title: Platypus and opossum calcitonins exhibit strong activities, even though they belong to mammals.
abstract: In mammalian assay systems, calcitonin peptides of non-mammalian species exhibit stronger activity than those of mammals. Recently, comparative analyses of a wide-range of species revealed that platypus and opossum, which diverged early from other mammals, possess calcitonins that are more similar in amino acid sequence to those of non-mammals than mammals. We herein determined whether platypus and opossum calcitonins exhibit similar biological activities to those of non-mammalian calcitonins using an assay of actin ring formation in mouse osteoclasts. We also compared the dose-dependent effects of each calcitonin on cAMP production in osteoclasts. Consistent with the strong similarities in their primary amino acid sequences, platypus and opossum calcitonins disrupted actin rings with similar efficacies to that of salmon calcitonin. Human calcitonin exhibited the weakest inhibitory potency and required a 100-fold higher concentration (EC50=3×10-11M) than that of salmon calcitonin (EC50=2×10-13M). Platypus and opossum calcitonins also induced cAMP production in osteoclast cultures with the same efficacies as that of salmon calcitonin. Thus, platypus and opossum calcitonins exhibited strong biological activities, similar to those of the salmon. In addition, phylogenetic analysis revealed that platypus and opossum calcitonins clustered with the salmon-type group but not human- or porcine-type group. These results suggest that platypus and opossum calcitonins are classified into the salmon-type group, in terms of the biological activities and amino acid sequences.
authors.affiliation: Institute for Oral Science, Matsumoto Dental University, 1780 Hirooka-Gobara, Shiojiri, Nagano 399-0781, Japan. Electronic address: teru@po.mdu.ac.jp.
authors.forename: Teruhito
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Department of Oral Biochemistry, Matsumoto Dental University, 1780 Hirooka-Gobara, Shiojiri, Nagano 399-0781, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Udagawa
authors.affiliation: Institute for Oral Science, Matsumoto Dental University, 1780 Hirooka-Gobara, Shiojiri, Nagano 399-0781, Japan.
authors.forename: Gnanasagar Janardhanan
authors.initials: GJ
authors.lastname: Thirukonda
authors.affiliation: Department of Oral Biochemistry, Matsumoto Dental University, 1780 Hirooka-Gobara, Shiojiri, Nagano 399-0781, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Uehara
authors.affiliation: Institute for Oral Science, Matsumoto Dental University, 1780 Hirooka-Gobara, Shiojiri, Nagano 399-0781, Japan; Japan Osteoporosis Foundation, 11-2 Nihonbashi-kobunacho, Chuo-ku, Tokyo 103-0024, Japan.
authors.forename: Hirose
authors.initials: H
authors.lastname: Yamauchi
authors.affiliation: Noto Marine Laboratory, Institute of Nature and Environment Technology, Kanazawa University, 4-1 Ogi, Noto-cho, Ishikawa 927-0553, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Suzuki
authors.affiliation: Institute of Nature Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Institute for Oral Science, Matsumoto Dental University, 1780 Hirooka-Gobara, Shiojiri, Nagano 399-0781, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Institute for Oral Science, Matsumoto Dental University, 1780 Hirooka-Gobara, Shiojiri, Nagano 399-0781, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Takahashi
mesh_terms: D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D002116:Calcitonin / Q000494:pharmacology*; D002478:Cells, Cultured; D002942:Circular Dichroism; D000242:Cyclic AMP / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009893:Opossums / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments; D010802:Phylogeny; D010987:Platypus / Q000378:metabolism*; D012474:Salmon; D017386:Sequence Homology, Amino Acid
chemical_list: D000199:Actins; D050071:Bone Density Conservation Agents; D010446:Peptide Fragments; D002116:Calcitonin; D000242:Cyclic AMP
keywords: Actin ring; Calcitonin; Marsupial; Monotreme; Osteoclast; cAMP