5-Hydroxytryptamine 5-HT receptors inhibiting cyclic AMP accumulation in rat renal mesangial cells.

Autor: Schoeffter, P., Pfeilschifter, J., Bobirnac, I.
Zdroj: Naunyn-Schmiedeberg's Archives of Pharmacology; 1995, Vol. 351 Issue 1, p35-39, 5p
Abstrakt: A clonal cell line derived from rat renal mesangial cells was shown to express endogenous 5-hydroxytryptamine (serotonin, 5-HT) receptors that mediate inhibition of cyclic AMP accumulation. These receptors were characterized as being of the 5-HT receptor subtype. 5-HT receptor agonists inhibited forskolin-stimulated cyclic AMP accumulation in rat renal mesangial cells (60-70% maximal inhibition) with the following rank order of potency (mean pEC values±SEM, n ≥ 3): ergotamine (9.58±0.51)>RU 24969 (8.67±0.23)≥5-CT (8.42±0.06)≥CP 93129 (8.15±0.27)>5-HT (7.75±0.11) > sumatriptan (6.29±0.30) > 8-OH-DPAT (4.32±0.15). 5-HT and 5-HT receptor agonists were without effect. 5-HT-induced inhibition of cyclic AMP accumulation was abolished by a pre-treatment of the cells with pertussis toxin. (-)Propranolol was a partial agonist (27% maximal inhibition, pEC 7.19±0.24, n = 3); when used as an antagonist at 1 μM, it shifted the concentration-response curve of 5-HT to the right (pKB 7.22±0.35, n = 3). Methiothepin was a competitive antagonist of 5-HT (pA 8.04±0.10, Schild slope 0.87±0.21, n = 3). Rauwolscine (10 μM) had no antagonist activity. There was a significant correlation ( r = 0.98, P = 0.0001) between the cyclic AMP data obtained in rat mesangial cells and 5-HT binding data reported in rat brain cortex. The same pattern of responses was observed in early passages of primary cultures of rat mesangial cells. This study shows that rat mesangial cells can be used as a convenient source of functional 5-HT receptors. It also constitutes further evidence for the widespread distribution of 5-HT receptors outside the brain. [ABSTRACT FROM AUTHOR]
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