Serotonin 5-HT2C receptor stimulates cyclic GMP formation in choroid plexus

J Neurochem. 1995 Jan;64(1):199-205. doi: 10.1046/j.1471-4159.1995.64010199.x.


The serotonin 5-HT2C receptor (formerly designated the 5-HT1C receptor) of the choroid plexus triggers phosphoinositide turnover. In the present study, we demonstrate that receptor activation also triggers the formation of cyclic GMP (cGMP). Application of 1 microM 5-HT to porcine choroid plexus tissue slices resulted in stimulation of cGMP formation to a maximum of five-fold basal level, with an EC50 of 11 nM. This response was not inhibited by muscarinic or beta-adrenergic receptor antagonists. Serotonin receptor antagonists inhibited cGMP formation with apparent Ki values of 1.3 (mianserin), 200 (ketanserin), and 5,500 (spiperone) nM, respectively. Neither serotonin-stimulated cGMP formation nor PI turnover was inhibited by pertussis toxin pretreatment. Preliminary biochemical studies suggested that serotonin-stimulated cGMP formation was calcium, phospholipase A2, and lipoxygenase dependent, as incubation in low calcium buffers or inclusion of the phospholipase A2 or lipoxygenase inhibitors p-bromophenacylbromide or BW 755c resulted in significant reduction of cGMP formation. The present results suggest that in addition to triggering phosphoinositide turnover, choroid plexus serotonin 5-HT2C receptors trigger cGMP formation in a calcium-sensitive manner.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cattle
  • Choroid Plexus / drug effects
  • Choroid Plexus / metabolism*
  • Cyclic GMP / metabolism*
  • Ketanserin / pharmacology
  • Mianserin / pharmacology
  • Phosphatidylinositols / metabolism
  • Receptors, Serotonin / physiology*
  • Spiperone / pharmacology
  • Swine


  • Phosphatidylinositols
  • Receptors, Serotonin
  • Mianserin
  • Spiperone
  • Ketanserin
  • Cyclic GMP