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

Abstract

SUMMARY1. An examination has been made of the relative effect of drugs which affect Uptake, and Uptake2 on the mechanical responses to adrenergic nervous stimulation (0.5-5 Hz for 5 see) in rat isolated atrium.2. Inhibition of Uptake1 with desmethylimipramine (2 ,UM) prolonged by 50-90% the time taken for recovery of normal heart rate after a five see train of nervous stimulation. Inhibition of Uptake2 with metanephrine (4#M) 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 o6phorectomy and oestrogen-priming of female rats had any effect on the efficiency of the cardiac Uptake2 process.

RELAXATION OF SMOOTH MUSCLE FOLLOWING CONTRACTION ELICITED BY SYMPATHETIC NERVE STIMULATION in vivo

“…The relaxation of smooth muscles after exposure to excitatory neurotransmitters is widely accepted to be dependent on the rate of inactivation of these agents within the tissue (Kalsner & Nickerson, 1968;Draskoczy & Trendelenburg, 1970;Trendelenburg & Henseling, 1976), and upon this assumption the mechanisms responsible for the inactivation of noradrenaline after its release from nerve terminals have been investigated in vitro (Brandao & Guimaraes, 1974;Bell & Grabsch, 1976).…”

Gamma‐aminobutyric acid uptake and the termination of inhibitory synaptic potentials in the rat hippocampal slice.

“…is consistent with our results. Similarly, Bell & Grabsch (1976) demonstrated that prolonged (> 25 s) chronotropic responses of rat heart to noradrenaline released in 5 s stimulus trains were prolonged by uptake inhibition.…”

Involvement of uptake1 and uptake2 in terminating the cardiovascular activity of noradrenaline in normotensive and genetically hypertensive rats.

“…Chronotropic responses of isolated, paired atria to intramural adrenergic nerve stimulation were studied by the method reported in a previous paper (Bell & Grabsch, 1976). 5 sec trains of 0-5 msec monophasic square-wave pulses were delivered at frequencies of 1 and 5 Hz and supramaximal voltage.…”

“…In view of the apparent absence of involvement of Uptake2 in terminating vascular responses to catecholamines we examined responses to adrenergic nerve stimulation of isolated atria, where Uptake2 has been shown previously to be concerned in termination of the response (Bell & Grabsch, 1976 DMI by Bell & Grabsch (1976) (Fig. 4) (Fig.…”