A new approach to finding specific dopamine D4 receptor agonists.

This paper describes a new approach to finding specific dopamine D4 receptor agonists based on pharmacological analysis of the contractile response to ATP in guinea pig vas deferens. A partial cDNA of the dopamine D4 receptor of the vas deferens was identified. In the vas deferens, reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis revealed the existence of dopamine D4 receptor mRNA and D4 receptor protein, respectively. ATP (10(-7) M) induced a transient phasic contraction in the presence of prazosin (10(-7) M), an alpha1-adrenoceptor antagonist. This contraction was potentiated by dopamine receptor agonists in a concentration-dependent manner; and was antagonized by 8-Methyl-6-(4-methyl-1-piperazinyl)-11H-pyrido[2,3-b][1,4]benzodiazepine (JL-18), a dopamine D4 receptor antagonist, but not by raclopride, a dopamine D2 and D3 receptor antagonist. Assay methods utilizing contractile responses to ATP may be available for identifying novel dopamine D4 receptor agonists.