title: A cloned porcine renal calcitonin receptor couples to adenylyl cyclase and phospholipase C.
abstract: The signal transduction pathways of the recently cloned porcine kidney calcitonin (CT) receptor were evaluated. This receptor, when stably transfected into MC-3T3 cells, avidly bound salmon CT (SCT) [dissociation constant (Kd) = 4 nM]. Incubation with SCT resulted in a dose-dependent accumulation of adenosine 3',5'-cyclic monophosphate (cAMP) [50% effective concentration (EC50) = 0.02 nM] in transfected cells (referred to as PC-1 cells). Binding kinetics and cAMP dose response relationships were similar to those of the native receptor in LLC-PK1 cells. PC-1 cells also responded to calcitonin gene-related peptide (CGRP), but the EC50 value for cAMP accumulation was more than three orders of magnitude higher than for SCT. Exposure of PC-1 cells to SCT (5 nM to 1 microM) produced a dose-dependent rise in cytosolic free Ca2+ concentration ([Ca2+]i), whereas CGRP did not. The initial rise in [Ca2+]i was not dependent on extracellular Ca2+, suggesting that SCT induced release of Ca2+ from intracellular stores. SCT also increased inositol trisphosphate production in PC-1 cells. In conclusion, the cloned, transfected porcine CT receptor functionally couples to and activates both adenylyl cyclase and phospholipase C. This dual coupling is also a characteristic of the parathyroid hormone receptor, which has significant homology in amino acid sequence with the CT receptor.
authors.affiliation: Arthritis Unit, Massachusetts General Hospital, Boston 02114.
authors.forename: T
authors.initials: T
authors.lastname: Force
authors.forename: J V
authors.initials: JV
authors.lastname: Bonventre
authors.forename: M R
authors.initials: MR
authors.lastname: Flannery
authors.forename: A H
authors.initials: AH
authors.lastname: Gorn
authors.forename: M
authors.initials: M
authors.lastname: Yamin
authors.forename: S R
authors.initials: SR
authors.lastname: Goldring
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002116:Calcitonin / Q000032:analysis / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002460:Cell Line; D003001:Cloning, Molecular; D003470:Culture Media; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D009994:Osmolar Concentration; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012474:Salmon / Q000378:metabolism; D015398:Signal Transduction; D013552:Swine; D010738:Type C Phospholipases / Q000378:metabolism*
chemical_list: D003470:Culture Media; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; D002116:Calcitonin; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases; D002118:Calcium