Liangchai Limlomwongse

Bone calcium turnover, formation, and resorption in bromocriptine- and prolactin-treated lactating rats

To evaluate the effect of endogenous prolactin (PRL) on bone metabolism, we studied bone calcium turnover by the 45Ca kinetic method and bone formation and resorption by bone histomorphometry and biochemical markers in 13-wk-old lactating Wistar rats. For 1 wk, the animals received daily administration of 0.9% NaCl (control) intraperitoneally, 6 mg of bromocriptine/kg of body wt intraperitoneally, or 6 mg of bromocriptine/kg of body wt plus 2.5 mg of ovine PRL/kg of body wt subcutaneously. Bromocriptine, a dopaminergic inhibitor of endogenous PRL secretion, significantly decreased calcium ion deposit rate and calcium resorption rate in femur, tibia, vertebrae 5 and 6, and sternum by 20–42%. By contrast, calcium resorption rate of the vertebrae and the sternum of the PRL-treated group was higher than that of controls, whereas the tibia and sternum exhibited a greater net loss of calcium. The suppression of bone calcium turnover in the bromocriptine-treated group was further supported by a significant decrease in the urinary deoxypyridinoline, a biochemical index of bone resorption, and the histomorphometric data, which showed changes indicative of suppressed bone resorption and formation. The histomorphometric data from the PRL-treated group were not different from those of the control group with the exception of an increase in the longitudinal growth rate. The results suggested a role of endogenous PRL in the stimulation of bone turnover during lactation.

Acute effect of prolactin on the intestinal calcium absorption in normal, pregnant and lactating rats

Acute effect of prolactin on intestinal calcium absorption was studied in Wistar rats. Prolactin when given subcutaneously 24 h, or intraperitoneally 1 h, before intragastric administration of 45Ca-containing CaCl2 solution markedly increased the plasma 45Ca content. Of interest was the enhancing effect of prolactin on calcium transport seen in 1 h which suggested that prolactin could act directly on the intestine. Physiological significance of prolactin was evaluated in pregnant and lactating rats. Pretreatment with bromocriptine, an inhibitor of prolactin release, had no effect in rats on day 20 of pregnancy but significantly reduced calcium absorption in lactating rats. This reduced calcium absorption was only partially restored by prolactin treatment. The present investigation thus showed that prolactin, besides stimulating 1,25(OH2)D3 production, may also enhance calcium absorption directly. This effect was absent in pregnant rats but was of physiological significance in lactating rats.

Acute effect and mechanism of action of prolactin on the in situ passive calcium absorption in rat

Acute effect of prolactin (PRL) given intraperitoneally 1 h before on calcium fluxes was studied in 6 in situ intestinal segments from weaned, sexually mature and aged rats. In mature rats, PRL increased net passive calcium absorption in jejunum and cecum by 64% and 38%, respectively, by enhancing lumen-to-plasma calcium flux (CaL-P) in the jejunum and by reducing plasma-to-lumen flux (CaP-L) in the cecum. Since PRL-enhanced both CaL-P and CaP-L in the ileum, net calcium absorption did not change. In weaned rats, PRL significantly increased CaL-P in the jejunum but not in the ileum. However, the increase in net absorption was not significant. In contrast, effect of PRL was not seen in aged rats. By demonstrating an absence of PRL action on jejunal calcium fluxes when sodium-free test solution was used, we reconfirmed the sodium-dependent PRL action on passive calcium absorption. The PRL-induced parallel increase in the lumen-to-plasma transport of 45Ca and [3H]mannitol indicated that PRL action was to increase the paracellular transport of calcium.

Further studies on acute effect of prolactin on intestinal calcium absorption in rat

The present investigation aimed to (1) reconfirm the acute effect of prolactin on intestinal calcium absorption in the rat, (2) evaluate the influence of age on prolactin action, and (3) further investigate the mechanisms of prolactin action on calcium absorption. The intestinal calcium absorption in mature rats was evaluated by measuring the plasma 45Ca content at intervals during a 1-h period following intragastric administration of a 45Ca-containing test solution and by measuring tibial 45Ca content in weaned rats. By using weaned (50-70 g), sexually mature (180-200g) or aged (greater than 250 g) female Wistar rats, we demonstrated that calcium absorption was inversely related to age. Prolactin at a dose of 0.02 mg/100 g body weight, administered intraperitoneally 1 h before Ca administration, significantly enhanced calcium absorption in sexually mature and weaned rats but not in aged rats. At a luminal calcium concentration of 5 mM, prolactin had no effect when the luminal solution was either CaCl2 alone or an Na-free electrolyte solution. On the other hand, prolactin significantly increased the plasma 45Ca content by 57, 42 and 28% at 5, 15 and 30 min respectively, when the electrolyte solution contained sodium. In contrast, in the presence of 0.5 mM calcium, the enhancing effect of prolactin on calcium absorption was not dependent on the presence of sodium. Compared with the saline control, the plasma 45Ca content in prolactin treated animals was significantly elevated by 63% at 5 min when the test solution was a sodium-free electrolyte solution.

Biliary Calcium and Bile Acid Secretion in Intact and TPTX Rats with Varying Plasma Calcium Concentration

Investigations of the effects of plasma calcium concentration on the relationship between biliary secretion of bile acid and calcium were performed in normocalcemic, calcium gluconate-induced hypercalcemie, thyroparathyroidectomy-induced hypocalcemic (TPTX) rats, and TPTX rats that received calcium gluconate to maintain normocalcemia. Studies were done at normal bile flow and at sodium taurocholate-stimulated bile flow. The results showed that biliary calcium secretion, which could occur in the absence of parathyroid hormone and calcitonin, was dependent mainly on plasma calcium concentration and was only partly influenced by bile acid secretion. Concerning the route of biliary calcium secretion, 80% was by the transcellular pathway and 20% was by the paracellular pathway. During theophylline-stimulated bile-acid-independent bile flow, the increase in bile-acid-independent calcium was found to be secreted by both pathways.

The effects of xanthines on mouse liver cell

Abstract Pretreatment of mice with caffeine or theophylline for 3 days (100 mg/kg, intraperitoneally, twice daily) resulted in an increase in microsomal protein, RNA content, and cytochrome P-450 content. Caffeine but not theophylline also shortened the duration of action of pentobarbital in mice. Both xanthines, however, had no effect on the onset and duration of action of hexobarbital in these animals. Chemical measurements revealed that the activities of two drug-metabolizing enzymes, aminopyrine N-demethylase and p-nitroanisole O-demethylase, were markedly increased by this schedule of pretreatment with caffeine but slightly increased by theophylline. Further, it was found that the inductive effect of caffeine, but not of theophylline, was accompanied by complete depletion of glycogen granules in the liver and a high degree of proliferation of the smooth endoplasmic reticulum. This effect on glycogen depletion, which was followed by an elevation of blood glucose, may be the result of caffeine inhibition on hepatic phosphodiesterase, because the cyclic AMP content was more than doubled in caffeine-treated hepatocytes. It was concluded that the stronger stimulatory effect of caffeine on drug metabolism than theophylline might be attributed to a much more pronounced proliferation of hepatic endoplasmic reticulum caused by caffeine.

The Mechanism of Action and Target Organ of Gastrin-Induced Hypocalcemia

Abstract The hypocalcemic effect of gastrin and the possible role of the hormone in calcium homeostasis have been demonstrated in our previous study. The mechanism involves neither the gastrointestinal absorption nor the removal of calcium from plasma but is possibly due to the suppression of the calcium influx into blood. In searching for the organ(s) involved in the action of gastrin, the following were tested and not found to be directly responsible: stomach, intestine, pancreas, liver, spleen, adrenal gland, kidney, lung, muscle, and red blood cell. After 17 hr of 45Ca administration, the turnover of 45Ca in the tibia was measured. Gastrin was found to suppress the release of 45Ca by 25% within 1 hr. The suppressive effect of gastrin on 45Ca release was also demonstrated in an in vitro preparation which showed that the 45Ca released from prelabeled tibia into the incubating medium was also reduced by gastrin. It was thus concluded that the gastrin-induced hypocalcemia in rat was the result of a suppression of the release of calcium from bone.

The Influence of Gastrin on Plasma Calcium, Bile and Gastric Calcium Secretions in the Rat

Summary The influence of gastrin on calcium (Ca) homeostasis was investigated in anesthetized rats. When administered intraperitoneally, gastrin was found to lower plasma Ca concentration in both intact rats and rats which had their source of calcitonin removed (thyroparathyroidectomized) but to exert no significant effect on the rates of urine Ca excretion in the intact rats. Thus, its hypocalcemic effect was independent of calcitonin. In search of possible routes of Ca removal from the blood, both the Ca concentration in gastric juice and the total gastric Ca excretion were measured. Total gastric calcium excretion increased from 14 ± l.4 to 22 ± 2.4 μg/hr/100 g rat by the administration of gastrin. The increase in gastric Ca secretion and the hypocalcemic effect were abolished by concurrent administration of secretin (2 units). The bile volume and the Ca content in the bile secretion were not affected by gastrin. These findings were compatible with the hypothesis that the hypocalcemic effect of gastrin was partly caused by an increased Ca excretion into the gastrointestinal lumen.

Possible role and mode of action of gastrin on calcium homeostasis in the rat.

Abstract The hypocalcemic effect of gastrin and its possible mode of action were studied in rats. Gastrin (13 μg/100 g rat), injected intravenously led to a significant reduction in the plasma calcium concentrations. The release of endogenous gastrin by an intragastric phenylalanine instillation similarly led to a significant hypocalcemia in intact rat but not in antrectomized rat. Moreover, the protective role of endogenous gastrin against hypercalcemia induced by an intraduodenal infusion of CaCl2 (10 mg/100 g rat) was demonstrated. Gastrin (50 μg/100 g rat) seems to have no influence on the net intestinal absorption of 45Ca. The removal of 45Ca from plasma was also unaffected by gastrin administration. The disappearance rate from plasma of 45Ca administered 17 hr previously was compared in sham, thyroidectomized (TX) and parathyroid-auto transplanted rats receiving saline or gastrin. The faster rate of disappearance of plasma 45Ca from plasma in gastrin-treated TX autoparathyroid-transplanted rats indicated the suppressive action of gastrin on the release of 45Ca from as yet unknown source(s).

Environment and the ageing lung

Abstract A brief review of changes in the morphology, physiology and defence mechanism in the ageing lung is presented. During the ageing process, the lung is also affected by environmental insults, which can be exogenous or endogenous. Exogenous factors include infection, climate, air pollution and mechanical injuries, whereas endogenous environments are certain system diseases (e.g. diabetes mellitus and thromboembolism) as well as infectious diseases (e.g. tuberculosis).