Serotonin 5-HT2C receptor stimulates cyclic GMP formation in choroid plexus.
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.
Kaufman
M J
MJ
Department of Environmental Health Sciences, Johns Hopkins University, Baltimore.
Hartig
P R
PR
Hoffman
B J
BJ
D000818:Animals; D002417:Cattle; D002831:Choroid Plexus / Q000187:drug effects / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D007650:Ketanserin / Q000494:pharmacology; D008803:Mianserin / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D011985:Receptors, Serotonin / Q000502:physiology*; D013134:Spiperone / Q000494:pharmacology; D013552:Swine
D010716:Phosphatidylinositols; D011985:Receptors, Serotonin; D008803:Mianserin; D013134:Spiperone; D007650:Ketanserin; D006152:Cyclic GMP