Lanthanum, inhibition binding

However, the effects of Ca are not seen with all stimuli the production of Of in response to phorbol myristate acetate was unaffected in medium lacking Ca, Lanthanum, which can act as a competitive inhibitor of Ca, reduced the effect of Ca in suspensions of PMNs stimulated with FMLP , That Ca acted by entering the cell was suggested because calcium ions did not affect the binding of FMLP. However, verapamil which blocks the channel for Ca in cell membranes, produced dose-dependent inhibition of the formation of Of and of the influx of Ca. This inhibition could be overcome by increasing the concentration of Ca in the medium . The reasons for the requirement of Ca for activation by some stimuli but not by others might be related to the site at which the stimulus in question acts. PMA, for example, might act at a site beyond the point at which Ca is required. 

Calcium binding was assayed by ultrafiltration and was found to exhibit a />H optimum at about 7.4. One class of binding sites is present which bind one mole of calcium per mole of protein with a dissociation constant equal to 2.5 X 10 5M. Calcium binding was competitively inhibited by other divalent cations the binding affinity being Ca++, Mn++, Sr++, Ba++, Mg++ (160). Lanthanum salts irreversibly precipitate brain CBP-II. Those cations which are the most effective inhibitors of calcium binding to this protein are also the most active for in vitro calcium-dependent release of neurotransmitters. 

Endocrine system. Lanthanum binds to the cell surface of parathyroid cells (without entering the cells), but this gives rise to increased Ca permeability resulting in a rise in intracellular Ca (Gylfe, Larsson et al. 1986). Parathyroid hormone (PTH) release from the gland is normally inhibited by Ca but is inhibited by lanthanum to an even greater extent. Incubation of parathyroid cells with pertussis toxin, a G-protein inactivator that blocks inhibition by Ca, does not block the inhibition of PTH release by lanthanum. There may be two cell surface sites that recognize lanthanmn and Ca independently (Fitzpatrick 1990).. 

---