100 microM) all reduced metabolite formation. 3 Cortisol inhibited 'Iso InfluxMin' (cellular isoprenaline accumulation plus total metabolite production). In contrast, it increased, decreased or did not alter accumulation of unmetabolized isoprenaline, depending upon the experimental conditions. 4 Isoprenaline accumulation was increased in atria and reduced in coronary arteries by U-0521, while oxytetracycline reduced accumulation in coronary arteries at the high amine concentration. 5 It is concluded that in atria, cortisol inhibits metabolism and has differential effects on a number of extraneuronal compartments which accumulate isoprenaline. Both cortisol and U-0521 appear to be extraneuronal uptake inhibitors and inhibitors of catechol-O-methyltransferase in coronary arteries. Oxytetracycline may have effects additional to inhibition of isoprenaline binding to connective tissue fibres.