Involvement of uptake2 in the termination of activity of neurogenic noradrenaline in the rat isolated atrium.

Abstract

1. An examination has been made of the relative effect of drugs which affect Uptake1 and Uptake2 on the mechanical responses to adrenergic nervous stimulation (0-5-5 Hz for 5 sec) in rat isolated atrium. 2. Inhibition of Uptake1 with desmethylimipramine (2 muM) prolonged by 50-90% the time taken for recovery of normal heart rate after a five sec train of nervous stimulation. Inhibition of Uptake2 with metanephrine (4 muM) prolonged by 20-40% the time taken for recovery of normal heart rate. 3. Neither desmethylimipramine nor metanephrine had any consistent effect on the time course of the inotropic response to stimulation or on the amplitudes of either inotropic or chronotropic responses. 4. After administration of desmethylimipramine, metanephrine had a somewhat greater effect on chronotropic responses than when given alone. After administration of metanephrine, desmethylimipramine still further prolonged chronotropic responses to low frequency stimulation (0-5, 1 Hz) but had no effect at 5 Hz. These results agree with the known affinities of each uptake process for different concentrations of noradrenaline in the rat heart. 5. It is concluded that both Uptake1 and Uptake2 participate in the termination of physiological activity of neurogenic noradrenaline in rat isolated atrium even at low frequencies of nervous activation. 6. No evidence was obtained to indicate that manipulation of circulating oestrogen levels by oöphorectomy and oestrogen-priming of female rats had any effect of the efficiency of the cardiac Uptake2 process.