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Serotonin 5‐HT 2C Receptor Stimulates Cyclic GMP Formation in Choroid Plexus
Author(s) -
Kaufman Marc J.,
Hartig Paul R.,
Hoffman Beth J.
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.64010199.x
Subject(s) - medicine , endocrinology , serotonin , pertussis toxin , ketanserin , choroid plexus , receptor , stimulation , serotonergic , chemistry , biology , 5 ht receptor , g protein , central nervous system
The serotonin 5‐HT 2C receptor (formerly designated the 5‐HT 1C 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 µ M 5‐HT to porcine choroid plexus tissue slices resulted in stimulation of cGMP formation to a maximum of five‐fold basal level, with an EC 50 of 11 n M . This response was not inhibited by muscarinic or β‐adrenergic receptor antagonists. Serotonin receptor antagonists inhibited cGMP formation with apparent K i values of 1.3 (mianserin), 200 (ketanserin), and 5,500 (spiperone) n M , 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 A 2 , and lipoxygenase dependent, as incubation in low calcium buffers or inclusion of the phospholipase A 2 or lipoxygenase inhibitors p ‐bromophenacyl bromide 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‐HT 2C receptors trigger cGMP formation in a calcium‐sensitive manner.