Caffeine modulates Ca2+ receptor activation in isolated rat osteoclasts and induces intracellular Ca2+ release
Shankar, V.S.; Pazianas, M.; Huang, C.L.; Simon, B.; Adebanjo, O.A.; Zaidi, M.
American Journal of Physiology 268(3 Pt 2): F447-F454
1995
ISSN/ISBN: 0002-9513 PMID: 7900844 Document Number: 453983
A ryanodine-sensitive pathway is involved in intracellular Ca-2+ release in response to activation of the osteoclast cell surface Ca-2+ receptor. We now report that the ryanodine-receptor modulator, caffeine itself released intracellularly stored Ca-2+ and, strongly inhibited Ca-2+ release triggered in response to Ca-2+-receptor activation by Ni-2+, a surrogate cation agonist. Caffeine yielded a bell-shaped concentration-response curve (0.005-2 mM) and displayed use-dependent inactivation. Furthermore, responses to caffeine were abolished on prior application of Ni-2+ (5 mM). Subthreshold (0.005 mM) caffeine concentrations abolished Ni-2+-induced elevations in the cytosolic Ca-2+ concentration ((Ca-2+)). However, in a Ca-2+-free, ethylene glycol-bis(beta-aminoethyl ether)N,N,N',N'-tetraacetic acid-containing solution (extracellular (Ca-2+) lt 10 nM), caffeine (0.5 mM) neither elevated (Ca-2+) nor inhibited the response to Ni-2+. Finally, when caffeine was applied to intercept the plateau phase of the cytosolic Ca-2+ signal triggered by extracellular Ca-2+ elevation (10 mM), a rapid but reversible inactivation followed. These studies strongly indicate the existence of a caffeine-sensitive mechanism for the release of intracellularly stored Ca-2+ in the osteoclast.