Photoreceptors of mouse retinas possess D4 receptors coupled to adenylate cyclase.
In the mouse, the light-sensitive pool of cAMP can be eliminated in the dark by application of the dopamine D2-like receptor agonists LY 171555 (quinpirole), (+)-N0437 (2-[N-(n-propyl)-N-2-(thienylethylamino)-5-hydroxytetralin]) , or (+)-3-PPP [3-(3-hydroxyphenyl)-N-propylpiperidine hydrochloride]. The rank-order affinity of the ability of the D2-like antagonists to block the action of LY 171555 matched that of the rat D4 receptor. Reverse transcription of retina mRNA followed by DNA amplification using D4-specific nucleotides demonstrates the presence of D4 mRNA in retina. In situ hybridization studies using D4-specific digoxygenin-labeled oligonucleotides or 35S-labeled UTP RNA probes demonstrate the presence of D4 mRNA in the photoreceptor cell layer and in the inner nuclear and ganglion cell layers. The modulation by D4 ligands of the dark level of light-sensitive cAMP in photoreceptors demonstrates the physiological coupling of the D4 receptor subtype.
Cohen
A I
AI
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110.
Todd
R D
RD
Harmon
S
S
O'Malley
K L
KL
D000262:Adenylyl Cyclases / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D001549:Benzamides / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004873:Ergolines / Q000494:pharmacology; D015870:Gene Expression; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D019257:Quinpirole; D012333:RNA, Messenger / Q000235:genetics; D011954:Receptors, Dopamine / Q000235:genetics / Q000502:physiology*; D012160:Retina / Q000502:physiology*; D013134:Spiperone / Q000494:pharmacology
D001549:Benzamides; D004873:Ergolines; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D019257:Quinpirole; D013134:Spiperone; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D003024:Clozapine; C030265:nemonapride