Inhibition of parathyroid hormone-induced fetal rat bone resorption in vitro by nerve growth factor.
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Biomedical subjects
Publications and source records attributed to A J Kahn.
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Human circulating monocytes in tissue culture are capable of resorbing devitalized adult and fetal bone. An important component of this process is the adhesion of the cells to the mineralized substrate and the localized removal of matrix from beneath the attached cells. The process appears to involve both release of lysosomal enzymes onto the substrate and intracellular accumulation (transport) of resorbed matrix.
Chronic administration of high doses of anticonvulsant drugs frequently produces classic osteomalacia with bone histologic changes characteristic of increased parathyroid hormone (PTH) effect in man. However, several reports have documented defects in calcified tissue metabolism suggestive of an end-organ resistance to PTH after chronic anticonvulsant drug therapy. To examine the direct action of anticonvulsant drugs on bone resorption, we investigated the effects of diphenylhydantoin (phenytoin) (DPH) (100-200 mug/ml) and phenobarbital (10-400 mug/ml) on basal and hormonally mediated resorption 5-day cultures of fetal rat forelimb rudiments. In this system both drugs significantly inhibited basal and PTH-stimulated (45)Ca and [(3)H]hydroxyproline release, as well as 1,25-dihydroxyvitamin D(3)-stimulated (45)Ca release. The effects of DPH and phenobarbital were additive, with DPH exhibiting a several-fold more potent inhibitory effect than phenobarbital. Whereas DPH exhibited a striking synergism with the inhibitory effects of human calcitonin (HCT) on PTH-induced resorption, the effect of phenobarbital was merely additive to that of HCT. PTH and PTH plus HCT-induced increases in bone cyclic AMP (cAMP) content were significantly inhibited by DPH but not by phenobarbital. However, in contrast to effects on (45)Ca release, DPH inhibition of cAMP generation was not accentuated in the presence of HCT. It is concluded that: (a) both DPH and phenobarbital can directly inhibit basal and hormonally stimulated bone resorption, with DPH being much more potent in this regard; (b) DPH appears to inhibit bone resorption via a cAMP-independent mechanism and has an additional suppressive effect on PTH-induced cAMP generation; and (c) the synergistic interaction of DPH and HCT in inhibiting (45)Ca release occurs at a site independent of cAMP generation.
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Mice with a slower development of aversion to 3% ethanol solutions were slower to develop aggressive combat skills. Plasma testosterone levels did not decrease in another similarly treated group.
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C3H and CF1 mice that showed a delay in developing an aversive response to a 3% alcohol solution also had a delay in development of the parameter, total fluid intake per gram of body weight, which was not the result of alcohol consumption per se.
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Serotonin concentration in whole brain tissue of CF1 mice behaviorally attracted to a 3% alcohol solution was significantly depressed 48 hours after access to the solution was denied. Norepinephrine concentration was not affected.
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Water or a 3% alcohol solution was offered for 4 weeks to groups of male C3H mice initially aged 3, 13, 20 and 60 weeks, and to male CF1 mice from age 10 weeks until they died. Differences in the consumption depended on age and the rate at which response patterns to the solution develop.
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