Cohen A I, Todd R D, Harmon S, O'Malley K L
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110.
Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12093-7. doi: 10.1073/pnas.89.24.12093.
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.
在小鼠中，通过应用多巴胺D2样受体激动剂LY 171555（喹吡罗）、（+）-N0437（2-[N-（正丙基）-N-2-（噻吩基乙基氨基）-5-羟基四氢萘]）或（+）-3-PPP [3-（3-羟基苯基）-N-丙基哌啶盐酸盐]，可以在黑暗中消除光敏感的环磷酸腺苷（cAMP）池。D2样拮抗剂阻断LY 171555作用的能力的亲和力排序与大鼠D4受体的排序相匹配。视网膜mRNA的逆转录，随后使用D4特异性核苷酸进行DNA扩增，证明视网膜中存在D4 mRNA。使用D4特异性地高辛标记的寡核苷酸或35S标记的UTP RNA探针进行的原位杂交研究表明，感光细胞层以及内核层和神经节细胞层中存在D4 mRNA。感光细胞中光敏感cAMP暗水平受D4配体的调节，证明了D4受体亚型的生理偶联。
