Activation of 5-HT(7) receptor in rat glomerulosa cells is associated with an increase in adenylyl cyclase activity and calcium influx through T-type calcium channels

Endocrinology. 2002 May;143(5):1748-60. doi: 10.1210/endo.143.5.8817.


Serotonin (5-HT) stimulates aldosterone secretion from the rat adrenal gland through 5-HT(7) receptors. The aim of the present study was to investigate the transduction mechanisms associated with activation of 5-HT(7) receptors in rat glomerulosa cells. The stimulatory effect of 5-HT on aldosterone secretion and cAMP formation was significantly reduced by the 5-HT(7) receptor antagonist LY 215840. Pretreatment of cells with the adenylyl cyclase inhibitor SQ 22536 or the PKA inhibitor H-89 markedly attenuated the effect of 5-HT on aldosterone secretion. Conversely, type 2 and 4 phosphodiesterase inhibitors potentiated the 5-HT-induced stimulation of aldosterone secretion. Administration of 5-HT in the vicinity of cultured glomerulosa cells induced a slowly developing and robust increase in cytosolic calcium concentration ([Ca(2+)](i)). The effect of 5-HT on [Ca(2+)](i) was suppressed by mibefradil, a T-type calcium channel blocker. Patch-clamp studies confirmed that 5-HT activated a T-type calcium current. Mibefradil also induced a dose-dependent inhibition of 5-HT-induced aldosterone secretion. The sequence of events associated with activation of 5-HT(7) receptors was investigated. The PKA inhibitor H-89 markedly attenuated both the [Ca(2+)](i) response and the activation of T-type calcium current induced by 5-HT. In contrast, reduction of the calcium concentration in the incubation medium did not affect 5-HT- induced cAMP formation. Preincubation of glomerulosa cells with cholera toxin abolished the stimulatory effect of 5-HT on aldosterone secretion, but pertussis toxin had no effect. Taken together, these data demonstrate that, in rat glomerulosa cells, activation of native 5-HT(7) receptors stimulates cAMP formation through a G(salpha) protein, which in turn provokes calcium influx through T-type calcium channels. Both the adenylyl cyclase/PKA pathway and the calcium influx are involved in 5-HT-induced aldosterone secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / metabolism*
  • Aldosterone / metabolism
  • Animals
  • Calcium / metabolism*
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism
  • Calcium Channels, T-Type / metabolism*
  • Cell Separation
  • Cyclic AMP / analysis
  • Cyclic AMP / biosynthesis
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Cytosol / drug effects
  • Cytosol / metabolism
  • Enzyme Inhibitors / pharmacology
  • Female
  • GTP-Binding Proteins / antagonists & inhibitors
  • GTP-Binding Proteins / physiology
  • Male
  • Perfusion
  • Phosphodiesterase Inhibitors / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / metabolism*
  • Serotonin / pharmacology
  • Signal Transduction / physiology
  • Zona Glomerulosa / cytology
  • Zona Glomerulosa / enzymology
  • Zona Glomerulosa / metabolism*


  • Calcium Channels
  • Calcium Channels, T-Type
  • Enzyme Inhibitors
  • Phosphodiesterase Inhibitors
  • Receptors, Serotonin
  • serotonin 7 receptor
  • Serotonin
  • Aldosterone
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • GTP-Binding Proteins
  • Adenylyl Cyclases
  • Calcium