1) Catecholamine (CA) release from isolated bovine adrenal medullary granules suspended in isotonic KCl medium was stimulated by Ca++ or ATP·Mg.++ Low concentration of Ca++ may participate in the action of ATP·Mg.++ 2) The activity of Mg++-ATPase and DA-βS-hydroxylase in the granules was increased under the conditions which caused the release of CA from the graules by Ca++ or ATP·Mg.++ There appears to be close correlation between these enzyme activities and the rate of release of CA from the granules. 3) CA release from adrenal medullary slices was stimulated by serotonin, histamine and tyramine. However the stimulatory effects of these amines on CA release from the slices was observed both in the presence or absence of Ca++ in the incubation medium. 4) Cyc lic AMP and dibutyryl cyclic AMP have also stimulatory effects on the release of CA from the slices. However, the release of CA from the granules was not stimulated by these agents. Cyclic AMP was found to increase the rate of release of CA from the granules by ATP·Mg.++ Therefore it was suggested that cyclic AMP also play a role in the CA release from adrenal medulla by serotonin, histamine and tyramine. 5) Basing on these results, a working hypothesis of CA release from isolated adrenal medullary granules was represented.
In the Chinese medicine, Scutellaria baicalensis GEORG has been used as a remedy for some of allergic diseases. Therefore, the authors investigated the effects of baicalin and baicalein, components of the drug, on active anaphylactic reaction in guinea pig, and the results obtained were compared with those of rutin, methylhesperidin and quercetin. 1) By the administration of baicalin, the onset of preconvulsion caused by the antigen-aerosol in actively sensitized guinea pig was delayed about 3 times in contrast to the control, and the effect of baicalin was more potent than that of rutin. 2) Baicalin and baicalein inhibited Schulz-Dale reaction in isolated ileum, and the intensity of inhibition was following order; in glycoside, baicalin>rutin>methylhesperidin, and in aglycon, baicalein>quercetin. Futhermore, the effect of aglycone was more potent than that of each glycoside. 3) As the antigen was added to the organ bath which placed sensitized and non-sensitized ileum, sensitized ileum strongly contracted followed by contraction of non-sensitized one. In this condition, baicalin decreased the contraction of non-sensitized ileum, while baicalein strongly decreased those of both ones. 4) Baicalin and baicalein slightly showed antihistaminic and anticholinergic effects on ileum of guinea pig. 5) The antigen-antibody combination was not affected by baicalin or baicalein in ring precipitation test. 6) The release of histamine and SRS-A from sinsitized guinea pig lung which perfused with antigen were decreased by baicalin, and the decreasing activity was more remarkable than that of rutin. 7) Baicalin and baicalein inhibited the anaphylactic release of histamine and SRS-A from chopped tissue of guinea pig lung. There was not much difference between the inhibitory activities of them in a equal molar concentration. However, they neither affected the destruction of mediator released nor inhibited contraction of ileum by mediator. The inhibitory action of baicalein on release of mediator was not affected by the addition of Ca++, but decreased by cysteine.
In rats, repeated administration of barbital was shown to cause a marked decrease in the duration of pentobarbital narcosis. Attempts were made to examine whether the tolerance occurs as a result of a decreased sensitivity of the brain mechanism to the effects of pentobarbital or as a result of an increase in the rate of metabolism or an alteration in uptake and/or efflux of the drug by the brain tissues. In rats tolerant to pentobarbital, the rate of disappearance of the drug from the plasma or brain was more faster than that in non-tolerant rats, suggesting an increase in the metabolism of the drug. On the contrary, brain- and plasmaconcentrations of pentobarbital at the end of narcosis were significantly higher in tolerant rats than those in non-tolerant rats, suggesting the involvement of some type of neuronal adaptation referred to as cellular tolerance. Ability of the brain slices to take up 14C-pentobarbital or 14C-Aminoisobutyric acid was not affected by repeated administration of barbital to the animals.
Norbormide, [5-(α-hydroxy-α-2 pyridylbenzyl)-7-(α-2 pyridylbenzylidene)-5-norbornene-2, 3-dicarboximide] is selectively toxic to the genus Rattus and its LD50 iss 5-10 mg/kg. It dose not produce significant changes in species other than the rat and its LD50 are more than 1 g/kg. Norbormide caused elevation of blood pressure in rats at the dose less than 1 mg/kg, while caused fall of blood pressure in dogs and rabbits at the dose of 10 mg/kg. The cause of death in rat by Norbormide are significat constriction and loss of tension of wall of peripheral blood vessels in organs.
In the previous paper, the authors reported about the action of baicalin and baicalein on active anaphylaxis. In the present series of experiments, the action of these substances on passive anaphylaxis was examined and the following results were obtained. 1) The symptom caused by passive systemic anaphylaxis (PSA) was inhibited by emamined substances. In glycoside, the inhibitory effect of baicalin was more potent than those of rutin and methylhesperidin, and in aglycone, baicalein was more potent than quercetin. Furthermore, the effect of aglycone was more potent than that of corresponding glycoside. 2) The inhibitory effect of examined substances on PSA in guinea pigs was more effective in the case of administration at 2 hrs prior to challange than in that at 2 hrs and 24 hrs by dividing into two equal parts. 3) On the PSA in mice, all examined substances sligtly showed inhibitory effect. 4) By the intraperitoneal administration of examined substances, passive cutaneous anaphylaxis (PSA) in guinea pigs was inhibited in the following order; baicalein>rutin>baicalin≈methylhesperidin>quercetin>control. And also inhibited by the intradermal administration combined with antiserum, but the order of inhibition was shifted as follows; baicalein>methylhesperidin>quercetin>rutin>baicalin≈control. 5) The cutaneous response induced with histamine was inhibited by the examined substances in the following order; baicalein>baicalin≈rutin>methylhesperidin≈control>quercetin.
Depressor effect of bietaserpine was gradually observed in the conscious rabbits in a dose of more than 5 mg/kg i. v. With the blood pressure depression, negative chronotropic effect, slight decrease of lectal temparature and myosis were observed by the bietaserpine administration. Except such a high dose of bietaserpine as 40 mg/kg i. v., no diarrhea was witnessed in rabbits. With a moderate dose of bietaserpine (25 mg/kg, s. c.), complete disappearance in the duodenum and moderate decrease of catecholamine fluorescence both in the seminal vesicle and vas deferens were observed without affecting the serotonin distribution in those organs (Falck & Owmans method). Depressor mechanism of bietaserpine was suggested as similar to that of syrosingopine.
When an isolated rabbit-ear is perfused with its blood, the administration of bradykinin causes vasodilatation and increased outflow. This effect of bradykinin is entirely opposed to the results indicated in the perfusion with Ringers solution. The unkown vasoactive substances included in serum reverse the vascular action of bradykinin from constriction to dilatation. This phenomenon can be reproduced by means of adding the well known vasoconstrictive substance such as adrenaline to Ringers solution as perfusate. Since the venous system is always contracted with bradykinin, the arterial system must exceed the venous system in responce for bradykinin to show increased oufflow. When bradykinin causes the vasodilating action, blood celles may promote the rate of increase of oufflow probably through the loss of mechanical resistence to the vascular bed. The optimum pressure and pH of perfusate is also one of the conditions as to increased outflow with bradykinin.
A strip of rabbit aorta was incubated in Krebs bicarbonate solution. Contraction of aortic strip induced by barium chloride was markedly potentiated by pretreatment with ouabain. The ouabain potentiation of contraction by barium was completely abolished either in calcium-deficient medium or by excess of potassium in medium. Extreme lowering of sodium concentration in medium also abolished the ouabain potentiation of Ba-induced contration. The potentiation of contraction was not affected by lack of glucose in medium. Aorta isolated from the reserpinized rabbit also showed the same response to barium and ouabain as aorta of the normal rabbit. From the results obtained, it is evident that the ouabain potentiation of Ba-induced contraction of aorta is not related with catecholamine storage of blood vessel muscles but affected by change in calcium and potassium ions in medium.
The effects of colistin salts and its derivatives, such as colistin sulfate (C-S), colistin tartrate (C-T), colistin pantothenate (C-P) and sodium colistin methanesulfonate (C-M), on the blood pressure in dogs were investigated and following results were obtained. Colistin salts caused marked and sustained fall in blood pressure. Among them, C-S showed the most marked effect. C-M showed very week effect compared with the others. Marked tachyphylaxis was seen on the depressor effect by the repeated administration. Histamine-like substances in blood in dog by the administration of colistin salts were quantified. The quantity of them was the most when it produced maximum fall in blood pressure. The effect of colistin salts on the blood pressure in rabbits was the same as that of histamine.