Cloning, expression and pharmacology of the mouse 5‐HT4L receptor

Abstract

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.