DISSOCIATION OF THE SUPERSENSITIVITY TO NOREPINEPHRINE CAUSED BY COCAINE FROM INHIBITION OF H³-NOREPINEPHRINE UPTAKE IN COLD STORED SMOOTH MUSCLE

¹ Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada

The relationship between the supersensitivity to norepinephrine caused by cocaine and inhibition of the uptake of H³-norepinephrine was studied in fresh and stored (6-8° C for 7 days) isolated smooth muscles. There was no significant difference between the sensitization (change in the ED50 of norepinephrine) produced by cocaine in fresh and stored rabbit aortic strips, in fresh and stored rabbit splenic strips or in fresh and stored cat nictitating membrane. Sensitization of the fresh rat vas deferens was significantly greater than that of the stored rat vas deferens. Cocaine increased the maximum effect of norepinephrine on fresh vas deferens but on none of the other preparations tested. Storage in the cold decreased the sensitivity of aortic strips to norepinephrine without changing their maxima, increased the sensitivity of splenic strips and vasa deferentia but decreased their maxima and did not change the sensitivity or maxima of nictitating membranes. Storage decreased the maximum response of aortic strips to potassium. The retention of H³-norepinephrine was taken as a measure of its uptake. It was found that the uptake of H³-norepinephrine by fresh aorta, spleen and vas deferens was significantly greater than that by corresponding stored preparations. Cocaine inhibited the uptake of H³-norepinephrine by fresh but not by stored preparations. Cocaine had no effect on the sensitivity of the fresh or the stored aortic strips to potassium. These data indicate that the supersensitivity caused by cocaine is not due to inhibition of uptake of norepinephrine in smooth muscles subjected to cold storage and that some postsynaptic action, possibly on adrenergic receptors, is responsible for the phenomenon of supersensitivity in these tissues.