1 RT ± PCR technique was used to clone the human 5-HT 4(e) receptor (h5-HT 4(e) ) from heart atrium. We showed that this h5-HT 4(e) receptor splice variant is restricted to brain and heart atrium. 2 Recombinant h5-HT 4(e) receptor was stably expressed in CHO and C6-glial cell lines at 347 and 88 fmol mg 71 protein, respectively. Expression of h5-HT 4(e) receptors at the cell membrane was con®rmed by immunoblotting. 3 The receptor binding pro®le, determined by competition with [3 H]-GR113808 of a number of 5-HT 4 ligands, was consistent with that previously reported for other 5-HT 4 receptor isoforms. Surprisingly, we found that the rank order of potencies (EC 50 ) of 5-HT 4 agonists obtained from adenylyl cyclase functional assays was inversely correlated to their rank order of anities (K i ) obtained from binding assays. Furthermore, EC 50 values for 5-HT, renzapride and cisapride were 2 fold lower in C6-glial cells than in CHO cells. 4 ML10302 and renzapride behaved like partial agonists on the h5-HT 4(e) receptor. These results are in agreement with the reported low ecacy of the these two compounds on L-type Ca 2+ currents and myocyte contractility in human atrium. 5 A constitutive activity of the h5-HT 4(e) receptor was observed in CHO cells in the absence of any 5-HT 4 ligand and two 5-HT 4 antagonists, GR113808 and ML10375, behaved as inverse agonists. 6 These data show that the h5-HT 4(e) receptor has a pharmacological pro®le which is close to the native h5-HT 4 receptor in human atrium with a functional potency which is dependent on the cellular context in which the receptor is expressed.

The active form of human immunodeficiency virus type 1 protease (HIV-1 PR) is a homodimeric structure in which two subunits are linked through a two-stranded antiparallel beta-sheet consisting of the N- and C-termini of each monomer. To inhibit the dimerization process or disrupt the dimeric interface leading to inactive enzyme, conformationally constrained "molecular tongs" have been designed and synthesized to interfere with one monomer end in a beta-sheet fashion. These molecules are based on two peptidic strands attached to an aromatic scaffold. Inhibitions (submicromolar range) were obtained with molecular tongs containing tripeptidic or tetrapeptidic arms attached to a pyridinediol- or naphthalenediol-based scaffold (Kid = 0.56-4.5 microM at pH 4.7 and 30 degrees C). Kinetic studies are in agreement with an interface inhibition mechanism.