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Journal of Pharmacology And Experimental Therapeutics, Vol. 151, Issue 1, 73-86, 1966
Copyright © 1966 by American Society for Pharmacology and Experimental Therapeutics

THE ONSET OF DENERVATION SUPERSENSITIVITY

S. Z. Langer 1 and U. Trendelenburg 1

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

The time course of the development of supersensitivity to norepinephrine of the denervated nictitating membrane of the spinal cat was studied between the 16th and 40th hr after denervation of one side and decentralization of the other. Denervation supersensitivity was found to develop just before the degeneration contraction appeared; the former reached nearly maximal values after the latter had passed its maximum. Pretreatment with [2(2,6-dimethylphenoxy)propyl]trimethylammonium chloride monohydrate (beta-TM 10) delayed the onset of the degeneration contraction by about 10 hr, and correspondingly delayed the onset of denervation supersensitivity to norepinephrine. The maximum of the degeneration contraction was equivalent to one quarter of maximal shortening of the smooth muscle of the nictitating membrane. Evidence has been presented to show that such increases in tone reduce conventional estimates of supersensitivity. It has also been shown that tone can be determined quantitatively, and that estimates of supersensitivity can be corrected for tone. Dose-response curves for tyramine gave evidence that there is supersensitivity to this amine during the early stages of degeneration of the nerve terminals; tyramine was then found to be more effective than can be attributed to the supersensitivity to norepinephrine. In the later stages of degeneration, the maximal response to tyramine declined, probably because of the loss of norepinephrine from the stores. During early stages of the degeneration contraction there was spontaneous activity in the denervated nictitating membrane. The release of the transmitter during degeneration of adrenergic nerve terminals appears to be discontinuous.

Accepted on August 26, 1965




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Copyright © 1966 by the American Society for Pharmacology and Experimental Therapeutics.