Effects of Divalent Cations and of a Calcimimetic on Adrenocorticotropic Hormone Release in Pituitary Tumor Cells
| Autor: | Martial Ruat, Christine Lair, Danielle Gully, Bruno Chatel, Jean-Pierre Maffrand, Robert H. Dodd, Sandrine Ferry |
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| Rok vydání: | 1997 |
| Předmět: |
Agonist
endocrine system medicine.medical_specialty Transcription Genetic Cations Divalent medicine.drug_class Calcimimetic Biophysics chemistry.chemical_element Receptors Cell Surface CHO Cells Adrenocorticotropic hormone Biology Calcium Biochemistry Adrenocorticotropic Hormone GTP-Binding Proteins Cricetinae Internal medicine Phenethylamines Tumor Cells Cultured medicine Extracellular Animals Magnesium Pituitary Neoplasms RNA Messenger Receptor Molecular Biology Aniline Compounds Propylamines Chinese hamster ovary cell Cell Biology Neoplasm Proteins Rats Endocrinology chemistry Barium Calcium-sensing receptor Receptors Calcium-Sensing |
| Zdroj: | Biochemical and Biophysical Research Communications. 238:866-873 |
| ISSN: | 0006-291X |
| Popis: | The calcium sensing receptor (CaSR), a member of the G-protein coupled receptor family, is expressed on a variety of cell types and responds to extracellular calcium. We have characterized pharmacological properties of (+/-)NPS 568, a calcimimetic, toward cloned rat brain extracellular Ca2+-sensing receptor (CaSR) expressed in Chinese hamster ovary (CHO) cells and constitutive mouse CaSR in AtT-20 cells. In the presence of 1.3 mM Ca2+, the calcimimetic displayed a potency in the micromolar range in augmenting the inositol phosphates (IP) response in both cell lines and behaved as a full agonist. (+/-)NPS 568 stimulated formation of arachidonic acid release in CHO(CaSR) with a similar potency. The IP dose response curves of (+/-)NPS 568 were shifted to the left in the presence of increasing Ca2+, indicating that the potency of the drug is dependent on extracellular Ca2+ in both cells. In AtT-20 cells, Ca2+ and Ba2+, two CaSR agonists, induced a potent stimulation of adrenocorticotropic hormone (ACTH) secretion. In the presence of 1.8 mM Ca2+, (+/-)NPS 568 led to a dose dependent secretion of ACTH with an EC50 of 0.3 microM and a maximal effect comparable to Ca2+. The similar potency of the calcimimetic on IP and ACTH responses and the sensitivity of these responses to extracellular Ca2+ indicate that the Ca2+-sensing receptor expressed in AtT-20 cells is implicated in ACTH release. These data further characterize the pharmacology of the Ca2+-sensing receptor and argue for a role for extracellular Ca2+ and CaSRs in controlling ACTH secretion, a hormone implicated in several types of stress. |
| Databáze: | OpenAIRE |
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