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5-HT1C receptor-mediated stimulation of inositol phosphate production in pig choroid plexus

A pharmacological characterization

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Summary

1) 5-HT (5-hydroxytryptamine, serotonin) induces inositol phosphate production in a pig choroid plexus preparation. This effect has been pharmacologically characterized and the data compared to those obtained from radioligand binding studies performed with [3H]mesulergine to 5-HT1C sites in pig choroid plexus membranes. 2) The rank order of potency of agonists stimulating inositol phosphate production was: α-methyl-5-HT > 1-methyl-5-HT > DOI > bufotenine = SKF 83566 = 5-HT > 5-MeO-DMT > 5-MeOT = RU 24969> SCH 23390> 5-CT. 8-OH-DPAT was virtually devoid of activity at 100 μmol/l. 3) The increase in inositol phosphate production induced by 5-HT and other agonists was surmountably antagonised by mesulergine, ketanserin and spiperone with pKB values of 8.7, 6.7 and 5.3, respectively. 4) The rank order of potency of antagonists was: metergoline > mesulergine > LY 53857 > ritanserin > methiothepin > mianserin > cyproheptadine > pirenperone > cinanserin > ketanserin > spiperone. The following antagonists were virtually devoid of activity at 100 μmol/l; pindolol, 21-009 and yohimbine. 5) The results obtained both with agonists and antagonists strongly support the view that 5-HT1C receptors mediate agonist induced production of inositol phosphates in pig choroid plexus. This is illustrated by the close similarity between 5-HT1C binding and stimulation of inositol phospholipid turnover in this preparation. 6) The present data also show that compounds believed to be selective for dopamine D1 receptors (SKF 83566, SCH 23390) or 5-HT2 receptors (DOI, α-methyl-5-HT, LY 53857, ritanserin, cyproheptadine) also interact with 5-HT1C receptors. 7) A case can be made for the 5-HT1C receptor, with its similarities to the 5-HT2 receptor in terms of pharmacology and second messenger coupling, being a 5-HT2 receptor subtype.

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Authors and Affiliations

  1. Preclinical Research, 386/525, Sandoz Ltd, CH-4002, Basel, Switzerland

    Daniel Hoyer, Christian Waeber, Philippe Schoeffter, Jose Maria Palacios & Anant Dravid

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  1. Daniel Hoyer
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  2. Christian Waeber
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  3. Philippe Schoeffter
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  4. Jose Maria Palacios
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  5. Anant Dravid
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Additional information

These data have been presented in part at the Spring Meeting of the German Pharmacological Society, March 1987 (Hoyer et al. 1987)

Send offprint requests to D. Hoyer at the above address

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Hoyer, D., Waeber, C., Schoeffter, P. et al. 5-HT1C receptor-mediated stimulation of inositol phosphate production in pig choroid plexus. Naunyn-Schmiedeberg's Arch Pharmacol 339, 252–258 (1989). https://doi.org/10.1007/BF00173573

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  • DOI: https://doi.org/10.1007/BF00173573

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