5-Hydroxytryptamine2A receptors expressed in rat renal mesangial cells inhibit cyclic AMP accumulation.
Journal Article (Journal Article)
Second messenger coupling of the 5-hydroxytryptamine (5-HT)2A receptor endogenous to cultured rat glomerular mesangial cells was studied. 5-HT induced an increase in total inositol phosphate levels (EC50 = 265 +/- 55 nM, maximum stimulation = 150 +/- 23%). That effect was sensitive to antagonists of the 5-HT2A receptor and was insensitive to pertussis toxin at doses that eliminated detectable pertussis toxin substrate, as determined by membrane ADP-ribosylation. Surprisingly, 5-HT also induced an inhibition of forskolin-stimulated cAMP accumulation (55 +/- 6%, IC50 = 5 +/- 3 nM). This effect was competitively antagonized by the 5-HT2A receptor antagonists ketanserin, ritanserin, and spiperone and could be produced by the 5-HT2 receptor agonists alpha-methyl-5-HT (66 +/- 13%, IC50 = 23 +/- 14 nM) and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (65 +/- 4%, IC50 = 14 +/- 7 nM). The inhibition of cAMP accumulation occurred in the presence of a number of agents that either stimulate or inhibit protein kinase C activity, arachidonic acid metabolism, or Ca2+ mobilization. In isolated membranes, 5-HT induced a 36 +/- 5% inhibition of adenylyl cyclase activity (IC50 = 8 +/- 4 nM). Inhibition of cAMP accumulation in intact cells and of adenylyl cyclase activity in washed membranes was (> 50%) sensitive to pertussis toxin, implicating Gi alpha or Go alpha subunits in the inhibitory signal. These data suggest that the 5-HT2A receptor can be permissive in its coupling to G proteins and second messengers.
Full Text
Duke Authors
Cited Authors
- Garnovskaya, MN; Nebigil, CG; Arthur, JM; Spurney, RF; Raymond, JR
Published Date
- August 1995
Published In
Volume / Issue
- 48 / 2
Start / End Page
- 230 - 237
PubMed ID
- 7651356
International Standard Serial Number (ISSN)
- 0026-895X
Language
- eng
Conference Location
- United States