Differential induction of adenylyl cyclase supersensitivity by antiparkinson drugs acting as agonists at dopamine D-1/D-2/D-3 receptors vs D-2/D-3 receptors only: Parallel observations from co-transfected human and native cerebral receptors

作者：Aloisi Gabriella; Silvano Elena; Rossi Mario; Millan Mark J; Maggio Roberto^*

来源：Neuropharmacology, 2011, 60(2-3): 439-445.

DOI：10.1016/j.neuropharm.2010.10.018

• Dopamine receptor
• Heterodimer
• Heteromerization
• Adenylyl cyclase
• Supersensitivity
• Gambling

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.

• 出版日期2011-3