THE NOREPINEPHRINE STORES OF ISOLATED ATRIA OF GUINEA PIGS PRETREATED WITH RESERPINE

¹ Department of Pharmacology, Harvard Medical School, Boston, Massachusetts

Isolated atria obtained from guinea pigs pretreated with reserpine (5 mg/kg given intraperitoneally 24 hours prior to the experiment) were exposed to norepinephrime. Forty-five minutes after the removal of the norepinephrine from the bath the response of the atrial pacemaker to tyramine was restored; direct measurements of the uptake of di-H³- norepinephrine demonstrated that a significant amount of radioactive norepinephrine was taken up into the organ. The uptake was small, and the response was easily exhausted by repeated administration of tyramine. Exposure to norepinephrine also restored the response of the atrial pacemaker to other sympathomimetic amines with indirect action. The optimal conditions for this partial refilling of previously depleted stores have been defined.

Of various sympathomimetic amines, only norepinephrine and epinephrine were able to restore the response to tyramine at 30°C. Dopamine was effective only at 37°C, although the increase in temperature did not enhance the restorative effect of norepinephrine.

Cocaine and various sympathomimetic amines (of direct, indirect or mixed action) antagonized the restoration of the response to tyramine when they were present during the period of exposure to norepinephrine. Experiments with radioactive norepinephrine demonstrated that this antagonism was due to a prevention of uptake of norepinephrine.

The results indicate that during the refilling, norepinephrine enters a small compartment of the store, and that tyramine releases norepinephrine from this compartment. The results are compatible with the view that all sympathomimetic amines may be taken up into the stores, and that all of them may inhibit the uptake of norepinephrine. Sympathomimetic amines appear to have certain actions common to all of them, and they appear to differ quantitatively rather than qualitatively from each other.