Partial agonism at serotonin 5-HT1B and dopamine D-2L receptors using a luciferase reporter gene assay

We have used a luciferase reporter gene assay to study the functional respo nses of two G-protein-coupled receptors in Chinese hamster ovary (CHO) cell s. The rank order of potency of drugs for the endogenous 5-HT1B receptor wa s 5-Hydroxytryptamine (5-HT)> zolmitriptan > dihydroergocristine >(-)Lisuri de (with no response to bromocriptine), However, only 5-HT and (-)lisuride produced a full functional response, with zolmitriptan and dihydroergocrist ine achieving 69 +/- 2% and 50 +/- 1% of the maximal response. In the same cells stably transfected with the rat dopamine D-2L receptor, dopamine and bromocriptine produced a full agonist functional response, whilst (-)lisuri de produced a biphasic response curve, indicating activity at both the endo genous 5-HT1B and exogenous dopamine D-2L receptors. Using the receptor spe cific antagonists, pindolol and(+)butaclamol, (-)lisuride was shown to prod uce 52% of the maximal response at the dopamine D-2 receptor relative to do pamine. In comparison to a cAMP accumulation assay, the rank orders of pote ncy and intrinsic activity were the same for all compounds used. These resu lts demonstrate that this reporter gene assay is capable of discriminating both potency and efficacy of drugs and can be used to characterise partial agonists at endogenously and heterologously expressed receptors in CHO cell s. (C) 1999 Elsevier Science B.V. All rights reserved.