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Pharmacological Characterization of Human, Monkey and Rat MT1 and MT2 Receptors
Author(s) -
LoprestiMorrow Lori Lynn,
Beveridge Ramsay,
Carpino Philip A,
Cameron Kimberly O,
Chorabik Elizabeth,
Lingala Pavan,
Loria Paula M,
Petras Carol,
Rogers Lucy,
Chin Janice E
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.626.8
Pharmacological characterization of receptors at the species level is important in drug discovery to evaluate efficacy and safety. When using an animal model to evaluate efficacy and safety the pharmacological profile of the compounds in the animal species must align with the human pharmacological profile in order to interpret the data correctly. Differences in pharmacological profiles between ovine and human MT1 receptors as well as rat and human MT1 and MT2 receptors have been reported. Therefore, in this study we evaluated a panel of known MT1 and MT2 ligands for binding affinity and function against human, monkey and rat MT1 and MT2 receptors. Human, monkey and rat MT1 and MT2 receptor recombinately expressing cell lines were developed using the Invitrogen CHO‐FLP‐IN TREX system. Several melatonin ligands were characterized in binding assays using human, monkey and rat MT1 and MT2 expressing cell membranes and 2‐[125I]‐iodomelatonin. Functionality of the ligands were evaluated in [35S]‐GTP‐[gamma]‐binding assays in agonist and antagonist mode. Differences in binding affinity and functionality between human and rat receptors were observed but no differences between human and monkey were observed. Therefore, species differences in the pharmacology will have an impact on interpretation of the efficacy and safety data.