RT Journal Article SR Electronic T1 Insoluble Solid Complexes of Norepinephrine and Adenosine Triphosphate JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 88 OP 94 VO 8 IS 1 A1 E. W. MAYNERT A1 B. H. MOON A1 V. S. PAI YR 1972 UL http://molpharm.aspetjournals.org/content/8/1/88.abstract AB Dilution with H2O of aqueous solutioins 0.5 M in norepinephrine HCl and 0.125 M in ATP (pH range, 3-7) yielded precipitates in 5-10% yield. In contrast, the products obtained by lyophilization of either the concentrated solutions or the filtrates from the precipitates readily dissolved in the original volume of H2O. The insoluble solid obtained at pH 7 had the proper elementary composition and infrared and 1H nuclear magnetic resonance spectra for a 4:1 norepinephrine·ATP complex. The precipitate produced at pH 3 was composed mostly of the 3:1 complex but appeared to contain a small amount of the 4:1 complex. In the preparation of these solids, ATP could be used as the 2Na+, Mg++, or 2(CH3)4N+ salt, but no precipitates were observed when norepinephrine bitartrate or the hydrochlorides of epinephrine or a variety of other phenethylamines were substituted for norepinephrine HCl. The maximum solubility of the complexes in H2O was estimated at 0.2 mM. This value was approximately doubled in 1.5% NaCl or KCl, and increased about 50 times in MgCl2 or CaCl2 of the same concentration. Dilution of aqueous solutions containing norepinephrine and ADP precipitated a 3:1 complex at pH 7, and a 2:1 complex at pH 3. AMP also formed an insoluble complex. The 4:1 norepinephrine·ATP complex was recovered unchanged upon neutralization of a solution in 0.1 N HCl. However, longer exposure to acidic conditions yielded the 3:1 norepinephrine·ADP complex. The 4:1 norepinephrine·ATP complex was more resistant to hydrolysis in 0.1 N HC1 than was ATP or a mixture of norepinephrine and ATP. Insoluble complexes of catecholamines and ATP could account for the calculated hypertonicity and the nondiffusibility of the amines in adrenal medullary granules.