期刊
NEUROPHARMACOLOGY
卷 60, 期 2-3, 页码 439-445出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2010.10.018
关键词
Dopamine receptor; Heterodimer; Heteromerization; Adenylyl cyclase; Supersensitivity; Gambling
资金
- Fondo per gli Investimenti della Ricerca di Base (FIRB) [RBIN04CKYN]
- Progetti di ricerca di interesse nazionale (PRIN) [20085PPEK7]
- LIMPE (Lega Italiana per la lotta contro la malattia di Parkinson, le Sindromi Extrapiramidali e le Demenze)
- IDR Servier
Though there is evidence that sustained exposure of dopamine (DA) receptors to agonists can elicit a supersensitivity of adenylyl cyclase (AC), little is known about the pharmacological characteristics of this phenomenon, and possible interrelationships amongst DA receptor subtypes have not been examined. In cells co-transfected with D-1 plus D-2, or D-1 plus D-3, receptors, which are known to physically and functionally interact, long-term exposure to quinpirole, pramipexole and ropinirole (which possess negligible affinities for D-1 sites) elicited supersensitivity of D-1 receptor-activated AC. By contrast, D-2/D-3 receptor agonists that also act as D-1 receptor agonists, bromocriptine, lisuride, cabergoline, apomorphine and DA itself, did not elicit supersensitivity. Interestingly, AC supersensitivity was also observed in the nucleus accumbens of mice pretreated with twice-daily pramipexole and quinpirole, whereas no change was seen either with lisuride or with the DA precursor, L-DOPA. Thus, AC supersensitivity is elicited by the sustained exposure of cloned human and native mouse populations of dopaminergic receptors, to D-2/D-3 but not D-1/D-2/D-3 agonists. These observations may be related to the exacerbation of gambling in Parkinson's disease that is provoked by antiparkinson agents acting as selective D-2/D-3 receptor agonists, notably pramipexole. (C) 2010 Elsevier Ltd. All rights reserved.
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