Pharmacological and molecular characterization of 5-hydroxytryptamine(7) receptors in the rat adrenal gland

Serotonin (5-hydroxytryptamine; 5-HT) is a potent stimulator of aldosterone secretion in the rat adrenal gland but the type of receptor involved in th e mechanism of action of 5-HT remains unknown. The aim of the present study was to determine the pharmacological profile and to clone the receptor res ponsible for the corticotropic effect of 5-HT in rat glomerulosa cells. A s eries of 10 serotonergic receptor agonists and 12 receptor antagonists was used to characterize the receptor mediating the effect of 5-HT on aldostero ne secretion from perifused rat adrenocortical slices. Correlation analysis between the potencies of the different compounds in our model and those pr eviously reported for various recombinant 5-HT receptors showed that the ra t adrenal 5-HT receptor exhibits the same pharmacological profile as the 5- HT, receptor transiently expressed in COS-7 cells (r = 0.82 for agonists, p < .05; r = 0.83 for antagonists, p < .01). Polymerase chain reaction with specific primers revealed the expression of 5-HT7 receptor mRNA in the rat adrenal gland. Cloning of the polymerase chain reaction product confirmed t hat the amplified DNA corresponded to the 5-HT7 receptor cDNA sequence. Wes tern blot analysis showed the presence of a protein with an apparent molecu lar mass of 66 kDa in the adrenal cortex but not in the medulla. Taken toge ther, these data demonstrate that the rat adrenal glomerulosa expresses fun ctional 5-HT7 receptors. Rat glomerulosa cells will thus provide a robust a nd sensitive bioassay for future studies on native 5-HT7 receptors.