Diverse actions of calcitonin gene-related peptide on intracellular free Ca2+ concentrations in UMR 106 osteoblastic cells.
Calcitonin gene-related peptide (CGRP) was examined for its effects on intracellular free Ca2+ concentration ([Ca2+]i) in UMR 106 osteoblast-like cells. Cells loaded with the Ca2+ dye FURA-2 dose-dependently responded to CGRP (1-100 nM) with transient two-fold increases in [Ca2+]i. An intracellular source for this Ca2+ transient was suggested by the failure of membrane depolarization with high extracellular K+ or acute depletion of extracellular Ca2+ ([Ca2+]e) with EGTA to attenuate this response. After cells were incubated for 45 min with 0.1 mM extracellular Ca2+ to deplete intracellular Ca2+ stores, CGRP produced a 25-30% decrease in [Ca2+]i rather than a transient increase. This calcium decrease was mimicked by membrane depolarization or by pinacidil, a specific activator of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels, and blocked by glybenclamide, a specific blocker of KATP channels. Our data suggest that CGRP has diverse Ca2+ regulatory effects in UMR 106 cells, mobilizing Ca2+ from intracellular stores via classical signaling while possibly promoting cellular Ca2+ efflux or inhibiting uptake through voltage-dependent Ca2+ channels via KATP-mediated hyperpolarization.
Kawase
T
T
Geriatric Research, Education, and Clinical Center, Veterans Affairs Medical Center, Miami, FL 33125, USA.
Howard
G A
GA
Roos
B A
BA
Burns
D M
DM
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001859:Bone Neoplasms / Q000473:pathology; D002116:Calcitonin / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D016257:Fura-2 / Q000737:chemistry; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012516:Osteosarcoma / Q000473:pathology; D020110:Pinacidil; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D013050:Spectrometry, Fluorescence; D014407:Tumor Cells, Cultured; D014665:Vasodilator Agents / Q000494:pharmacology
D006146:Guanidines; D015221:Potassium Channels; D014665:Vasodilator Agents; D005576:Colforsin; D004533:Egtazic Acid; D020110:Pinacidil; D000255:Adenosine Triphosphate; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide; D011188:Potassium; D005905:Glyburide; D002118:Calcium; D016257:Fura-2