Swelling of the small adrenergic storage vesicles and the loss of vesicular ATP induced by cocaine in the isolated rat tail artery.
Exposure of the isolated rat tail artery to cocaine (greater than 0.03 mmol/l) was found to cause release of noradrenaline from the small (40 nm) storage vesicles in adrenergic varicosities (Palatý 1988). In the present study transmission electron microscopy was used to determine whether or not cocaine also affects the volume and the ATP content of the vesicles in situ. 1. Evaluation of electron micrographs of arterial segments fixed in a buffered mixture of paraformaldehyde and glutaraldehyde showed that cocaine (3 mmol/l; 15 min) caused significant, though non-uniform, swelling of the small vesicles. 2. To confirm the selectivity of the uranaffin method of ATP localization with respect to noradrenaline, the latter was depleted by prior injection of the rats with reserpine. As a result the fraction of the small vesicles containing electron-dense cores decreased from 55% in control specimens to 29%. 3. In the specimens processed by the uranaffin method, cocaine (3 mmol/l; 30 min) lowered the fraction of the vesicles containing electron-dense cores by about 80%. 4. After having been lowered by cocaine, the fractions of vesicles containing electron-dense cores in specimens processed by the chromaffin and uranaffin methods were restored during incubation of the tissue in cocaine-free medium supplemented with dopamine (7 mumol/l) and L-ascorbate (0.3 mmol/l). There was no restoration of the cores in the specimens processed by the uranaffin method when the tissue had been incubated in the absence of dopamine. 5. These observations support the hypothesis that unprotonated cocaine diffuses into and accumulates in the small vesicles in situ. They also suggest that, as in chromaffin granules (Caughey and Kirshner 1987), interaction of ATP and noradrenaline may be essential for effective storage of the nucleotide in the small vesicles.
Palatý
V
V
Department of Anatomy, University of British Columbia, Vancouver, Canada.
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001158:Arteries / Q000294:innervation; D003042:Cocaine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D013623:Tail / Q000098:blood supply
D012110:Reserpine; D000255:Adenosine Triphosphate; D003042:Cocaine