5-HYDROXYTRYPTAMINE 5-HT1B RECEPTORS INHIBITING CYCLIC-AMP ACCUMULATION IN RAT RENAL MESANGIAL CELLS

A clonal cell line derived from rat renal mesangial cells was shown to express endogenous 5-hydroxy-tryptamine (serotonin, 5-HT) receptors t hat mediate inhibition of cyclic AMP accumulation. These receptors wer e characterized as being of the 5-HT1B receptor subtype. 5-HT1 recepto r agonists inhibited forskolin-stimulated cyclic AMP accumulation in r at renal mesangial cells (60-70% maximal inhibition) with the followin g rank order of potency (mean pEC(50) values+/-SEM, n greater than or equal to 3): ergotamine (9.58+/-0.51)>RU 24969 (8.67+/-0.23)greater th an or equal to 5-CT (8.42+/-0.06)greater than or equal to CP 93129 (8. 15+/-0.27)>5-HT (7.75+/-0.11)>sumatriptan (6.29+/-0.30)>8-OH-DPAT (4.3 2+/-0.15). 5-HT2 and 5-HT4 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 part ial agonist (27% maximal inhibition, pEC(50) 7.19+/-0.24, n = 3); when used as an antagonist at 1 mu M, it shifted the concentration-respons e curve of 5-HT to the right (pK(B) 7.22+/-0.35, n = 3). Methiothepin was a competitive antagonist of 5-HT (pA(2) 8.04+/-0.10, Schild slope 0.87+/-0.21, n = 3). Rauwolscine (10 mu M) had no antagonist activity. There was a significant correlation (r = 0.98, P = 0.0001) between th e cyclic AMP data obtained in rat mesangial cells and 5-HT1B binding d ata reported in rat brain cortex. The same pattern of responses was ob served in early passages of primary cultures of rat mesangial cells. T his study shows that rat mesangial cells can be used as a convenient s ource of functional 5-HT1B receptors. It also constitutes further evid ence for the widespread distribution of 5-HT1B receptors outside the b rain.