The excitability of peripheral and central neurons is regulated by two types of ion channels, voltage- and ligand-operated ones. Recent studies have revealed that the activities of these ion channels are under the control of a variety of classical neurotransmitters and neuropeptides. In particular, certain ion channels such as voltage-dependent Ca and K channels are reciprocally regulated by excitatory and inhibitory neurotransmitters, leading to the excitation and inhibition of nerve cells : for example, 1) the activation of voltage-dependent K channel is facilitated by somatostatin and inhibited by substance P, and 2) the opening of voltage-gated Ca channel is augmented by substance P and suppressed by somatostatin and certain opioid peptides. The ligand-gated ion channel, nicotinic acetylcholine receptor is also controlled by the actions of neuropeptides, substance P and calcitonin gene related peptide (CGRP). The regulation of ion channels with neuropeptides may contribute not only to the control of neuronal excitability but also to the plasticity of the nervous system.
It is now widely accepted that the suprachiasmatic nucleus (SCN) of the hypothalamus is a circadian pacemaker in the mammalians. This conclusion is based on three principal lines of the following evidence. First, ablation of the SCN results in a loss of circadian rhythms in rodents. Second, the SCN exhibits rhythms in neuronal activity and glucose metabolism both in vivo and in vitro experiments. Third, the transplantation of fetal SCN to the third ventricle of animals rendered arrythmic by SCN ablation restores circadian function. In this review the anatomical, physiological and pharmacological characteristics of SCN neurons in vitro are discussed by foccusing especially upon the roles of various neurotransmitters and modulators in the circadian system of mammals, in relation to the function of SCN.
Bromohydrins (12, 13, and 14), which were oxidatively damaged products of thymidine nucleotides, were repaired by the action of sunlight (2700 lux) or heat via a radical mechanism to regenerate the original nucleotides (8, 9, and 10). A significant effect of 3', 5'-phosphate linkage on the repair reactions to natural type of thymidine nucleotide was proposed.
The effect of XKJ-001, a crude drug preparation based on Seisho-ekki-to, was investigated on the hematocrit, plasma volume, extracellular and interstitial fluid volumes as well as water excretion in mice. Mice were housed in an animal room maintained at 34°C for 3 d with water and food freely available. While the hematocrit, extracellular and interstitial fluid volumes increased, the plasma volume decreased. These results suggest that the distribution of body water in mice housed at high environmental temperature exhibit the state of water metabolism disorders (Suitai) described in Kampo medicine. After the administration of XKJ-001 (3 g/kg, once a day) for 5 d, mice were housed in an animal room maintained at 34°C for 3 d. The administration of XKJ-001 was allowed to continue on the day 0, day 1 and day 2. XKJ-001 inhibited the increase in hematocrit and the changes in body water distribution of mice induced by high environmental temperature. An effect of XKJ-001 on water excretion in mice was investigated in comparison with hydrochlorothiazide (HTZ). Distilled water (D.W., 100 ml/kg) or bicarbonate saline (B.S., 100 ml/kg) was intraperitoneally injected immediately after the oral administration of XKJ-001 (1.5 g/kg) or HTZ (15 mg/kg). The water excretion was enhanced after 3 h for XKJ-001 and after 6 h for HTZ after the intraperitoneal injection of D.W. As for the intraperitoneal injection of BS, HTZ enhanced the water excretion, however, XKJ-001 exhibited no effect. These results suggest that XKJ-001 has activities on water maldistribution and facilitates the water excretion.
Methanol extracts of 53 crude drugs were tested on the anticomplementary activity. Of these, 12 samples showed the potent activity. Of these 12 samples, the extract of Jozann (Dichrome Radix) was studied on the isolation and structural elucidation of the anticomplementary constituents. As active constituents, 3β-hydroxystigmast-5-en-7-one was isolated and its structure was confirmed by deriving this compound from β-sitosterol. The activity of such steroid derivatives as stigmastane, cholestane, androstane and pregnane type steroids were further studied. Of these, several kinds of steroids showed the potent activity. From these experiments, the structure and activity relationship was discussed.
Three steroidal saponins 3, 4 and 5a were newly isolated from Anemarrhenae Rhizoma. Compounds 3 and 4 were identical with desgalactotigonin and F-gitonin, respectively. Compound 5a was established as (25S)-26-O-β-D-glucopyranosyl-22-hydroxy-5β-furostane-3β, 26-diol 3-O-β-D-glucopyranosyl-(1→2)-O-β-D-galactopyranoside on the basis of chemical and spectroscopic evidence.
The roots and/or rhizomes of Glychyrrhiza uralensis, G. glabra and G. inflata, and commercial licorice specimens from various regions or countries were analyzed by high-performance liquid chromatography (HPLC), and classified into three types based on their phenolic constituents. i) Type A : The roots and rhizomes of G. uralensis, commercial licorice specimens from northwestern region of China (Seihoku-kanzo) and from northeastern region of China (Tohoku-kanzo) in Japanese markets, and also several licorice specimens from Chinese markets. They contain licopyranocoumarin (6), glycycoumarin (7) and/or licocoumarone (8), which were not found in G. glabra and G. inflata. ii) Type B : The root and rhizome of G. glabra, and the licorice specimens imported from the Soviet Union and Afghanistan. They contain glabridin (9) and glabrene (10), which were not found in the samples of the other two Glycyrrhiza species. A root sample of Glycyrrhiza species from Turkey also contains 9 and 10. iii) Type C : The root sample of G. inflata. They contain licochalcones A (11) and B (12), which were not found in the samples of the other two Glycyrrhiza species. Commercial licorice specimens obtained in Japan, which were imported from Sinkiang of China (Shinkyo-kanzo), and some licorice specimens obtained from Chinese markets, have also been found to contain 11 and 12. The phenolics 6-12, characteristic constituents of types A, B or C, were not found in a specimen of cortex-free licorice from a Japanese market (kawasari-kanzo). Extracts of some licorice specimens of types A and B, and all of the licorice specimens of type C inhibited 40-56% of the xanthine oxidase activity at the concentration of 30μg/ml. Extracts of some licorice specimens of types A and B also showed inhibitory effects on monoamine oxidase (44-64% inhibition, at the concentration of 30μg/ml), which were slightly weaker than that of harmane hydrochloride.
In order to develop a nontoxic radioprotector, 60 kinds of Chinese traditional medicines were chosen, and their aqueous extracts tested for their survival effects against the lethal effect of X-irradiation in mice. Radiation factors used were as follows : soft X-rays, 2100R (5.418×10-1Ckg-1), 70 kVp, 10 mA, 10 mm acrylic filter, 70R (1.806×10-2Ckg-1)/min. Among 60 medicines tested by intraperitoneal injection immediately before the irradiation, 15 are shown to have the significant survival effect. These 15 effective medicines were also tested by intraperitoneal injection after the irradiation, and the survival effect was recognized in Keisi-syakuyaku-chimo-to, Keigai-rengyo-to, Simotu-to, Syakuyaku-kanzo-to and Hange-syasin-to. On the other hand, the survival effects of 25 medicines including the above-mentioned 15 medicines were investigated by the oral administration at various times before or after the irradiation. As the result of these studies, only Keigai-rengyo-to and Bukuryo-in are shown to have the significant survival effect when administered 2 h before the irradiation.