Dual couplings of the cloned 5-HT1A receptor to both adenylyl cyclase and phospholipase C is mediated via the same Gi protein

Annick Fargin, Kiohei Yamamoto, Susanna Cotecchia, Paul K. Goldsmith, Allen M. Spiegel, Eduardo G. Lapetina, Marc G. Caron, Robert J. Lefkowitz

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


The coloned 5-HT1A receptor, stably expressed in HeLa cells, has been shown to mediate the effects of 5-hydroxytryptamine (5-HT) to inhibit cAMP formation and to stimulate the hydrolysis of phosphatidylinositol. Both responses were found to be pertussis toxin sensitive. We have examined these two responses in membranes derived from these cells and show that the 5-HT1A receptor can directly regulate the activity of adenylyl cyclase and phospholipase C in response to agonist. In order to examine whether the same or distinct guanine nucleotide-binding regulatory protein(s) (G protein) are involved in these two signal transduction pathways, we used anti-peptide antibodies recognizing the α-subunits of Gi1, Gi2, Gi3 as specific tools, since these pertussis toxin substrates are expressed in HeLa cells. These antibodies have previously been shown to prevent receptor-G protein coupling by binding to the regions of G proteins which are putatively involved in interaction with receptors. Our results indicate that the Gi proteins, but preferentially G3, mediate the effects of 5-HT both to inhibit adenylyl cyclase and to stimulate phospholipase C. These findings demonstrate that the same receptor interacting with the same C protein can regulate several distinct effector molecules.

Original languageEnglish (US)
Pages (from-to)547-557
Number of pages11
JournalCellular Signalling
Issue number6
StatePublished - 1991
Externally publishedYes


  • 5-HT receptor
  • G proteins
  • adenylyl cyclase
  • phospholipase C
  • signal transduction

ASJC Scopus subject areas

  • Cell Biology


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