INHIBITION OF CALCIUM HYDROXYAPATITE FORMATION BY POLYAMINES

The lithogenic potential of bile depends not only on supersaturation o f solutes but also on the presence of pro- and anti-nucleating factors . For example, glycine-conjugated dihydroxy bile salt dimers are poten t inhibitors of calcium hydroxyapatite precipitation that function by ''poisoning'' the nascent crystal. Although most inhibitors of apatite formation are anions, theoretically polycations should also be effect ive, and because significant concentrations of polyamines are present in bile, we have investigated the ability of these molecules to inhibi t apatite formation. In vitro, each polyamine (2-10 mmol/l) was able t o inhibit apatite formation, and the inhibiting power was correlated w ith ionic charge. Thus putrescine (2+) was the weakest inhibitor and s permine (4+) was the strongest. Mixtures of polyamines were less effec tive than were the individual polyamines, except at higher concentrati ons. Although polyamines were effective over short periods of time (27 0 min), over longer times (3 days) spermine was unable to prevent apat ite formation. Using infrared spectroscopy, we found no evidence for i nteraction between phosphate ions and spermine in solution. Taken toge ther, these results suggest that polyamines are modest inhibitors of a patite formation that likely function by retarding the dissolution of the intermediate amorphous calcium phosphate phase.