Claeysen S, Sebben M, Journot L, Bockaert J, Dumuis A
CNRS UPR 9023, Centre CNRS-INSERM de Pharmacologie-Endocrinologie (CCIPE), Montpellier, France.
FEBS Lett. 1996 Nov 25;398(1):19-25. doi: 10.1016/s0014-5793(96)01132-5.
Since most of our knowledge on pharmacological properties of brain 5-HT4 receptors have been discussed for mouse colliculi neurons, we cloned the corresponding receptor using the RT-PCR approach. As expected, the homology with the already cloned rat 5-HT(4L) receptor was high, revealing only 16 differences at the amino-acid level. One of the differences, proline75 in mouse, alanine75 in the already published rat sequences was not confirmed. Therefore this proline is part of the consensus sequence present in all 5-HT receptor transmembrane domain II (LVMP). Comparing the affinities of 11 agonists and five antagonists for the cloned mouse receptor (5-HT(4L))expressed in LLCPK1 and the corresponding receptor in mouse colliculi shows an excellent correlation. The transfected mouse 5-HT(4L) receptor stimulated cAMP production. When expressed at high density, it exhibited intrinsic activity. In contrast to the previously described distribution, we found that mRNA encoding for both the short (5-HT(4S))and the long form (5-HT(4L)) of 5-HT4 receptors are expressed in all mouse and rat brain areas.
由于我们关于脑5-羟色胺4（5-HT4）受体药理学特性的大部分知识都是针对小鼠上丘神经元进行讨论的，我们采用逆转录-聚合酶链反应（RT-PCR）方法克隆了相应的受体。正如预期的那样，它与已克隆的大鼠5-HT(4L)受体的同源性很高，在氨基酸水平上仅显示出16处差异。其中一个差异，即小鼠中的脯氨酸75，在已发表的大鼠序列中为丙氨酸75，未得到证实。因此，该脯氨酸是所有5-HT受体跨膜结构域II（LVMP）中共有序列的一部分。比较11种激动剂和5种拮抗剂对在LLCPK1中表达的克隆小鼠受体（5-HT(4L)）和小鼠上丘中相应受体的亲和力，结果显示出极好的相关性。转染的小鼠5-HT(4L)受体刺激了环磷酸腺苷（cAMP）的产生。当高密度表达时，它表现出内在活性。与先前描述的分布情况相反，我们发现编码5-HT4受体短形式（5-HT(4S)）和长形式（5-HT(4L)）的信使核糖核酸（mRNA）在所有小鼠和大鼠脑区均有表达。
