Inhibition of calcium hydroxyapatite formation by polyamines.
The lithogenic potential of bile depends not only on supersaturation of solutes but also on the presence of pro- and anti-nucleating factors. For example, glycine-conjugated dihydroxy bile salt dimers are potent 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 effective, and because significant concentrations of polyamines are present in bile, we have investigated the ability of these molecules to inhibit apatite formation. In vitro, each polyamine (2-10 mmol/l) was able to inhibit apatite formation, and the inhibiting power was correlated with ionic charge. Thus putrescine (2+) was the weakest inhibitor and spermine (4+) was the strongest. Mixtures of polyamines were less effective than were the individual polyamines, except at higher concentrations. Although polyamines were effective over short periods of time (270 min), over longer times (3 days) spermine was unable to prevent apatite formation. Using infrared spectroscopy, we found no evidence for interaction between phosphate ions and spermine in solution. Taken together, these results suggest that polyamines are modest inhibitors of apatite formation that likely function by retarding the dissolution of the intermediate amorphous calcium phosphate phase.
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77550-0764.
R C
RC
Crowther
C M
CM
Pritchard
S M
SM
Qiu
R D
RD
Soloway
D001646:Bile / Q000737:chemistry*; D015317:Biogenic Polyamines / Q000494:pharmacology*; D002130:Calcium Phosphates; D002769:Cholelithiasis / Q000737:chemistry; D017886:Durapatite; D006801:Humans; D006882:Hydroxyapatites / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D013055:Spectrophotometry, Infrared; D013997:Time Factors
D015317:Biogenic Polyamines; D002130:Calcium Phosphates; D006882:Hydroxyapatites; C519480:amorphous calcium phosphate; D017886:Durapatite