THE EFFECT OF -TM 10 ON THE PHARMACOLOGICAL, BIOCHEMICAL AND MORPHOLOGICAL CHANGES INDUCED BY DENERVATION OF THE NICTITATING MEMBRANE OF THE CAT

S. PLUCHINO ¹, L. S. VAN ORDEN III ¹, P. R. DRASKCZY ¹, S. Z. LANGER ¹, and U. TRENDELENBURG ¹

¹ Department of Pharmacology, Harvard Medical School, Boston, Massachusetts; Oakdale Toxicology Center, Department of Pharmacology, University of Iowa, Oakdale, Iowa

About 24 hours after denervation, the nictitating membrane of the conscious cat contracts transiently for several hours, probably because of leakage of transmitter from degenerating adrenergic nerve endings. Injected when the degeneration contraction was half developed, -TM 10 (10 mg/kg s.c.) had the following effects. The degeneration contraction was shortened and, after an interval of 6 to 10 hours, it was followed by a second contraction. During the interval of quiescence between the two contractions, the gradual decline in the norepinephrine content of the denervated membrane was arrested, as was the decline in granular vesicles observed on electron micrographs of adrenergic nerve endings. The delay in the decline of the catecholamine fluorescence of adrenergic nerves was even more pronounced. This is compatible with a shift of the endogenous norepinephrine from vesicular to extravesicular compartments. It is likely that the observed inhibition of monoamine oxidase accounts for this phenomenon. On the other hand, -TM 10 altered neither the time course of the degeneration of adrenergic fibers nor that of the development of denervation supersensitivity to l-norepinephrine. Hence, the evidence is compatible with the view that the two latter phenomena are causally related.