Differential induction of adenylyl cyclase supersensitivity by antiparkinson drugs acting as agonists at dopamine D1/D2/D3 receptors vs D2/D3 receptors only: parallel observations from co-transfected human and native cerebral receptors.

Abstract

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.

• Authors: Gabriella Aloisi, Elena Silvano, Mario Rossi, Mark J Millan, Roberto Maggio
• Journal: Neuropharmacology (Neuropharmacology) 2011 Feb-Mar Vol. 60 Issue 2-3 Pg. 439-45 ISSN: 1873-7064 [Electronic] England
• PMID: 21035472 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Antiparkinson Agents
• Dopamine Agonists
• Receptors, Dopamine D1
• Receptors, Dopamine D2
• Receptors, Dopamine D3
• Adenylyl Cyclases

Topics

• Adenylyl Cyclases (biosynthesis)
• Animals
• Antiparkinson Agents (pharmacology, therapeutic use)
• CHO Cells
• Cerebral Cortex (drug effects, enzymology)
• Cricetinae
• Cricetulus
• Dopamine Agonists (pharmacology, therapeutic use)
• Enzyme Induction (drug effects, physiology)
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Parkinson Disease (enzymology)
• Receptors, Dopamine D1 (agonists, metabolism)
• Receptors, Dopamine D2 (agonists, metabolism)
• Receptors, Dopamine D3 (agonists, metabolism)
• Transfection (methods)