Stimulation of type 1 and type 8 Ca2+/calmodulin-sensitive adenylyl cyclases by the G(s)-coupled 5-hydroxytryptamine subtype 5-HT(7A) receptor

Lauren P. Baker, Mark D. Nielsen, Soren Impey, Mark A. Metcalf, Steven W. Poser, Guy Chan, Karl Obrietan, Mark W. Hamblin, Daniel R. Storm

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) plays an important regulatory role in developing and adult nervous systems. With the exception of the 5-HT3 receptor, all of the cloned serotonin receptors belong to the G protein-coupled receptor superfamily. Subtypes 5-HT6 and 5- HT7 couple to stimulation of adenylyl cyclases through G(s) and display high affinities for antipsychotic and antidepressant drugs. In the brain, mRNA for 5-HT6 is found at high levels in the hippocampus, striatum, and nucleus accumbens. 5-HT7 mRNA is most abundant in the hippocampus, neocortex, and hypothalamus. To better understand how serotonin might control cAMP levels in the brain, we coexpressed 5-HT6 or 5-HT(7A) receptors with specific isoforms of adenylyl cyclase in HEK 293 cells. The 5-HT6 receptor functioned as a typical G(s)-coupled receptor in that it stimulated AC5, a G(s)-sensitive adenylyl cyclase, but not AC1 or AC8, calmodulin (CaM)-stimulated adenylyl cyclases that are not activated by G(s)-coupled receptors in vivo. Surprisingly, serotonin activation of 5-HT(7A) stimulated AC 1 and AC8 by increasing intracellular Ca2+. 5-HT also increased intracellular Ca2+ in primary neuron cultures. These data define a novel mechanism for the regulation of intracellular cAMP by serotonin.

Original languageEnglish (US)
Pages (from-to)17469-17476
Number of pages8
JournalJournal of Biological Chemistry
Volume273
Issue number28
DOIs
StatePublished - Jul 10 1998

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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