Trichorzin HA V, a member of the peptaibol family, stimulates intracellular cAMP formation in cells expressing the calcitonin receptor.
By a cell-based screening of an in-house natural product library, trichorzin HA V, belonging to a peptaibol family, was isolated from a strain of fungus Trichoderma as a calcitonin (CT) agonist. Like CT, trichorzin HA V elevated cAMP levels in T47D cells which endogenously express the human CT receptor. It also stimulated cAMP formation in cells expressing recombinant human CT receptor, but not in those that do not express the receptor, suggesting that it selectively interacts with the CT receptor. In contrast to trichorzin HA V, alamethicin, another well-characterized peptaibol, showed no cAMP-elevating activity at all. These results suggest that, although there was little amino acid sequence similarity between trichorzin HA V and CT, the biological activity of trichorzin HA V can mimic that of CT, acting via the CT receptor.
Katayama
T
T
Suntory Biomedical Research Limited, Mishima-gun, Osaka, Japan.
Miyagawa
K
K
Kodama
T
T
Oikawa
S
S
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007424:Intracellular Fluid / Q000378:metabolism*; D007476:Ionophores / Q000737:chemistry / Q000494:pharmacology; D054848:Peptaibols; D010455:Peptides; D018003:Receptors, Calcitonin / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D000900:Anti-Bacterial Agents; D036341:Intercellular Signaling Peptides and Proteins; D007476:Ionophores; D054848:Peptaibols; D010455:Peptides; D018003:Receptors, Calcitonin; C116937:peptaibolin; C113452:trichorzin PA V; D000242:Cyclic AMP