Molecular and pharmacological characterization of serotonin 5-HT2A and 5-HT2B receptor subtypes in dog

Eur J Pharmacol. 2005 Apr 25;513(3):181-92. doi: 10.1016/j.ejphar.2005.03.013. Epub 2005 Apr 20.

Abstract

We report the cloning, molecular characterization, and pharmacological characterization of the canine 5-HT2A and 5-HT2B receptors. The canine and human 5-HT2A receptors share 93% amino acid homology. The canine and human 5-HT2B receptors are also highly conserved (87% homology) with the exception of the carboxyl termini where the canine protein is 62 amino acids shorter. Both the canine 5-HT2A and 5-HT2B receptors have high affinity for [3H]5-HT (KD=4.50+/-0.89 nM and 3.10+/-0.82 nM, respectively) and, in general, the pharmacology of these two receptors matches closely the pharmacology of their human homologs for the 19 serotonergic ligands tested. However, the functional response (Ca2+ mobilization) of the canine 5-HT2B receptor to several agonists was weaker compared to the human 5-HT2B receptor. Using quantitative reverse transcriptase polymerase chain reaction, a high expression level of canine 5-HT2A receptor mRNA was detected in the brain and lower levels in peripheral tissues, whereas the highest levels of canine 5-HT2B receptor mRNA were observed in lungs and smooth muscles. A significant level of canine 5-HT2B receptor mRNA was detected in brain tissue. The availability of the full sequence and pharmacology of the canine 5-HT2A and canine 5-HT2B receptors provides useful information for the interpretation of previous and future pharmacological studies of 5-HT2A/2B ligands in dog.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Calcium / metabolism
  • Cell Line
  • Chlorocebus aethiops
  • Cloning, Molecular
  • Dogs
  • Humans
  • Molecular Sequence Data
  • Organ Specificity
  • RNA, Messenger / biosynthesis
  • Radioligand Assay
  • Receptor, Serotonin, 5-HT2A / biosynthesis
  • Receptor, Serotonin, 5-HT2A / drug effects*
  • Receptor, Serotonin, 5-HT2A / genetics*
  • Receptor, Serotonin, 5-HT2B / biosynthesis
  • Receptor, Serotonin, 5-HT2B / drug effects*
  • Receptor, Serotonin, 5-HT2B / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Species Specificity
  • Transfection

Substances

  • RNA, Messenger
  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT2B
  • Calcium