Functional expression of human 5-HT1A receptors and differential coupling to second messengers in CHO cells

Naunyn Schmiedebergs Arch Pharmacol. 1992 Aug;346(2):127-37. doi: 10.1007/BF00165293.


The signal transduction linkages of the cloned human 5-HT1A receptor as expressed stably in CHO cells were studied. A transfected clonal cell line which expresses 900 +/- 36 fmol 5-HT1A receptor/mg protein (designated CHO-5-HT1A/WT-27) responded to 5-HT and/or 8-OH-DPAT by coupling to several second messenger pathways. The 5-HT1A receptor inhibited, but did not stimulate, membrane adenylyl cyclase activity and whole cell cAMP accumulation in a dose-dependent manner (for 5-HT, IC50 = 146 +/- 27 and 55 +/- 12 nM, respectively). Activation of the receptor was associated with other signal transduction linkages: (i) a 40-50% increase in hydrolysis of inositol phosphates (for 5-HT, EC50 = 1.33 +/- 0.15 microM for 5-HT), (ii) a transient elevation of cytosolic Ca2+ levels (apparent at 1-100 microM 5-HT) which was not affected by chelation of extracellular Ca2+ by EGTA, and (iii) an augmentation of [3H]-arachidonic acid release pharmacologically with the calcium ionophore A23187 or by activation of endogenous thrombin or P2 purinergic receptors (for 5-HT, EC50 = 1.22 +/- 0.17 microM). This pathway may be an amplification mechanism for signaling in anatomic regions with high concentrations of several neuro-transmitters, hormones or autacoids, such as at neuronal junctions or near areas of platelet aggregation. All linkages were sensitive to pertussis toxin pre-treatment (IC50 approximately 0.5-0.6 ng/ml x 4.5 h for all pathways), suggesting the involvement of Gi protein(s) in these signal transduction pathways. Coupling to varied signal transduction pathways in a single cell system may be a common feature of receptors which classically inhibit adenylyl cyclase such as the 5-HT1A receptor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenylate Cyclase Toxin
  • Adenylyl Cyclase Inhibitors
  • Adenylyl Cyclases / metabolism
  • Amino Acid Sequence
  • Animals
  • Arachidonic Acid / metabolism
  • CHO Cells / physiology*
  • Calcium / metabolism
  • Cells, Cultured
  • Cricetinae
  • Humans
  • Inositol Phosphates / metabolism
  • Intracellular Fluid / metabolism
  • Kinetics
  • Molecular Sequence Data
  • Pertussis Toxin
  • Receptors, Serotonin / physiology*
  • Second Messenger Systems / physiology*
  • Sensitivity and Specificity
  • Stimulation, Chemical
  • Virulence Factors, Bordetella / pharmacology


  • Adenylate Cyclase Toxin
  • Adenylyl Cyclase Inhibitors
  • Inositol Phosphates
  • Receptors, Serotonin
  • Virulence Factors, Bordetella
  • Arachidonic Acid
  • Pertussis Toxin
  • Adenylyl Cyclases
  • Calcium