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

The relation between the noradrenaline content of isolated guinea-pig atria and the rate-increasing action of tyramine was studied by the use of pretreatment with reserpine as a pharmacological tool for graded depletion of the noradrenaline stores. Reserpine was more potent in depleting the stores than in reducing the biological response to tyramine; 50% depletion had little effect on the response to tyramine; 50% reduction of the response to tyramine occurred when the noradrenaline content fell to about 10% of normal. Depletion of the stores of guinea-pig atria did not result in supersensitivity to noradrenaline. Exposure of heavily pretreated atria to 3 x 10(-6) noradrenaline for 10 min (followed by repeated washing for 45 min) restored the response to tyramine to 70% of normal; it failed, however, to restore the noradrenaline content to the level expected from the experiments with reserpine alone. Restoration of the response to tyramine was accompanied by a small but significant increase in the noradrenaline content of the atria; a change in sensitivity to added noradrenaline did not occur. The results are consistent with the view that (a) the noradrenaline stores consist of two compartments the smaller of which is important for the action of tyramine, that (b) this smaller compartment can be at least partially refilled by exposure of the atria to noradrenaline, and that (c) there is no direct relationship between the noradrenaline content and the sensitivity to noradrenaline in guinea-pig atria.