YM175, a new bisphosphonate, increases serum 1,25-dihydroxyvitamin D in rats via stimulating renal 1-hydroxylase activity

Effect of YM175, a new bisphosphonate, on vitamin D metabolism was studied in rats. When animals were treated with the compound, serum 1,25-dihydroxyvitamin D increased in a dose dependent manner. The effect was also detected in thyroparathyroidectomized animals. The effect appears to be due to the stimulation of renal production of the hormone, since renal 1-hydroxylase was also elevated in these animals. However, when kidneys were incubated with YM175 and then renal 1-hydroxylase activity was examined, the enzyme activity was not different from that of non-treated control kidney. We conclude therefore that YM175 indirectly stimulates renal 25-hydroxyvitamin D-1-hydroxylase by increasing circulating parathyroid hormone via an unknown mechanism independent of parathyroid hormone. This is the first direct demonstration of increase in the renal production of 1,25-dihydroxyvitamin D resulting from bisphosphonate treatment.     

Presence of histamine H2-receptors on human gastric carcinoma cell line MKN-45 and their increase by retinoic acid treatment.

Histamine dose-dependently stimulated cyclic AMP production in human gastric carcinoma cell line MKN-45, and this effect was inhibited by cimetidine but not by pyrilamine. Moreover, not only histamine but also cimetidine displaced the specific binding of [3H]tiotidine to these cells, whereas pyrilamine had no effect. On the other hand, pretreatment of MKN-45 cells with retinoic acid (RA) significantly enhanced histamine-induced increase of cyclic AMP production, although the cyclic AMP response to either forskolin or NaF was not affected. Finally, RA treatment increased the number of histamine receptor without altering its affinity. Thus, it appears that histamine H2-receptors are present on MKN-45 cells, and that RA treatment enhances the action of histamine on these cells by increasing the number of H2-receptors.     

Negative ion fast atom bombardment-tandem mass spectrometry for structural analysis of isoprenoid diphosphates

Applicability of negative ion fast atom bombardment (FAB)-tandem mass spectrometry (MS/MS) was examined in trace mixture analyses and structural assignments of some isoprenoid diphosphates. Negative ion FAB-MS spectra using a glycerol matrix of these isoprenoid diphosphates showed predominantly molecular ions (M-H)- together with fragment ions at m/z 177 (H3P2O7)-, 176 (H2P2O7)-, 159 (HP2O6)-, and 79 (PO3)- which were characteristic of the diphosphate ester moiety. The molecular ions did not overlap with peaks arising from any impurities even when crude sample such as butanol extracts from enzymatic reaction mixtures were directly analyzed without any purification. Moreover, collisionally activated dissociation spectra of the molecular ion showed many structurally significant fragment ions which enabled us to elucidate the structures of such irregular alkyl chain moieties as those having a homoisoprenoid skeleton or substituted structures. These studies indicate that negative ion FAB-MS/MS is a simple and useful technique for trace mixture analysis and structure elucidation of isoprenoid diphosphates.     

A respiration-dependent primary sodium extrusion system functioning at alkaline pH in the marine bacterium Vibrioalginolyticus

The membrane potential generated at pH 8.5 by K⁺-depleted and Na⁺-loaded $\text{Vibrio}\text{alginolyticus}$ is not collapsed by proton conductors which, instead, induce the accumulation of protons in equilibrium with the membrane potential. The generation of such a membrane potential and the accumulation of protons are specific to Na⁺-loaded cells at alkaline pH and are dependent on respiration. Extrusion of Na⁺ at pH 8.5 occurs in the presence of proton conductors unless respiration is inhibited while it is abolished by proton conductors at acidic pH. The uptake of α-aminoisobutyric acid, which is driven by the Na⁺-electrochemical gradient, is observed even in the presence of proton conductors at pH 8.5 but not at acidic pH. We conclude that a respiration-dependent primary electrogenic Na⁺ extrusion system is functioning at alkaline pH to generate the proton conductor-insensitive membrane potential and Na⁺ chemical gradient.     

Cartilage-derived factor (CDF) : II. Somatomedin-like action on cultured chondrocytes

Previously, we showed that fetal bovine cartilage contains a polypeptide that stimulates the incorporation of [³⁵S]sulfate into proteoglycans synthesized by rat and rabbit costal chondrocytes in culture. In this paper, we report that the cartilage-derived factor (CDF) increases not only [³⁵S]sulfate incorporation but also [³H]thymidine incorporation into rabbit chondrocytes in monolayer culture. The dose-response curve of CDF stimulation of DNA synthesis was similar in profile to that of CDF stimulation of proteoglycan synthesis. In addition, CDF markedly enhanced [³H]uridine incorporation into rabbit chondrocytes and significantly enhanced [³H]serine incorporation into total protein. These findings indicate that fetal bovine cartilage contains a factor that shows somatomedin-like activity in monolayer cultures of rabbit chondrocytes.     

A synthesis of 3′,4-́dideoxykanamycin B

3′,4′-Dideoxykanamycin B, the kanamycin B derivative that is active against resistant bacteria, was prepared from kanamycin B viaN-tosylation, 3′,4′-O-sulphonylation, 3′,4′-unsaturation, and hydrogenation. The unsaturated intermediate was obtained from the 3′,4′-di-O-sulphonyl derivatives by the action of sodium iodide in N,N-dimethylformamide; if zinc dust was added in this reaction, aziridine derivatives were formed, Removal of the tosyl group was successfully performed by using sodium in ammonia-ethylamine.