PT  - JOURNAL ARTICLE
AU  - J. B. FURNESS
AU  - G. R. CAMPBELL
AU  - S. M. GILLARD
AU  - T. MALMFORS
AU  - J. L.S. COBB
AU  - G. BURNSTOCK
TI  - CELLULAR STUDIES OF SYMPATHETIC DENERVATION PRODUCED BY 6-HYDROXYDOPAMINE IN THE VAS DEFERENS
DP  - 1970 Jul 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 111--122
VI  - 174
IP  - 1
4099  - http://jpet.aspetjournals.org/content/174/1/111.short
4100  - http://jpet.aspetjournals.org/content/174/1/111.full
SO  - J Pharmacol Exp Ther1970 Jul 01; 174
AB  - The effect of 6-hydroxydopamine (6-OHDA) on the ultrastructure, fluorescent histochemistry, electrophysiology and pharmacology of the mouse and rat vas deferens has been examined during the first 24 hours after single intravenous injections. During the first hour there was a marked increase in the granulation of the intra-axonal vesicles, spontaneous contractions occurred, and there was an increase in the frequency of spontaneous junction potentials. These results indicate the displacement, by 6-OHDA, of discrete packets of noradrenaline from intra-axonal stores. By 4 to 6 hours, there was a general decrease in the fluorescent intensity of adrenergic nerves. At 24 hours the fluorescent intensity of the nerves had returned to about normal, but there was a dose-dependent decrease in the number of nerves. The first sign of axon damage was seen at 1 to 2 hours, consisting of a general electron transparency of the axoplasm and a decrease in the number of axonal inclusions. Some of the axons recover from this type of damage. At 2 to 10 hours after injection of 6-OHDA, axons with a general darkening of the axoplasm were observed. This damage has been termed primary degeneration and is apparently not reversible. It is reminiscent of the appearance of axons after surgical denervation. Neuromuscular transmission failed 2 to 7 hours after the injection of 6-OHDA, depending on the conditions of the experiment. The mechanism of action of 6-OHDA on adrenergic nerves is discussed. It is concluded that nerve degeneration occurs when a critical concentration of 6-OHDA is reached in the axoplasm. Damage to the membrane potentiates the packaged release of noradrenaline. ALthough entry of 6-OHDA into granular vesicles occurs, it does not appear to be essential for degeneration. © 1970, by The Williams & Wilkins Company