Comparative pharmacology of two D1-like dopamine receptors cloned from the silkworm Bombyx mori |
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| Authors: | Hiroto Ohta Kazuko Tsuchihara Kanako Mitsumasu Toshinobu Yaginuma Yoshihisa Ozoe Kiyoshi Asaoka |
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| Institution: | 1. Biocontrol and Insect Pathology Laboratory, Department of Plant Protection, School of Agriculture, Ferdowsi University of Mashhad, Mashhad, Iran;2. Department of Plant Protection, College of Agriculture Science, University of Guilan, Rasht, Iran;3. Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran;1. Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, 4 rue Gabrielle-Perret-Gentil, 1205 Geneva, Switzerland;2. Division of Cardiology, Foundation for Medical Researches, Department of Medical Specialties, University of Geneva, 64 avenue de la Roseraie, 1211 Geneva, Switzerland;3. Department of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino–IST Istituto Nazionale per la Ricerca sul Cancro, 6 viale Benedetto XV, 16132 Genoa, Italy;4. Cardiac, Thoracic and Vascular Department, University of Pisa, Azienda Universitaria-Ospedaliera Pisana, Via Paradisa, 2, 56124 Pisa, Italy;5. Serviço de Cardiologia 1, Hospital de Santa Maria (CHLN), Lisboa, Portugal;6. Vascular and Endovascular Surgery Unit, Department of Surgery, San Martino Hospital, 10 Largo Rosanna Benzi, 16132 Genoa, Italy;7. Department of Nuclear Medicine Unit, IRCCS San Martino-IST, University of Genoa, L.go R. Benzi 10, 16132 Genoa, Italy;8. Institute of Cardiology and Center of Excellence on Aging, G. d''Annunzio University – Chieti-Pescara, Italy;9. G. Monasterio Foundation, Pisa, Italy |
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| Abstract: | Dopamine (DA) is a physiologically important biogenic amine in insect peripheral and nervous tissues. We recently cloned two DA receptors (BmDopR1 and BmDopR2) from the silkworm Bombyx mori and identified them as D1-like receptors, which activate adenylate cyclase to increase intracellular cAMP levels. In this study, these two receptors were stably expressed in HEK-293 cells, and the dose-responsiveness to DA and their pharmacological properties were examined using cAMP assays. BmDopR1 showed a dose-dependent increase in cAMP levels at DA concentrations up to 10?7 M with EC50 of 3.30 nM, while BmDopR2 required 10?6 M DA for activation. In BmDopR1-expressing cells, DA at 10?6–10?4 M induced 30–50% lower cAMP production than 10?7 M DA. BmDopR2-expressing cells showed a standard sigmoidal dose–response, with maximum cAMP levels attained with 10?5–10?4 M DA and EC50 of 1.30 μM. Both receptors had similar agonist profiles, and the typical vertebrate D1-like receptor agonist SKF-38393 was ineffective. Experiments with antagonists revealed that BmDopR1 exhibits D1-like features. However, the pharmacology of BmDopR2 was distinct from D1-like receptors; the typical vertebrate D1-like receptor antagonist SCH-23390 was less potent than the nonselective antagonist flupenthixol and the D2-like receptor antagonist chlorpromazine. The rank order of activities of several antagonists for BmDopR1 and BmDopR2 was more similar to that of Drosophila melanogaster DA receptors than Apis mellifera DA receptors. These data suggest that DA receptors could be potential targets for specific insecticides or insectistatics. |
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