1 Serotonin 5-HT 7 receptors are present in astrocytes. Understanding their role in this type of cell would greatly benefit from the identification of astroglial cell lines expressing this receptor type. 2 The aim of the present study was to assess the expression of native 5-HT 7 receptors and 5-HT 7 receptor mRNA in a number of human glioblastoma cell lines, by means of cAMP measurements, Western blot analysis and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis.

Human uterine artery smooth muscle cells in culture were shown to express constitutively both 5-ht7 receptor mRNA and 5-ht7-like receptors functionally linked to cyclic AMP formation. 5-Carboxamidotryptamine (5-CT) and 5-HT enhanced forskolin-stimulated cyclic AMP accumulation in these cells, with pEC50 values of 7.12 and 6.25, sumatriptan being very weakly active. Both methiothepin (0.1 gM) and clozapine (1 gM), but not the 5-HT4-receptor antagonist, SDZ 205-557 (10 gM) antagonized the effects of 5-CT. In reverse transcriptase-polymerase chain reaction analysis, the mRNA for 5-ht7, but not for 5-HT4 or 5-ht6 receptors was found to be strongly expressed in the same cells. These findings represent a further step toward the recognition of 5-ht7 receptors as real, functional receptors.

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1 The relationships between the density of dopamine D 4.4 receptors and the agonist e cacies of L-745,870 (3-(4-[4-chlorophhenyl]piperazin-1-yl)-methyl-1H-pyrrolo [2,3-b]pyridine) and U-101958 ((1-benzyl-piperidin-4-yl)-(3-isopropoxy-pyridin-2-yl)-methyl-amine) were investigated in Chinese hamster ovary (CHO) cells, after treatment with the gene expression enhancer, sodium butyrate. 2 In CHO cells expressing D 4.4 receptors (CHO/D 4 cells), dopamine inhibited forskolin-stimulated cyclic AMP accumulation (E max 56+1% inhibition, pEC 50 7.4+0.1, n=10). U-101958 behaved as a partial agonist (39+7% the e cacy of dopamine, pEC 50 8.1+0.3, n=4), whereas L-745,870 had no detectable agonist e ect. 3 Receptor density, as estimated by [ 3 H]-spiperone saturation binding was 240+30 fmol mg 71 protein (n=8) in CHO/D 4 cell homogenates. It reached 560+150 (n=6), 1000+190 (n=4) and 840+120 (n=4) fmol mg 71 protein after treatment with sodium butyrate (5 mM) for 6, 18 and 48 h, respectively. 4 The increase in receptor density was associated with a gradual enhancement of the agonist e ects (increased E max and pEC 50 values) of dopamine. The e cacy of U-101958 (relative to dopamine) doubled and L-745,870 was turned into a partial agonist (e cacy 49% relative to dopamine, pEC 50 8.6+0.2, n=6, after 48 h treatment with sodium butyrate). These agonist e ects of U-101958 and L-745,870 could be antagonized by spiperone (0.1 mM) but not by raclopride (10 mM). 5 The results show that U-101958 and L-745,870 are partial agonists at human dopamine D 4.4 receptors expressed in CHO cells. Their e cacy is governed by receptor density. Agonist e ects of these two compounds in vivo cannot be excluded under circumstances of increased receptor levels.

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