The mechanism of catecholamine (CA) release evoked by transmural stumulation (TS) and action of some CA release inhibitors were studied. Isotonic contraction was used as an indicator of CA release. Results: 1) Contractions of TS, exogenous ACh and exogenous noradrenaline were respectively compared as regards influence of various drugs (Tables 1 and 2). 2) The following has been concluded: (1) Contraction of TS is due to stimulation of the hypogastric nerve (sympathetic nerve) ending, resulting in CA release from adrenergic fiber (AF) and ACh release from cholinergic fiber (CF) in this nerve. CA and ACh are related to the TS contraction in a ratio of approx. 6:4. (2) Intervention of ACh as proposed by Burn et al. is not indispensable for the CA release from AF under the influence of TS, however, endogenous ACh released from CF accelerates CA release. (3) Hexamethonium inhibits CA release of exogenous ACh, but not that of TS (and consequently that of endogenous ACh), while pempidine and mecamylamine inhibits both. (4) Bretylium inhibits irreversibly the release of both CA and ACh produced by TS, while inhibiting CA release of exogenous ACh less strongly and reversibly. 3) Against the TS contraction abolished by bretylium after washout, incubation with CA or ACh (followed. by washout) showed a temporary recovery, while that with calcium (followed by washout) resulted in a lasting recovery. Incubation with CA, ACh and calcium respectively restores the release of CA, of ACh and of both. It is suggested that bretylium blocks both AF and CF by competitive inhibition against the transmitters releasing action of calcium.
Two different types of monoamine oxidase (MAO) [EC 1. 4. 3. 4. monoamine: oxygen oxidoreductase (deaminating)], MAO-1 and MAO-2, were isolated and partially purified from beef liver by the procedure involving treatment of sodium cholate, 30_??_40% and 40_??_50% of ammonium sulfate fractionation, and chromatography of Sephadex G-50 and G-200. The specific activities of MAO-1 and MAO-2 were approx. 15-fold and 21-fold that of homogenate when tyramine was used as substrate. With n-butylamine as substrate, specific activities of both enzymes were different from that of tyramine. Enzymic properties of both enzymes were also studied, including pS maximum, optinal pH, substrate specificity, effects of various agents, such as p-methylphenylhydrazine (MPH), iproniazid (IIH), pheniprazine (JB-516), sodium nitrite and hydroxylamine. Results: 1) The pS maxima of various substrates for MAO-1 and MAO-2 were observed at the same concentration, but specific activities of MAO-2 at pS maxima of substrate examined were higher than those of MAO-1. 2) The pH optima of both enzymes with various substrates were observed at the same pH when tyramine and serotonin were used as substrates, but when β-phenylethylamine, benzylamine, n-amylamine and n-butylamine were used as substrates, different pH's were observed. 3) Substrate specificities of MAO-1 and MAO-2 were also studied. Both enzymes oxidized tyramine most rapidly. Moreover, MAO-2 oxidized n-butylamine, serotonin, n-amylamine, benzylamine and β-phenylethylamine in that decreasing order. MAO-1 slightly differed from that of the former enzyme in substrate specificity. 4) Both enzymic activities were inhibited by JB-516, MPH and IIH, however the degree of inhibition by addition of MPH or IIH differed between MAO-1 and MAO-2. In case of JB-516, the same degree of inhibition was'observed for both enzymes. 5) Difference in effects of the other agents, such as sodium nitrite activated MAO-1 activity, but did not affect MAO-2 activity. Hydroxylamine generally inhibited both enzymes, but MAO-2 activity was inhibited more strongly than MAO-1 activity.
1) Relaxations of periarterial nerve stimulation, nicotine (in the presence of atropine), tyramine, acetylcholine (in the presence of atropine and eserine) and calcium in the isolated rabbit's ileum have been investigated from the standpoint of catecholamine release phenomenon. 2) Periarterial nerve stimulation, nicotine and acetylcholine produce catecholamine release through mobilization of calcium. This calcium mobilization could be due to depolarization of sympathetic nerve ending membrane. Tyramine releases catecholamine by exchange reaction without mobilization of calcium. 3) The hypothesis of Burn et al. suggesting that catecholamine release by the sympathetic nerve stimulation is produced via the release of acetylcholine within this nerve cannot be accepted. 4) Nicotine releases catecholamine chiefly through the action of acetylcholine released from the parasympathetic nerve ending by the stimulation of parasympathetic ganglion. 5) Periarterial nerve stimulation, nicotine, acetylcholine and calcium release catecholamine from the same catecholamine store, while tyramine releases catecholamine from other stores.
Trihydroxyindole (THI) method for catecholamine assay was applied to fluorometric determination of isoproterenol, protokylol and α-methyl dopa. After procedure of THI formation, the fluorescence curve of these compounds shifted its peak to the direction of longer wave lengths and the intensity of fluorescence became approx. three-fold stronger as compared with the native fluorescence. Studies were carried out on stability, reaction specificity and recovery of fluorescent compounds formed in the procedure.
This report describes the tumor-inhibiting effect against Sarcoma 180 in mice of some wild and cultured Basidiomycetes. Results: 1. Some of wild and cultured Basidiomycetes preparations given intraperitoneally had an antitumor effect. Complete regression of the tumor was observed in many cases. 2. Both per- and post-treatment with PMS were effective, and a single injection of 100mg/kg with PMS was most effective. 3. Poly I: Poly C shows the tumor-inhibiting effect, however the effect was seen during the early stage of the tumor growth. 4. PMS was ineffective against Ehrlich ascites tumor in mice. 5. Acid mucopolysaccharides as Chondroitin sulfate was decreased an antitumor effect of PMS. 6. The intraperitoneal administration with PMS was most effective against spontane-ous mammary tumor in C3H/He mice.
From an analgesic screening test of 2-phenyl-3 (2H) pyridazinone derivatives, synthesized by Takahashi et al., 2-phenyl-4-dimetylaminopropylamino-6-ethoxy-3 (2H) pyridazinone hydrochloride (TM-3) was discovered to have pronounced analgesic activity. In the present paper, the pharmacological effects, particularly analgesic and anti-inflammatory effects of TM-3, are compared with those of aminopyrine (AP) or phenylbutazone (PB). 1) In an analgesic test using modified Haffner's method on mice, the potency of TM-3 was approx. 6 times that of AP. 2) The analgesic effect of TM-3 tested by electric stimulation, hot plate and acetic acid stretching methods was equal to or more potent than that of AP. 3) TM-3 showed an inhibitory effect similar to that of PB on carrageenin, yeast and dextran-indued edema of rat paws. 4) In dermal tissue permeability tests of rats, TM-3 exhibited an equal or more potent inhibition as compared to PB. 5) In Winter's cotton pellet granuloma test, TM-3 tended to inhibit granulation. 6) TM-3 showed an antipyretic effect comparable to that of AP on T. T. G. -induced rabbit fiver. 7) TM-3 exhibited an uricosuric effect on uric acid or adenine-induced hyperuricemic rats. 8) TM-3 did not exhibit anti-convulsive, muscle-relaxant or hypnotic effects and influenced slightly spontaneous respiration, blood pressure, EEG and isolated auricular movement of rabbits. 9) The acute and subacute toxicities of TM-3 were lower than that of AP and the safety margin of TM-3 as an analgesic agent was considerably higher than that of AP.
The effects of Coenzyme Q10 (CoQ10) on the development of experimental hypertension and its related conditions in unilaterally nephrectomized and Desoxycorticosterone acetate (12.5mg/kg i. m., weekly)-saline loaded rats were studied. Although 16 of the 17 control rats were hypertensive on the 6 th week, the incidence of hypertension in the groups receiving CoQ10 2mg/kg or 10mg/kg (p. o., daily) was 4 out of 16 and 2 out of 16 animals, respectively. At the end of 6th week, the following findings were detected in most of these experimental animals: a) ascites, increment of tissue fluid in the lung, increased extracellular fluid (SCN-space) in the whole body, lung and liver as well as a decrease in extracellular fluid in the heart, b) elevated Na+/K+ in plasma, c) increased weight of lungs, kidneys, adrenals and heart, d) morphologic changes such as hyaline degeneration in the myocardium, pulmonary congestion, centrolobular degeneration in the liver, fibrotic and hyalinized glomerulus, degeneration of tubular epithelia in the kidney, hypertrophic fasciculata and atrophic glomerulosa in the adrenals. Most of these changes were of slight degree in the animals treated with CoQ10 as compared with the controls. The possible mechanism of antihypertensive action of CoQ10 was discussed from the viewpoint that morphologic changes in the kidney and adrenal cortex were observed to be slight in the animals treated with CoQ10.
Physical, morphological and pharmacological studies of an experimental Whiplash Injury were done, using rabbits, to elucidate the injury mechanism and the effects of Pantui extracts, Pantocrin, on the injury. A device of rotary type, which is capable of producing concentrated exterior force effectively to the cervical region, was used to simulate experimental Whiplash Injury. The injured caput and cervical regions were physically, roentgenologically and pathologically examined and the requirement for producing Whiplash Injury of no serious damage was established, i.e., acceleration of 20G to the device and a weight of 300g an the rabbit head. In addition, a new method for optokinetic stimulation was employed to study nystagmus reactions on injured rabbits. Abnormally exaggerated patterns and lowered frequencies in the ENG were noted 3 to 21 days after the injury accompanying depressed glycolysis in cerebrospinal regions. Pantocrin, administered to the injured rabbits at an intramuscular dose of 1ml (ca. 1.5mg as a dry wt.) per kg daily from the 3rd to 21st day after injury, was markedly effective for improving the abnormalities in both ENG patterns and cerebrospinal glycolysis.
Using rabbits and rats injured in experimental Whiplash, changes in glycolysis and enzyme activities of the cervical cords, and the effects of Pantui extracts, Pantocrin were investigated in detail. In the cervical cords, depressed glycolysis and lowered activities of aldolase, GOT, and alkaline phosphatase were noted. Cervical injuries were greater in rats than rabbits while hexokinase, glycerokinase and GPT were inhibited. Three enzymes in the rabbits were also inhibited. This enzymological difference between the two species appeared to be dependent on the extent of injury. Pantocrin remarkably improved abnormal glycolysis and the lowered enzyme activities of cervical cords from both injured animals.