Apomorphine increases vesicular monoamine transporter-2 function: implications for neurodegeneration.
Apomorphine is a nonselective dopamine D1/D2 receptor agonist used in Europe to treat symptoms resulting from the dopaminergic degeneration associated with Parkinson's disease. In addition, neuroprotective effects of this agent in rodent models have been reported. Recent studies indicate that treatments that alter vesicular monoamine transporter-2 (VMAT-2) function may be protective in models of dopaminergic degeneration. Hence, the purpose of the present study was to examine the effect of apomorphine on VMAT-2 function. Results revealed that apomorphine rapidly and reversibly increased vesicular dopamine uptake, as determined in purified striatal vesicles obtained from treated rats. This increase occurred in both postnatal day 40 and postnatal day 90 rats, and was associated with a redistribution of VMAT-2 protein within nerve terminals. This effect of apomorphine on vesicular dopamine uptake was blocked by pretreating with eticlopride, a dopamine D2 receptor antagonist. The implications of these findings relevant to the treatment of neurodegeneration are discussed.
Truong
Jannine G
JG
Department of Pharmacology and Toxicology, University of Utah, 30 South 2000 East, Salt Lake City, UT 84112, USA.
Hanson
Glen R
GR
Fleckenstein
Annette E
AE
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001692:Biological Transport; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013572:Synaptic Vesicles / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D018491:Dopamine Agonists; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D001058:Apomorphine; D004298:Dopamine