Uptake of Labelled Noradrenaline by Isolated Atria

Abstract

The uptake of labelled noradrenaline by isolated rabbit atria has been studied, and the rate of outflow of radioactivity after a period of loading has been recorded. There is first a rapid outflow presumably from extracellular space, followed by a slow outflow presumably from intracellular space. Cocaine greatly diminished the intracellular uptake. Tyramine caused an increased outflow of radioactivity from intracellular sites which was not due to the increase in atrial rate, since noradrenaline which increased the rate more than tyramine had less effect on the outflow.In order to study the uptake of noradrenaline by isolated rabbit atria, observations have been made using noradrenaline containing '4C, which was sent to us by Dr. McChesney Goodall. The atria were prepared from rabbits of 1.5 to 2.0 kg body weight as described in the preceding paper by Azarnoff and Burn (1961). When the atria were set up in the bath for about 1 hr and were observed to be contracting normally, the labelled noradrenaline was added to the fluid in the bath and was allowed to act for-about 75 min. The bath was then emptied and the fluid was replaced and the rate of loss of radioactivity from the atria was determined. The effect of cocaine, of tyramine and of noradrenaline on this rate of outflow of radioactivity was observed. METHODSThe labelled noradrenaline was in solution in sealed glass ampoules and was (±)-[2-'4C] noradrenaline, the radioactivity being 9.5 ,C per ml. The concentration of DL-noradrenaline was 80.3 /ug per ml.In the various experiments the amounts of noradrenaline solution added to the 5 ml. bath varied from 0.1 to 0.3 ml. The noradrenaline was allowed to act for 75 min, after which time the bath was emptied. Five ml. of solution without noradrenaline was put in the bath and removed after 5 min. This procedure of emptying and filling the bath was repeated at varying intervals for 3 to 4 hr. All fluid removed from the bath was assayed for radioactivity by drying down a small aliquot on a planchette and counting in a windowless counter. No correction was made for self-absorption, the aliquot always having the same volume. At least 1,000 counts were recorded. RESULTSCourse of loss of radioactivity. The results in one experiment (Table 2, Expt. 13) were as follows. When the atria were set up in the bath at 320 C, they were beating

Effect of Tyramine on Isolated Guinea‐pig Atria in Relation to Their Noradrenaline Stores

“…However, supporting evidence from other experiments indicates that the postulated compartment A is of high functional importance. Radioactive noradrenaline is known to be taken up by normal tissues, from where it is released by tyramine (isolated rabbit atria, Burn & Burn, 1961) or by nerve stimulation (cat spleen, Hertting & Axelrod, 1961). After pretreatment with graded doses of reserpine, the reduction of the response to tyramine is significantly correlated with the reduction of the response to nerve stimulation (cat nictitating membrane, Trendelenburg, 1961).…”

The inactivation of infused noradrenaline by the cat spleen

“…Thus cocaine has been shown to prevent noradrenaline uptake in the heart, spleen and adrenals of the cat (Whitby et al 1960); so also in the rat heart and spleen, both in vivo (Muscholl, 1960(Muscholl, , 1961 and in vitro (Lindmar & Muscholl, 1963); and again in isolated rabbit atria (Burn & Burn, 1961) and in isolated slices of cortex, spleen or heart (Dengler, Spiegel & Titus, 1961). Phenoxybenzamine has been shown to block noradrenaline uptake in a variety of organs including the spleen of the cat (Hertting, A-xelrod & Whitby, 1961), in the heart and kidney in the rat (Farrant, Harvey & Pennefather, 1961) and in the cat spleen (Blakeley & Brown, 1963).…”

A Quantitative Study of the Effect of Cocaine on the Response of the Cat Nictitating Membrane to Nerve Stimulation and to Injected Noradrenaline

“…There is evidence that the noradrenaline-potentiating effect of cocaine is due to its ability to block the uptake of the amine by sympathetic nerve endings (Whitby, Hertting & Axelrod, 1960;Burn & Burn, 1961;Hertting, Axelrod & Patrick, 1961 ;Muscholl, 1961 ; Iversen & Whitby, 1962; Kopin, Hertting & Gordon, 1962;Wolfe, Potter, Richardson & Axelrod, 1962).…”