L-Dopa Potentiates Presynaptic Inhibitory α2-Adrenoceptor- but Not Facilitatory Angiotensin II Receptor-Mediated Modulation of Noradrenaline Release from Rat Hypothalamic Slices

Abstract

ABSTRACT-The effects of menatetrenone, a vitamin K2 homologue, on bone loss induced by ovariectomy in rats were studied in 3 experiments. Menatetrenone was given as a dietary supplement. In experiment 1, at 2 weeks postovariectomy, menatetrenone (10 mg/kg/day given for 2 weeks) inhibited the decrease in bone density of the femoral metaphysis induced by the ovariectomy. In experiment 2, menatetrenone (3 or 30 mg/kg/day given for 6 months) inhibited the decrease in bone strength of the femur and the decrease in calcium and hydroxyproline content of the femoral diaphysis at 6 months postovariectomy. In experiment 3, menatetrenone treatment, at 30 or 100 mg/kg/day for 6 months, protected against the decrease in bone strength and calcium and hydroxyproline content in the bone loss model induced by ovariectomy and calcium-deficient diet. These findings suggest that menatetrenone protects against the bone loss induced by ovariectomy. Keywords:Menatetrenone, Ovariectomy, Bone lossSince Bouckaert and Said first reported the effect of vitamin K on fracture healing in 1960 (1), several studies have suggested that this vitamin affects bone metabolism. Hall et al. reported that some infants whose mothers had received oral anticoagulant therapy during pregnancy had hypoplasia of the nasal bone (2). Hart et al. demonstrated that circulating levels of vitamin K, in osteoporotic patients with fractures were significantly lower than those in age-matched control subjects (3). It is well-known that vitamin K is essential for the r-carboxylation of osteocal cin (4), a non-collagenous protein present in bone (5, 6). Although the role of osteocalcin in bone metabolism remains obscure, it is possible that vitamin K may play a role in bone metabolism via this substance.Two types of vitamin K occur in nature: vitamin K, (phylloquinone, 2-methyl-3-phytyl-1,4-naphthoquinone), which is derived from plants, and vitamin K2 (menaqui nones), a series of vitamers with multi-isoprene units at the 3-position. In the present studies, we assessed the effects of menatetrenone (2-methyl-3 -all-trans-tetra prenyl-1,4-naphthoquinone), a vitamin K2 with four isoprene units, on bone loss induced by ovariectomy in rats in three different experiments: In experiment 1, we examined its effects on early metaphysial bone loss in the femur; in experiment 2, we studied its effects on the de velopment of bone loss induced by ovariectomy over a 6-month period; and in experiment 3, we studied its cura tive effects over 6 months on bone loss induced by ovariec tomy and a calcium-deficient diet. MATERIALS AND METHODS AnimalsFor experiment 1, we used 20-week-old female Fischer rats (Clea Japan, Inc., Tokyo); and for experiments 2 and 3, we used 40-week-old female Sprague-Dawley rats (Charles River Japan, Inc., Tokyo). The animals were housed in a room maintained at 261C with a 12-hr light dark cycle and were given free access to food and distilled water. All operations were performed under pentobar bital anesthesia. Experiment 1Twenty rats underwent bilateral ovariecto...

Effects of Menatetrenone on the Decrease in Calcium Balance Induced by Vitamin K-Deficient Diet and Sodium Loading in Rats.

“…The use of a coumarin-related vitamin K an tagonist during pregnancy was found to cause character istic nasal hypoplasia or stippled epiphysis (3). A vitamin K2 homologue, menatetrenone (MK-4), was shown to be effective in ameliorating bone loss induced by ovari ectomy in rats (4), and the clinical efficacy of MK-4 was demonstrated in a double-blind multi-center comparative study with alfacalcidol in patients with postmenopausal and senile osteoporosis (5). Vitamin K, prevented in creases in urinary calcium excretion in rats that received vitamin K-deficient feed and antibiotics (6) and in postmenopausal women (7).…”

Menatetrenone Ameliorates Reduction in Bone Mineral Density and Bone Strength in Sciatic Neurectomized Rats

“…Recent clinical studies have suggested that MK-4 effectively prevents the occurrence of new frac tures in patients with postmenopausal osteoporosis (6 -8) and ameliorates osteoporosis associated with Parkin son's disease (9). The effects of MK-4 on bone metabo lism were demonstrated in a model of postmenopausal osteoporosis (10)(11)(12). It is generally accepted that bone resorption is increased in ovariectomized rats.…”

“…It is generally accepted that bone resorption is increased in ovariectomized rats. Various studies have suggested that MK-4 prevents, to some extent, the bone loss induced by ovariectomy by inhibit ing bone resorption (10,11). We reported that MK-4 protected against the loss of trabecular bone volume and its structure in rats rendered osteoporosic by sciatic neurectomy, through the process of maintaining bone formation (13 Three weeks after neurectomy, six neurectomized rats (SNx) and six sham-operated rats were sacrificed to obtain pre-administration data (day 21).…”

“…MK-4 (menatetrenone; Eizai Co. Ltd., Tokyo, Japan) was given as a dietary supplement 30mg/100g, 85mg/100g of the diet, respectively. The dosages of MK-4 were set based on the results of earlier studies (10,12,13 Bone mineral densitometry (BMD). At the designed determination points, bone samples were taken and all the connective tissues were carefully removed.…”

Oral Administration of Cal K2 Containing Menaquinone-4 (Vitamin K2) Enhances Serum r-Carboxylated Osteocalcin and Biochemical Components in the Femoral Tissues of Rats

“…[9][10][11] Menaquinone-4 (MK-4) with four isoprene units has been shown to have a preventive effect on bone loss induced in rats by ovariectomy. [12][13][14] MK-4 is used as a therapeutic tool for osteoporosis. The effects of the supplemental intake of MK-4, however, have not been fully clarified.…”