Levodopa but not ropinirole induces an internalization of D1 dopamine receptors in parkinsonian rats.
Levodopa therapy in Parkinson's disease is mediated by dopamine receptors and, in a recent study, we showed that a Dl full agonist can induce an internalization of D1 dopamine receptors. The aim of the present study was to determine whether levodopa or a dopamine agonist such as ropinirole can also induce the internalization of D1 dopamine receptors in the striatum of control and hemiparkinsonian rats. The distribution of D1 dopamine receptors was analyzed by immunohistochemistry using a specific antibody. In control animals and 6-hydroxydopamine (6-OHDA)-lesioned animals treated with saline, D1 dopamine receptors were localized at the level of the plasma membrane. In contrast, in both lesioned and nonlesioned animals receiving a single dose of levodopa, but not in animals receiving ropinirole, D1 dopamine receptors were internalized in the cytoplasm. This result is likely explained by the fact that ropinirole binds to non-D1 dopamine receptors, whereas levodopa, which increases dopamine levels, indirectly acts on both D1 and D2 receptors. Ropinirole is consequently less likely to desensitize D1 dopamine receptors than levodopa and, thus, to reduce the efficacy of the treatment.
Muriel
Marie-Paule
MP
Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la salpêtrière, Paris, France.
Orieux
Gaël
G
Hirsch
Etienne C
EC
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D002230:Carbidopa / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology; D003593:Cytoplasm / Q000187:drug effects* / Q000473:pathology; D004338:Drug Combinations; D007211:Indoles / Q000494:pharmacology*; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D016253:Microscopy, Immunoelectron; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects*; D013570:Synaptic Membranes / Q000187:drug effects* / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000978:Antiparkinson Agents; D004338:Drug Combinations; D007211:Indoles; D017447:Receptors, Dopamine D1; C009265:carbidopa, levodopa drug combination; C046649:ropinirole; D007980:Levodopa; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D002230:Carbidopa