Release of vesicular noradrenaline in the rat tail artery induced by cocaine.
The effects of cocaine on overflows of endogenous noradrenaline and DOPEG from isolated rat tail arteries were examined. 1. Both overflows increased progressively with increasing concentration of cocaine, while the (NA overflow)/(DOPEG overflow) ratio first increased and then decreased. The changes in the overflows induced by cocaine (0.1 mmol/l) appeared reversible. 2. Exposure of the tissue for 30 min to cocaine, 1 mmol/l, resulted in a significant decrease in the proportion of storage vesicles containing electron-dense cores. 3. The changes in overflows of noradrenaline and DOPEG induced by cocaine (0.1 mmol/l were unaffected by the presence of desipramine (0.1 mumol/l) or removal of extracellular Ca2+. The effect of cocaine on the overflow of noradrenaline was potentiated by prior inhibition of MAO with clorgyline. 4. Exposure of segments to a Ca2+-free, high K, low Na incubation medium was accompanied by increased overflow of noradrenaline. Cocaine (0.1 mmol/l) reduced the overflow of noradrenaline to about a half, and substantially increased the overflow of DOPEG. 5. The increase in the overflow of DOPEG from segments bathed in HEPES-buffered solutions, the pH of which ranged from 6.80 to 7.38, was approximately proportional to the calculated concentration of unprotonated (uncharged) cocaine. 6. Quantitatively similar changes in the overflows were observed when norcocaine was substituted for cocaine. Ecgonine methyl ester was much less potent than cocaine, and O-benzoyl ecgonine was ineffective. 7. The small increases in the overflow of noradrenaline observed at relatively low concentration (less than 30 mumol/l) of cocaine can be attributed primarily to inhibition of reuptake of the released transmitter by the cocaine- and desipramine-sensitive amine carrier.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Anatomy, University of British Columbia, Vancouver, Canada.
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002118:Calcium / Q000494:pharmacology; D003042:Cocaine / Q000031:analogs & derivatives / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D008854:Microscopy, Electron; D008995:Monoamine Oxidase / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013623:Tail / Q000098:blood supply*
C008671:norcocaine; D008734:Methoxyhydroxyphenylglycol; C005618:benzoylecgonine; C005617:ecgonine; D008995:Monoamine Oxidase; D003042:Cocaine; D002118:Calcium; D003891:Desipramine; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine