THE INFLUENCE OF DENERVATION AND OF DECENTRALIZATION ON THE ALPHA AND BETA EFFECTS OF ISOPROTERENOL ON THE NICTITATING MEMBRANE OF THE PITHED CAT

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

After block of the beta receptors by propranolol, isoproterenol caused dose-dependent contractions of the normal nictitating membrane of the pithed cat through the activation of alpha receptors. Under these conditions, isoproterenol can be classified as a directly acting sympathomimetic amine. Two days after denervation, the sensitivity of the nictitating membrane to isoproterenol increased only 1.6-fold (as compared to a more than 10-fold increase to l-norepinephrine). Isolated, denervated nictitating membranes showed no supersensitivity to isoproterenol. However, 14 days after decentralization sensitivity to isoproterenol in the pithed cat had increased 5.5 times, a value not different from that for l-norepinephrine. These results are consistent with the view that the presynaptic type of denervation supersensitivity is restricted to those amines which are taken up by normal adrenergic nerve endings, whereas decentralization supersensitivity is of a qualitatively different type and of postsynaptic origin. The relaxant beta effects of isoproterenol were studied in normal and decentralized nictitating membranes which were in a state of partial contraction. At a time when there was a significant degree of decentralization supersensitivity to the alpha effects of isoproterenol, the inhibitory beta effects were unchanged. It is postulated that decentralization supersensitivity of the nictitating membrane is restricted to those agents which have excitatory actions.