Endocrinology, Vol 137, 984-990, Copyright © 1996 by Endocrine Society

ARTICLES

Calcitonin gene-related peptide rapidly inhibits calcium uptake in osteoblastic cell lines via activation of adenosine triphosphate- sensitive potassium channels

T Kawase, GA Howard, BA Roos and DM Burns
Geriatric Research, Education, and Clinical Center, Veterans Affairs Medical Center, Miami, Florida 33125, USA.

In certain neurons, alternative RNA processing generates calcitonin gene-related peptide (CGRP) from the same gene that encodes the hormone calcitonin. As CGRP-containing nerve fibers are prominent in skeleton, we evaluated the effects of CGRP on osteoblasts. Because the vasodilatory effect of neural CGRP in smooth muscle probably involves inhibition of unstimulated Ca2+ uptake, we examined the acute effects of CGRP on this parameter in rat osteoblastic cells. CGRP inhibits 45Ca2+ uptake in both UMR 106 osteosarcoma and RCOB-3 osteoblastic cells. This inhibition is rapid (0.5 min), occurs with an EC50 of 1 nM, and cannot be demonstrated in the presence of 0.1 mM diltiazem, a blocker of voltage-dependent Ca2+ channels. Depolarization of bone cells with high extracellular potassium (K+) also blocks the effect of CGRP on 45Ca2+ uptake, suggesting a central role for K+ channels in mediating this action. In agreement with this hypothesis, the effect of CGRP is blocked by 1 microM glybenclamide, a specific inhibitor of ATP- sensitive potassium (K(ATP)) channels, or by pretreatment of cells with 1 mM iodoacetic acid to deplete intracellular ATP. Blocking Ca2+- activated potassium channels with 1 mM tetraethylammonium does not prevent CGRP's effect. Pinacidil, a specific activator of K(ATP) channels, mimics CGRP's effect. Both CGRP and pinacidil also produce a small significant stimulation of cellular Ca2+ efflux in UMR 106 cells. These data suggest that inhibition of diltiazem-sensitive Ca2+ channels occurs secondary to the hyperpolarization engendered by CGRP activation of K(ATP) channels in osteoblastic cells, an effect similar to that of CGRP on smooth muscle cells.

This article has been cited by other articles:

				T. Kawase, K. Okuda, and D. M. Burns Immature osteoblastic MG63 cells possess two calcitonin gene-related peptide receptor subtypes that respond differently to [Cys(Acm)2,7] calcitonin gene-related peptide and CGRP8-37 Am J Physiol Cell Physiol, October 1, 2005; 289(4): C811 - C818. [Abstract] [Full Text] [PDF]

				D. M. Burns, L. Stehno-Bittel, and T. Kawase Calcitonin gene-related peptide elevates calcium and polarizes membrane potential in MG-63 cells by both cAMP-independent and -dependent mechanisms Am J Physiol Cell Physiol, August 1, 2004; 287(2): C457 - C467. [Abstract] [Full Text] [PDF]

				T. Kawase and D. M. Burns Calcitonin Gene-Related Peptide Stimulates Potassium Efflux through Adenosine Triphosphate-Sensitive Potassium Channels and Produces Membrane Hyperpolarization in Osteoblastic UMR106 Cells Endocrinology, August 1, 1998; 139(8): 3492 - 3502. [Abstract] [Full Text] [PDF]