The release of acetylcholinesterase in vivo is regulated by dopaminergic systems in the guinea-pig substantia nigra.
Acetylcholinesterase (AChE) and dopamine are both stored and released from dendrites within the substantia nigra: however, it is as yet unknown whether the regulation of these two purported neuromodulators is in any way related. Using a sensitive chemiluminescent system to monitor AChE release 'on-line', the effects of inhibiting synthesis and storage of dopamine with alpha-methyl-p-tyrosine (AMPT: 250 mg/kg, i.p.) and reserpine (6 mg/kg, i.p.), respectively, have been studied. Both these agents significantly reduced nigral tissue dopamine levels by decreases of 83% and 63%, respectively; however, only AMPT had a significant effect in vivo on the spontaneous release of AChE compared to conscious control animals (66% decrease). Co-application of both AMPT and reserpine resulted in a significant decrease in the tissue dopamine content (95%) and in spontaneous release of AChE compared to conscious control guinea-pigs (72%); however, these effects were not significantly different from when AMPT was employed alone. Application of potassium ions (60 mM) or veratridine (100 microM) both evoked release of AChE in control animals: however, when expressed as a percentage of basal levels, this increase in release was not influenced by drug treatment or state of consciousness. These results suggest that de novo dopamine synthesis may at least in part, have an influential effect on release (and possibly storage) of AChE in the substantia nigra.
Dally
J J
JJ
University Department of Pharmacology, Oxford, U.K.
Greenfield
S A
SA
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D006168:Guinea Pigs; D008163:Luminescent Measurements; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D019805:alpha-Methyltyrosine
D018492:Dopamine Antagonists; D008781:Methyltyrosines; D019805:alpha-Methyltyrosine; D012110:Reserpine; D000110:Acetylcholinesterase; D011188:Potassium; D004298:Dopamine