SENSITIVITY OF THE NICTITATING MEMBRANE OF THE PITHED CAT TO INFUSIONS OF l-NOREPINEPHRINE AFTER DENERVATION OR DECENTRALIZATION

¹ Department of Pharmacology, The Merrell-National Laboratories, Division of Richardson-Merrell, Inc., Cincinnati, Ohio

The sensitivity of the nictitating membrane of the pithed cat to l-norepinephrine (NE), based on the measurement of steady-state responses to infusions of NE, was determined after denervation and decentralization. Denervation resulted in a parallel shift of the dose-response curve for NE to the left, while decentralization resulted in shifting it to the left with a decrease in slope. Both types of supersensitivity reached their maximum within seven days after operation and the maximum degrees of supersensitivity obtained were far smaller than those obtained previously in vivo with injections of NE but were close to those obtained in vitro. Since steady-state responses were determined in vitro and responses to injections of NE, which presumably represent the measurement of non-steady-state responses, were determined in vivo, the present results indicate that the differences in degrees of denervation and decentralization supersensitivity obtained previously in vivo with injections of NE and in vitro are due mainly, but not entirely, to the determination of the steady-state response in vitro and the non-steady-state response in vivo. Furthermore, the present results also demonstrate that the presence of spontaneous activity in the decentralized nictitating membrane may not only lead to overestimation of supensensitivity but also affects the time course of development of supersensitivity and the slope of dose-response curve for NE.