In reviewing recent progress concerning the motor system and drug action, the following subjects will be discussed on the basis of our data : 1) the mechanisms of action of mephenesin and baclofen, 2) baclofen and γ-aminobutyric acidB (GABAB) receptor, 3) GABA-, benzodiazepine receptors, 4) control of spinal motor system by descending noradrenergic neuron, 5) pharmacology of the muscle spindle, and 6) pharmacometrics of centrally acting muscle relaxants.
One of the major forms of cytochrome P-450, named P-450 HFLa, of human fetal livers was purified and characterized. The cytochrome P-450 preparation had an apparent molecular weight of 51500 as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. N-Terminal amino acid sequence of P-450 HFLa was similar but not identical to that of P-450NF involved in nifedipine oxidation in adult human livers. P-450 HFLa catalyzed 16α-hydroxylation of dehydroepiandrosterone 3-sulfate (DHEA-sulfate) in a reconstituted system. The concentration of P-450 HFLa in liver homogenates from human fetuses highly correlated with the activity of DHEA-sulfate 16α-hydroxylase. Furthermore, anti-P-450 HFLa antibodies inhibited the 16α-hydroxylation. P-450 HFLa was also found to catalyze the mutagenic activation of aflatoxin B1 (AFB1) and 2-amino-3-methylimidazo [4, 5-f] quinoline (IQ). The antibodies to P-450 HFLa inhibited efficiently the mutagen-producing activities from AFB1 and IQ in human fetal livers. The nucleotide and the deduced amino acid sequences of λHFL33 containing the entire coding region for a form of cytochrome P-450 related to P-450 HFLa, were highly similar to but clearly distinct from those of NF25 and HLp complementary deoxyribonucleic acids. The oligonucleotide probes specific to the coding and 3'-noncoding region of λHFL 33 (oli-HFL and oli-HFL3', respectively) gave hybridizable bands with ribonucleic acid (RNA) from fetal but not adult livers. In contrast, an oligonucleotide probe specific to the coding region of NF 25 and HLp (oli-NF) gave hybridizable bands with RNA from only adult but not fetal livers.
Since elucidation of structure of deoxyribonucleic acid (DNA) as genetic material, it was established that DNA makes ribonucleic acid, which makes protein according to the original information given in DNA base as base sequences. From these basic idea of genetic flow system there was emerged the word "protein engineering". According to this principle, engineering of h-lysozyme, RNase H and their relevant proteins was described. A triosephosphate isomerase barrel type protein was designed and expressed.
Physiological studies on inorganic ions were historically reviewed. Extremely asymmetric distribution of Ca2+ inside and outside the cell is the basis of its unparalleled role in intracellular processes. This must be rightly appreciated from the viewpoint of the origin of life, where the attention has exclusively been focused on the protein so far. Recognition of the importance of Ca2+ and other inorganic ions as the essential factor in these meanings may be a key for elucidating the strategy of the life.
Biological activities of the 50% ethanolic extract of Kijitsu, dried immature Citrus fruits prepared from C. hassaku HORT. ex TANAKA (H), C. natsudaidai HAYATA (N) or allied plants (T, A) were observed. Weak toxicities, weak intestine or uterine relaxant activities, β-adrenergic activities were shown by in vitro experiments and antiasthmatic activity by intraperitoneal administration. These activities among each extract did not differ. The content of flavonoids (narirutin, naringin hesperidin, neohesperidin) or synephrine did not show much difference among the four dried immature Citrus fruits. These results suggest that H can be used for medicine as the substitute for N, T or A which has been commonly used as Kijitsu. This method is generally applicable to the proof of the biological equivalency of the crude drug and its substitutes.
A study was carried out to clarify the active component of green fruit of Citrus unshiu MAKOVICH on the type I allergic reaction. The flavonoid component, isolated from its methanolic extract, hesperidin, was found to inhibit histamine release from peritoneal mast cells of rats induced by compound 48/80. Forty eight-hour homologous passive cutaneous anaphylaxis (PCA) in intact rats was significantly inhibited by the oral administration of hesperidin. However, the anti-allergic action on PCA was not observed in adrenalectomized rats. These results suggests that hesperidin is an effective component of the fruit of Citrus unshiu with the anti-allergic action against the type I reaction.
Sixty seven methanol extracts of crude drugs were examined for their effects to protect hepatic injury induced by α-naphthylisothiocyanate (ANIT) in rats. In terms of the release of intrahepatic enzymes and bilirubin into the serum, 19 extracts were found to suppress the increase in the concentration of serum bilirubin by ANIT. Out of the 19 extracts those of Berchemia Racemosa Caulis, Aurantii Nobilis Pericarpium, Polygoni Avicularis Herba and Gentianae Scabrae Radix, also inhibited the release of several intrahepatic enzymes used as parenchymal injury parameter.