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.
Morishita
Hideji
H
Department of Pharmacology, School of Medicine, Fukuoka University, Fukuoka 814-0180, Japan. m-hideji@fukuoka-u.ac.jp
Shibata
Kazuhiko
K
Sakata
Noriyuki
N
Kita
Satomi
S
Katsuragi
Takeshi
T
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015153:Blotting, Western; D001971:Bromocriptine / Q000494:pharmacology; D003001:Cloning, Molecular; D003024:Clozapine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D010627:Phenethylamines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D050638:Receptors, Dopamine D4; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014649:Vas Deferens / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
C425777:10,11-dihydroxy-N-n-propylnorapomorphine; D000317:Adrenergic alpha-Antagonists; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D010627:Phenethylamines; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; C093454:JL 18; D019257:Quinpirole; D001971:Bromocriptine; C041369:2-(N-phenethyl-N-propyl)amino-5-hydroxytetralin; D000255:Adenosine Triphosphate; D003024:Clozapine; D001058:Apomorphine; D004298:Dopamine; D011224:Prazosin