The present study was undertaken in order to examine whether ceruloplasmin, tyrosinase and AgNO₃ change 5-HT into the pigment in vitro. The effects of 2, 3-Dimercaptopropanol (BAL) and α-MSH on the pigment formation from 5-HT was also studied. As a comparative study, the pigment formation from noradrenaline was also studied. 1) When noradrenaline was incubated with tyrosinase, the browish black pigment was formed. BAL inhibited this pigment formation, but α-MSH did not affect it. 2) The incubation of 5-HT with tyrosinase, α-MSH, or with both of them did not produce the pigment. 3) When 5-HT was incubated with AgNO₃ or with ceruloplasmin, the brown or the brownish black pigment was formed from 5-HT respectively. BAL inhibited the both types of pigment formation from 5-HT. α-MSH had no effect on the pigment formation from 5-HT by ceruloplasmin.

View full abstract

The assesment of analgesic action of narcotic antagonists by their ability to block the response of rat to retrograde intra-arterial injection of bradykinin was first reported by Blane. Authors have reconfirmed the technique and data of Blane and compared with data obtained using the mouse antiwrithing test.
Authors have concluded that the bradykinin-induced response was more specific and suitable for measuring analgesic effects of narcotic antagonists than anti-writhing method. It was also shown that the nociception induced by bradykinin was not mediated through the release of biogenic amines.

View full abstract

In the intact rabbit, 0.1 μg of bradykinin administered into the saphenous vein caused a constriction of both artery and vein and a decrease of venous flow in the ear with a depression of blood pressure. In these experiments the vasoconstriction following bradykinin may have had a variety of causes other than direct action. 0.1 μg of bradykinin administered into the central artery of the ear caused a vasodilatation and an increase of venous flow.
In the isolated rabbit ear preparations and guinea pig hindguarters, the perfusion pressure influenced venous outflow responses to bradykinin. Venous outflow was also influenced by the concentrations of bradykinin. Lower concentrations of bradykinin and higher perfusion pressure induced an increase in outflow and higher concentrations of bradykinin and lower perfusion pressure induced a decrease. The arterio-dilatation and venoconstriction were observed in isolated rabbit ear.
The direct action of bradykinin on the vessels is considered to be arterio-dilatation and venoconstriction. However, in certain preparations and under certain circumstances, bradykinin causes diverse action on the vessels. It is suggested that in the experiments in which the direct action is not observed, this action may be latent.

View full abstract

Pain pathways from the tooth pulp to the somatosensory cortex and the effects of morphine and barbiturate on the cortical responses evoked by the stimulation of the pulp were investigated electrophysiologically in rats. 1) Responses to the tooth pulp stimulation (contra- and ipsilateral) were recorded from the somatosensory face area I (SI) and II (SID. Latency of the response in SII was longer than that in SI. The latencies of the ipsilateral responses in SII were 2.5-3.0 msec longer than those of the contralateral responses and the ipsilateral responses were eliminated by acute ablation of the opposite cortex including SI and SII. 2) Although the contralateral responses in SI were significantly depressed by morphine (2.5, 5 and 10 mg/kg i. p.), the depression did not depend on the dose of morphine. The ipsilateral responses were significantly emphanced by morphine (5 and 10 mg/kg). 3) The contra- and ipsilateral responses in SII were significantly depressed by morphine and these depression depended on the dose of morphine. 4) The contra- and ipsilateral responses in SI and SII were essentially unchanged by pentobarbital sodium (4, 8 and 16 mg/kg), but the ipsilateral responses were enhanced. 5) All responses except the ipsilateral surface positive response in SI were significantly depressed by a high dose of pentobarbital sodium (32 mg/kg). The results obtained suggest that this somatosensory face area II and the pathway to this area from the tooth pulp may play an important role in the mechanism of pain.

View full abstract

In vitro and in vivo studies on the absorption of TSP from rat intestine were carried out using ¹³¹I-labelled TSP. Sac of everted rat jejunum was placed in TSP containing Krebs-Ringer's bicarbonate buffer, and a significant quantity of caseinolytic activity was detected in the serosal fluid. ¹³¹I-TSP was administered in a loop of rat intestine, and the radioactivity was found in various organs including blood. ¹³¹I-bound substances in the blood serum, collected from the mesenteric vein, was analyzed by Sephadex gelfiltration, etc. Experimental results revealed the presence of ¹³¹I-bound protein in the serum of ¹³¹I-TSP received rats, whereas such ¹³¹I-protein was hardly found in the control ¹³¹I-KI received rat serum. Thus the possibility of the absorption of TSP through the intestine was also discussed.

View full abstract

The actions of bradykinin and the influences of several drugs on them were investigated on the isolated spontaneous beating and electrically driven atria of guinea pigs.
Results : (1) Bradykinin produced an increase of heart rate and myocardial contractile force. These actions were dose dependent. 2) The positive chronotropic and inotropic actions of bradykinin were not influenced by reserpinization or by administering α- and β-adrenergic blocking agents. Therefore, bradykinin was considered to possess a direc cardiac stimulating action. 3) Homochlorcyclizine, pyridinolcarbamate and diphenhydramine depressed the positive chronotropic action significantly, but did not affect the positive inotropic action of bradykinin. 4) Histamine did not relate to the cardiac action of bradykinin.

View full abstract

The contraction of isolated guinea-pig ileum produced by phenyl acetate in the presence of choline was hardly inhibited by tetrodotoxin, adrenaline, cocaine and strychnine. Hemicholinium-3 which was reported to inhibit the ACh synthesis was effective in some degree. The sensitivity of ileum to phenyl acetate was retained without retiring after it had been stored at 2°C for 48 hrs without oxygen suppley, but when temperature of organ bath was lowered (cooled) at 13°C, the response of ileum to phenyl acetate in the presence of choline was slightly reduced.
From these results, it seems that this response is mediated by ACh which may be formed from phenyl acetate and choline by other mechanisms different from the ACh liberation in the ileum.

View full abstract

In the previous papers, the authors reported that brain monoamine oxidase (MAO) activity of the rat fed with high sucrose diet was increased in a state of formalin stress and decreased in the reserpine induced distress. Therefore, a study was taken to determine the alterations of related enzymatic activity and its substrate (5HT) in the rat under homeostatic state failed surgically and the effects on addition of several stressors in above chemical parameters and experimental condition.
1) Chronic administrations of ACTH or cortison enhanced the brain MAO activity in intact rats.
2) Adrenalectomy produced a decrease of above enzymatic activity in rats.
3) Such hypoactivity in adrenalectomized rat was also intensified with successive intramuscular injections or formalin while inhibited with chronic administrations or cortison or ACTH.
4) Above surgical and drug treatments did not exhibit any change in brain serotonin content.

View full abstract

The author examined the effects of glucuronolactone upon the sleeping time induced by thiopental sodium in the guinea pigs. The results obtained were as follows;
1) Premedication of glucuronolactone which was injected at 1 hour before the administration of thiopental sodium or the simultaneous injection of glucuronolactone with thiopental sodium shortend apparently the sleeping time induced by thiopental sodium. How ever, the injection of glucuronolactone at 2 hours before the administration of thiopental sodium did not exert such effects at all.
2) Thiopental sodium contents in the brain, the liver, the kidney and blood of the glucuronolactone-administered guinea pigs decreased gradually more than those in control guinea pigs which was administered thiopental sodium alone.

View full abstract

A new method for the measurement of uric acid in rat serum was studied. It involvus the isolation of uric acid by ion-exchange separation and automatically quantitative determination of uric acid in the elute by 287mμ absorption. The apparatus isJLC-2A-BC2 type of Japan electron optics laboratory co, LTD.. The condition of measure-ment is followed, stationary phase AG 50W×8 (200-400 mesh), mobil phase 0.5 N-HCL, flow rate 0.76 ml/min, separation column 0.8∅×50cm (35°C), paper speed 60 cm/hr.By this method the rat serum uric acid was measured authentically and continuously every 30 minutes without influence of coexistent substance. A series of determinationsof uric acid in rat serum compares well with determinations on the same samples using the colorimetric Eichhorn method. This method is seemed to be significant for the authentic measurement of serum uric acid.

View full abstract

Changes of serum uric acid level by the successive administrations of thiazide diuretics and other drugs in rats and effects of uricosuric drugs in these rats were studied and the following results were obtained.
1) On the serum uric acid level in normal rats, allopurinol and ketophenylbutazonehad significantly decreasing effect, but bucolome and probenecid had weak decreasing effect.
2) On the serum uric acid level in acutely uric acid loaded rats, allopurinol, ketophenylbutazone, probenecid and bucolome had significantly decreasing effect, but sulphinpyrazone and chinophene had not steady effect.
3) The hyperuricemia was induced by successive subcuteneously administrations of chlorothiazide, hydrochlorothiazide, adenine or uric acid for 2 weeks in rats.
4) On the hyperuricemic rats explained above, allopurinol had strong and regular decreasing effect of serum uric acid level by the single dose of 100 mg/kg i. p. or successive administrations of 50 mg/kg i. p. for last 1 weeks. Ketophenylbutazone and bucolome had also significantly decreasing effect, but whether probenecid, phenylbutazone and sulphinpyrazone had weak decreasing effect or not.
5) The strong decreasing effect of serum uric acid level of allopurinol on the acutely uric acid loaded rats or hyperuricemic rats which induced by successive admini-strations of uric acid suggest the other mechanisum in addition to xanthine oxidase inhibition of allopurinol.

View full abstract

Pharmacological properties of methylscopolam monium methylsulfate (MM) have been examined in comparison with those of butylscopolam monium bromide (BB). Antiacetylc-holineactivity of MM is particularly higher than that of BB although MM possesses also antihistamine, antinicotine, and antiserotonin actions. However, MM does not exhibit the cervical sympathetic ganglion-blocking action in doses of 5 mg/kg (i. v.) or less, while this action of BB is remarkable even in a dose of 3 mg/kg (i. v.) in cats. The curare-like action of MM is also weaker than that of BB. This compound is more potent than BB in dilating the pupil (mice) and in inhibiting the salivary flow elicited by pilocarpine (rabbits). In addition, the effects of MM on cardiovascular and central nervous system are discussed.

View full abstract