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

Abstract We report the cloning, molecular characterization, and pharmacological characterization of the canine 5-HT 2A and 5-HT 2B receptors. The canine and human 5-HT 2A receptors share 93% amino acid homology. The canine and human 5-HT 2B 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-HT 2A and 5-HT 2B receptors have high affinity for [ 3 H]5-HT ( K D  = 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 (Ca 2+ mobilization) of the canine 5-HT 2B receptor to several agonists was weaker compared to the human 5-HT 2B receptor. Using quantitative reverse transcriptase polymerase chain reaction, a high expression level of canine 5-HT 2A receptor mRNA was detected in the brain and lower levels in peripheral tissues, whereas the highest levels of canine 5-HT 2B receptor mRNA were observed in lungs and smooth muscles. A significant level of canine 5-HT 2B receptor mRNA was detected in brain tissue. The availability of the full sequence and pharmacology of the canine 5-HT 2A and canine 5-HT 2B receptors provides useful information for the interpretation of previous and future pharmacological studies of 5-HT 2A/2B ligands in dog.