Salvatore C A, Woyden C J, Guidotti M T, Pettibone D J, Jacobson M A
Merck Research Laboratories, Department of Pharmacology, West Point, PA 19486, USA.
J Recept Signal Transduct Res. 1998 Jan;18(1):15-24. doi: 10.3109/10799899809039162.
The oxytocin receptor belongs to the family of G-protein-coupled receptors (GPCRs) characterized by seven transmembrane spanning domains and mediates numerous neurotransmitter and hormonal functions. The cloning of this receptor was initiated to validate the use of the rhesus monkey (Macaca mulatta) as a viable animal model for therapeutic development of oxytocin receptor antagonists by ruling out potential species variations that are sometimes present among GPCRs. The rhesus monkey oxytocin receptor was cloned by the polymerase chain reaction (PCR) and expressed transiently in 293/EBNA cells. The cDNA encodes a protein of 389 amino acids and is highly homologous to that from other species, especially the human receptor which exhibits 97% identity to the rhesus protein. The cloned receptor shows a very similar pharmacological profile to the human oxytocin receptor for a variety of agonists and antagonists from various structural classes. These results substantiate the validity of the rhesus monkey as a useful model for the evaluation of human therapeutics.
催产素受体属于G蛋白偶联受体（GPCRs）家族，其特征为具有七个跨膜结构域，并介导多种神经递质和激素功能。启动该受体的克隆是为了通过排除GPCRs中有时存在的潜在物种差异，验证恒河猴（猕猴）作为催产素受体拮抗剂治疗开发的可行动物模型。通过聚合酶链反应（PCR）克隆了恒河猴催产素受体，并在293/EBNA细胞中瞬时表达。该cDNA编码一个由389个氨基酸组成的蛋白质，与其他物种的蛋白质高度同源，尤其是与恒河猴蛋白质具有97%同一性的人类受体。对于来自各种结构类别的多种激动剂和拮抗剂，克隆的受体显示出与人类催产素受体非常相似的药理学特征。这些结果证实了恒河猴作为评估人类治疗药物有用模型的有效性。
