Modulation of Intracellular Cyclic AMP Levels by Different Human Dopamine D4 Receptor Variants
Article first published online: 23 NOV 2002
Journal of Neurochemistry
Volume 65, Issue 3, pages 1157–1165, September 1995
How to Cite
Asghari, V., Sanyal, S., Buchwaldt, S., Paterson, A., Jovanovic, V. and Van Tol, H. H. M. (1995), Modulation of Intracellular Cyclic AMP Levels by Different Human Dopamine D4 Receptor Variants. Journal of Neurochemistry, 65: 1157–1165. doi: 10.1046/j.1471-4159.1995.65031157.x
- Issue published online: 23 NOV 2002
- Article first published online: 23 NOV 2002
- Received January 19, 1995; revised manuscript received March 28, 1995; accepted April 3, 1995.
- Dopamine receptors;
- Cyclic AMP;
Abstract: To investigate whether polymorphic forms of the human dopamine D4 receptor have different functional characteristics, we have stably expressed cDNAs of the D4.2, D4.4, and D4.7 isoforms in several cell lines. Chinese hamster ovary CHO-K1 cell lines expressing D4 receptor variants displayed pharmacological profiles that were in close agreement with previous data from transiently expressed D4 receptors in COS-7 cells. Dopamine stimulation of the D4 receptors resulted in a concentration-dependent inhibition of the forskolin-stimulated cyclic AMP (cAMP) levels. The potency of dopamine to inhibit cAMP formation was about twofold reduced for D4.7 (EC50 of ∼37 nM) compared with the D4.2 and D4.4 variants (EC50 of ∼16 nM). Antagonists block the dopamine-mediated inhibition of cAMP formation with a rank order of potency of emonapride > haloperidol = clozapine ≫ raclopride. There was no obvious correlation between the efficacy of inhibition of forskolin-stimulated cAMP levels and the D4 subtypes. Dopamine could completely reverse prostaglandin E2-stimulated cAMP levels for all three D4 receptor variants. Deletion of the repeat sequence does not affect functional activity of the receptor. The data presented indicate that the polymorphic repeat sequence causes only small changes in the ability of the D4 receptor to block cAMP production in CHO cells.