The effect of capsaicin-sensitive nerve degeneration (capsaicin-treatment) on the corpus and the antrum was investigated in the absolute ethanol-induced lesion model in rats. The gastric lesions in the antrum were significantly aggravated by the capsaicin-treatment, while those in the corpus were not affected. To clarify the different susceptibility between the antrum and the corpus, the effects on gastric mucosal blood flow (GMBF), mucus secretion and levels of calcitonin gene-related peptide (CGRP) or substance P (Sub P), were investigated by the hydrogen gas clearance method, histochemical methods and immunohistochemical methods, respectively. The GMBF in the antrum was significantly decreased by the capsaicin-treatment, but that in the corpus was not. Moreover, capsaicin-treatment increased the mucus secretion in the antrum, but not in the corpus. Capsaicin-treatment significantly decreased CGRP and Sub P-immunoreactive substances in the vascular smooth muscle in the antrum, but not in the corpus. On the 4th day after absolute ethanol, antral ulcers were observed. From the above results, it was suggested that capsaicin-treatment decreased the gastroprotective ability in the antrum to a greater extent than in the corpus and this may be caused by the decrease of GMBF through the decrease of CGRP- and Sub P-immunoreactive substances.

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The effects of intrathecal noradrenaline (NA) on the flexor reflex mediated by group II afferent fibers (group II flexor reflex) were investigated in anesthetized spinal rats. Low doses (0.01 and 0.1 μmol) of NA-HCl inhibited the group II flexor reflex, while high doses (1 and 10 μmol) facilitated it. In rats pretreated with the selective α₂-antagonist yohimbine-HCl (0.1 μmol), the effect of NA-HCl (0.1 μmol) shifted from inhibition to facilitation. Intravenous administration of prazosin-HCl (0.1 and 1 mg/kg, i.v.), a selective α₁-antagonist, dose-dependently antagonized the facilitation of the group II flexor reflex induced by NA-HCl in rats pretreated with yohimbine-HCl. The selective α₂-agonist methoxamine-HCl (1 μmol) and the α₂-agonist clonidine-HCl (0.1 μmol) facilitated and inhibited the group II flexor reflex, respectively. The effects of clonidine-HCl and methoxamine-HCl were almost the same as those of NA-HCl at doses of 0.1 and 10 μmol, respectively. NA-HCl (1 and 10 μmol) and methoxamine-HCl(1 μmol) increased the spontaneous electromyogram (EMG) spikes of the muscle tibialis anterior. The time course of the increase in the spontaneous EMG spikes was similar to that observed in the group II flexor reflex. These results suggest that NA facilitates and inhibits the group II flexor reflex via α₁- and α₂-receptors, respectively, and one of the mechanisms of the facilitatory effects is the elevation of excitability of the α-motoneuron.

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The inhibitory effects of emedastine difumarate on histamine release were studied in rat peritoneal mast cells. Emedastine significantly inhibited substance P (SP)-induced histamine release at concentrations above 10^-9 M in the presence of extracellular Ca²⁺ and at concentrations above 10^-11 M in its absence. At concentrations of 10^-8 M or higher, emedastine significantly inhibited SP-induced Ca^2- release from intracellular Ca stores and SP-induced ⁴⁵Ca uptake into mast cells. Emedastine also inhibited passive peritoneal anaphylaxis in rats and guinea pigs. We conclude that the clinical antiallergic effects of emedastine involve the inhibition of histamine release and that this inhibition is mediated by the inhibition of Ca²⁺ release from intracellular Ca stores and the inhibition of Ca²⁺ influx into mast cells.

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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.

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To determine the effects of the Kampo drugs Saiboku-to, Bakumondo-to and Orengedoku-to on β-adrenergic function in airway smooth muscle, we studied isolated canine bronchial segments under isometric conditions in vitro. Incubation of tissues with these drugs did not alter the contractile responses to acetylcholine and histamine. The relaxation of tissues precontracted with acetylcholine induced by isoproterenol was augmented by Saiboku-to and Bakumondo-to, so that the concentration of isoproterenol required to produce a half-maximal effect (IC₅₀) was decreased from 4.6±0.5 × 10^-8 M to 1.9± 1.0 × 10^-8 M (P<0.05) and to 1.0±0.8 × 10^-8 M (P<0.01), respectively, whereas Orengedoku-to had no effect. These effects were concentration-dependent with the threshold concentrations being 0.3 mg/ml for Saiboku-to and 0.1 mg/ml for Bakumondo-to. Saiboku-to and Bakumondo-to did not affect cyclic AMP levels in airway smooth muscle per se but potentiated the isoproterenol-induced cyclic AMP accumulation. These results suggest that Saiboku-to and Bakumondo-to but not Orengedoku-to potentiate β-adrenergic function in airway smooth muscle, which may reflect the efficacy of these drugs on airway hyperresponsiveness and asthma.

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