TIME COURSE OF THE DEVELOPMENT OF SUPERSENSITIVITY TO VARIOUS AMINES IN THE NICTITATING MEMBRANE OF THE PITHED CAT AFTER DENERVATION OR DECENTRALIZATION

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

The denervated or decentralized nictitating membrane of the pithed cat has little or no tone. Hence, accurate determinations of supersensitivity can be obtained. In pithed cats denervation and decentralization caused much more supersensitivity than previously observed in spinal cats (which have tone because of high plasma levels of catcholamines). Furthermore, both types of supersensitivity increase for up to 28 days after the operation; previous observations in spinal cats indicated that maximal supersensitivity was reached after 2 weeks. Although the new results differ quantitatively from older ones obtained in spinal cats, they are fully consistent with previous postulates concerning the mechanisms involved in supersensitivity. They are consistent with the view that denervation supersensitivity has a cocaine-like, presynaptic component which develops rapidly during the 2nd postoperative day when the adrenergic nerve terminals degenerate, and a decentralization -like, postsynaptic component which develops slowly and gradually for at least 4 weeks after the operation. The evidence supports the view that these two types of supersensitivity differ qualitatively. Evidence was also obtained for the view that postganglionic nerve stimulation causes a greater release of norepinephrine from decentralized than from normal nerve terminals.