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Biomedical subjects

K Kisara

Publications and source records attributed to K Kisara.

At least 163 records · Page 9Linked to original sources

[Effects of intra-arterially administered capsaicinoids on vocalization in guinea pigs and medial thalamic neuronal activity in cats (author's transl)].

Algesic actions of capsaicinoids were investigated by utilizing vocalization in conscious guinea pigs and medial thalamic neuronal activity in gallamine triethiodide immobilized cats. Intra-arterial administration of capsaicin and dihydrocapsaicin evoked strong vocalization response, but other capsaicinoids, nordihydrocapsaicin, homodihydrocapsaicin, homocapsaicin, norcapsaicin, N-(4-hydroxy-3-methoxybenzyl)-6-methylheptamide, and N-(4-hydroxy-3-methoxybenzyl)-6-methylhept-trans-4-enamide, were weaker than capsaicin and dihydrocapsaicin. Similar results were obtained from medial thalamic nociceptive neurons in cats. Morphine (10 mg/kg s.c.) suppressed vocalization response evoked by intra-arterial administration of capsaicin and bradykinin. Aspirin (100 mg/kg i.p.) also suppressed the bradykinin-evoked response, but not the capsaicin-evoked response. Capsi-amide, a non-pungent substance of Capsicum annuum L., failed to suppress nociceptive response to capsaicin or bradykinin in guinea pigs and cats. Tachyphylaxis was elicited by repeated administration of capsaicin in vocalization. No cross-tachyphylaxis to bradykinin, acetylcholine, and dihydrocapsaicin could be observed.

Action Potentials↗

Effect of cyclic dipeptides containing histidine on pentobarbital narcosis.

We examined the effect of cyclo (His-Pro) and its analogs on pentobarbital narcosis in mice. Cyclo (His-Pro), 500 nmol/mouse, administered via intracerebroventricular (i.c.v.) route significantly prolonged the sleeping time. Methylation of histidine in the structure of cyclo (His-Pro) did not increase the activity of cyclo (His-Pro). Some of other cyclo (His-Pro) analogs, of which proline was replaced with other amino acids, cyclo (His-Phe), cyclo (His-Tyr), cyclo (His-His) and cyclo (D-His-Leu) produced significant prolongation of the sleeping time as compared with cyclo (His-Pro). These results suggest that cyclo (His-Pro) has opposing effect to that of thyrotropin releasing hormone (TRH) and the prolongation of pentobarbital narcosis by cyclic dipeptides might be caused by their central action.

Animals↗

Effects of intracerebroventricular administration of aliphatic diamines on ingestive behavior in the rat.

We examined the pharmacological effects of intracerebroventricularly administered aliphatic diamines on ingestive behavior in male rats adapted to a 4 hr per day feeding and drinking schedule. 1,2-Ethanediamine (ETD), 1,3-propanediamine (PRD), 1,4-butanediamine (putrescine, PUT), 1,5-pentanediamine (cadaverine, CAD) and 1,6-hexanediamine (HED) suppressed feeding and drinking behavior in a dose-dependent manner, but not unless a relatively high dose (over 80 micrograms) was given. The approximate anorectic potency was HED greater than CAD divided by PUT greater than ETD greater than PRD. A sedation was also produced in fairly good parallel to these alterations in feeding and drinking behavior. Thus, there appears to be a relationship between the length of the carbon chain and the potency of the pharmacological action, and these inhibitory effects on feeding and drinking behavior are probably not due to a specific action on the regulatory system for ingestive behavior, but rather to a nonspecific action.

Animals↗

Changes in ingestive behavior, serum glucose and free fatty acids concentrations in rats following intracerebroventricular injection of spermine.

We examined the changes in ingestive behavior, serum glucose (Glc) and free fatty acids (FFA) concentrations in male rats following intracerebroventricular (i.c.v.) injection of spermine (SPM). In satiated rats, over a 53.3 nmol of SPM suppressed feeding and drinking behavior in a dose-dependent manner. The median suppressive dose was 90.8 nmol for feeding behavior and 68.3 nmol for drinking behavior. Spermidine also suppressed ingestive behavior but the potency was appreciable weak compared to that of SPM, and the occurrence of the maximal suppression was observed 2-3 days later than that of SPM. The most significant anorexia and adipsia induced by SPM appeared between 16 and 36 hr after i.c.v. administration. SPM (180 nmol) produced a biphasic increase in serum Glc concentration. The 1st peak was at 1 hr and the other peak was 24 hr after the dosing. The same dose of SPM elevated serum FFA concentrations gradually, and the maximal increase appeared 24 hr after the injection. As less than a 120 nmol dose of SPM did not alter serum Glc and FFA concentrations, there seems to be no causal relation between SPM-induced anorexia, and changes in serum Glc and FFA concentrations. Nevertheless, the findings that a very small dose of SPM produced anorexia and adipsia support the possibility that SPM may play some functional role in the brain.

Animals↗

[Effects of parasympathetic drugs on head-twitch response induced by tyramine (author's transl)].

We investigated the effects of various parasympathetic drugs on the head-twitch response (HTR), as induced by intracerebroventricular (i.c.v.) administration of tyramine in mice pretreated with safrazine, a monoamine oxidase inhibitor. Intraperitoneal administration of neostigmine, methacholine, carbamylcholine, methylatropine or hexamethonium did not alter the HTR induced by tyramine. The i.c.v. infusion of acetylcholine, physostigmine, nicotine, carbamylcholine or atropine slightly inhibited the tyramine-response. The i.c.v. infusion of pilocarpine, methacholine, mechamylamine, hexamethonium or tetraethylammonium resulted in a slight or significant potentiation of the HTR. These results suggest that the HTR induced by tyramine is accelerated by mechanisms related to muscarinic receptors within the central nervous system and that the tyramine-response is suppressed by mechanisms related to nicotinic receptors.

Animals↗

[Effects of intraperitoneally administered spermine on ingestive behavior, serum glucose and free fatty acids concentrations in rats (author's transl)].

The intraperitoneal administration of spermine (SPM) produced a dual-phasic feeding suppression. The first suppression appeared immediately after the administration and disappeared on the 2nd day. The next suppression was observed on the 3rd day and continued for 2-4 days. The 50% dose which induced suppression on the 3rd day was 64.9 (60.9-69.2) mumol/kg. Drinking behavior was also suppressed on the 1st day, but was facilitated on the 2nd day and lasted for 4-5 days. Serum glucose and free fatty acids concentrations increased after the administration of SPM (80 mumol/kg). Their maximal values obtained at 3 hours after the dosing were 116% and 156% of the control values, respectively. These increases in both substances were not observed in the adrenal-demedullated rats. The same dose of SPM enhanced serum glutamic oxaloacetic transaminase and glutamic pyruvic transaminase activities. The maximal values obtained at 2 hours after the dosing were 264% and 142% of the control values, respectively. On the contrary, serum cholinesterase activity decreased to 44% of the control value at the same hour. These variations of the enzyme activities disappeared at 3 hour, but were again observed between the 1st and 4th days. The results suggest that SPM releases catecholamines from the adrenal medulla, and exerts a toxic action on the liver. The anorexia induced by SPM may be due to these actions on the viscera.

Alanine Transaminase↗

Head-twitch response induced by tyramine.

The intracerebroventricular (IC) administration of tyramine (TyA) induced a characteristic head-twitch response in mice pretreated with safrazine, a monoamine oxidase inhibitor. Safrazine-pretreated mice exhibited similar head-twitches following the IC treatment of serotonin (5-HT). The maximum dose of 5-HT which did not elicit head-twitches significantly potentiated TyA-induced head-twitches. Antiserotonergic drugs such as morphine and dimethothiazine antagonized TyA-induced head-twitches. A serotonergic denervator, 5,6-dihydroxytryptamine, potentiated head-twitch induced by TyA or 5-HT. Both TyA-induced and 5-HT-induced head-twitches were inhibited by dopamine and noradrenaline, while catecholaminergic denervators such as reserpine and 6-hydroxydopamine, and diethyldithiocarbamic acid, a dopamine-beta-hydroxylase inhibitor, increased the TyA response. These results indicate that head-twitches induced by TyA may be mediated via the serotonergic system and may inhibit the catecholaminergic system.

5,6-Dihydroxytryptamine↗

A simple determination of serotonin, 5-hydroxyindoleacetic acid and 5-hydroxytryptophan decarboxylase activity in rat brain areas and parallel correlation among the levels.

We devised a simple method for the separation of serotonin (5HT) and 5-hydroxyindoleacetic acid (5HIAA) using small P-cellulose and DEAE-Sephadex columns, respectively. Both substances were estimated fluorometrically by the reaction with o-phthalaldehyde (OPA). In this method, some known interfering substances in addition to many primary amines and amino acids were separated from 5HT and 5HIAA. The recoveries of 5HT and 5HIAA were 80 and 71%, respectively. The fluorescence intensities of 30 pmol of 5HT and 15 pmol of 5HIAA were about twice over the reagent blank. The complete separation of 5-hydroxytryptophan (5HTP) from 5HT made it possible to determine 5HTP decarboxylase activity in rat brain areas without using an isotope-labeled substrate. The method allows for quantitation of the enzyme activity in mg amounts of the brain tissues. The activities in discrete areas were in good parallel with the 5HT contents, except for the striatum. The levels of 5HIAA were also much in parallel with those of 5HT.

Animals↗

Effects of morphine on evoked potentials recorded from the amygdala by tooth pulp stimulation in cats.

Effects of intravenously administered morphine on the evoked potentials of the amygdala elicited by tooth pulp stimulation were examined in cats. The various evoked potentials were observed in regions of the amygdala such as nucleus amygdaloideus centralis (pars lateralis), nucleus amygdaloideus basalis (pars magnocellularis), nucleus amygdaloideus basalis (pars parvocellularis) and nucleus amygdaloideus lateralis. Evoked potentials were significantly decreased by morphine in four of the recorded regions. Morphine had no effect on the latency at any site of the amygdala observed. Depressant effects of morphine on evoked potentials were antagonized by naloxone in all 14 cats. This study indicates that there is a receptive field of pain in the amygdala which undoubtedly plays a role in emotion.

Amygdala↗

Excitatory effects of dihydrocapsaicin on nociceptive neurons in the medial thalamus.

Effects of capsaicin and dihydrocapsaicin, which are pungent substances contained in Capsicum annuum L., were studied in 32 gallamine triethiodide immobilized cats. Single units were recorded from the medial thalamus using stainless steel microelectrodes. Of the 56 neurons recorded, 28 were responsive to both noxious (pinching) and non-noxious (hair and/or tapping) stimuli, while 16 were activated only by non-noxious stimuli. The remaining 12 neurons did not respond to any natural stimulus. Somatic receptive fields of nociceptive and non-nociceptive neurons were found to be widely distributed over the whole body. Twenty-six of 28 nociceptive neurons were activated by an intra-arterial administration of bradykinin, capsaicin and dihydrocapsaicin. Fourteen of 16 non-nociceptive neurons were not activated by these substances. The mean latency and duration of bradykinin were 8.7 and 12.5 sec, those of capsaicin were 1.2 and 6.1 sec and those of dihydrocapsaicin were 1.3 and 5.0 sec, respectively. The increase of firing frequency produced by capsaicin and dihydrocapsaicin was inhibited by morphine and this inhibition was antagonized by naloxone. However, the activity of medial thalamic neurons with non-noxious stimuli was not affected by these drugs. These results suggest that the pain-conducting fibers were selectively activated by capsaicinoids as well as by bradykinin.

Action Potentials↗

[The effect of thiamine deficiency on the actions of drugs affecting the central nervous system in rats (author's transl)].

Male Wistar rats, 35-days-old, maintained on a thiamine deficient diet for 30 days showed marked growth inhibition and a heart rate less than 70% of that of control rats. We examined the effect of thiamine deficiency on the action of drugs effecting the central nervous system at this period. In thiamine deficient rats treated with chloral hydrate 200 mg/kg, ketamine 100 mg/kg sodium pentobarbital 50 mg/kg, and hexobarbital 100 mg/kg, the sleeping time increased. Pretreatment with 15 mg/kg of the metabolic enzymes inhibitor, SKF-525A, 30 min prior to the hexobarbital administration resulted in prolongation of sleeping time in all groups. The thiamine deficient rats slept almost 3.5 times longer than did the control group. Pretreatment with 100 mg/kg of the metabolic enzyme inducer, sodium phenobarbital, 48 hours prior to hexobarbital treatment resulted in decreased sleeping time in all groups, as compared with only hexobarbital treatment. In the thiamine deficient rats the catalepsy and ptosis induced by the i.p. administration of tetrabenazine 50 mg/kg was reduced even when the control and pair-fed groups responded to this drug at the drug peak time. The spontaneous neuronal activity of lateral hypothalamus was most sensitive to the administration of 5-hydroxytryptophan in thiamine deficient rats.

5-Hydroxytryptophan↗

[Studies on the effects of thiamine deficiency on rat testes (author's transl)].

Using male rats fed a thiamine deficient diet from the age of 35-days, an investigation was made of the effects on testicular tissue after 30 days of thiamine deficiency. It was found that: 1) In the thiamine deficient group, the seminiferous tubuli of rats having erections had atrophied and there was a decrease in the number of primary spermatocytes and spermatogonium, but a moderate increase in the number of sertoli cells. Furthermore, spermatids and spermia were rarely seen in tubuli which contained multinuclear giant cells. In the group of rats not having erections, moderate interstitial edema was seen and there was notable degeneration and reduction in the number of primary spermatocytes and spermatogonium. 2) In the group injected with thiamine hydrochloride after 21 days of thiamine deficient feeding, moderate interstitial edema was seen and the seminiferous tubuli were atrophic. 3) In the pair-fed group, there was a marked edema of interstitial tissue and an atrophy of seminiferous tubulus. 4) With regard to the effects of thiamine deficiency on the polyamine contents of the testicles, there was a marked decrease in spermidine content on the 12th day of feeding and a marked increase of spermine content on the 30th day. The spermidine/spermine ratio, which is high during periods of active cell differentiation and proliferation, was found to be significantly decreased in the thiamine deficient animals on both the 12th and 30th days of thiamine deficiency. Thus, it was clarified that thiamine deficiency causes disturbances in cell differentiation and proliferation in rat testes.

Animals↗

[Interaction of d-pseudoephedrine with water soluble extracts of Platycodi Radix on acute toxicity (author's transl)].

Effect of various combinations of Platycodi Radix water soluble extracts (Pla), 1-ephedrine (1-eph), d-pseudoephedrine (d-pseudo) and Ipecacuanhae Radix water soluble extracts (Ipe) on acute toxicity were examined in mice. Oral LD50 of Ipe, d-pseudo and 1-eph was 490 (415--578) mg/kg, 1550 (1360--1767) mg/kg and 1400 (1102--1778) mg/kg, respectively, while that of Pla was over 10 g. LD50 of Pla Ipe, d-pseudo and 1-eph given intraperitoneally was 1400 (1228--1596) mg/kg 235 (210--263) mg/kg, 245 (229--262) mg/kg and 300 (259--348) mg/kg, respectively. The ratio of the predicted LD50 value, which was calculated on the assumption that each component drug would be additively toxic when combined, to the observed LD50 value was used for comparison. The combination of d-pseudo with Pla gave a significantly greater LD50 value than the predicted LD50 value, while the combination of 1-eph with Pla showed a LD50 value which was not significantly different from Finney's additive model. A combination of d-pseudo with 1-eph and Ipe, and of 1-eph with Ipe showed a LD50 value which was not significantly different from that of the additive model.

Animals↗

[Effects of d-pseudoephedrine on tracheo-bronchial muscle and the cardiovascular system (author's transl)].

The action of d-psuedoephedrine on bronchial smooth muscle, respiratory resistance and blood pressure was compared with that of 1-ephedrine. The following results were obtained. 1) Administration of dl-isoproterenol on isolated guinea pig tracheal muscle previously constricted with acetylcholine (ACh) or histamine (his) was the most effective and d-pseudoephedrine had the same effect as 1-ephedrine. The relaxing effect of dl-isoproterenol, 1-ephedrine or d-pseudoephedrine on ACh or His induced tracheal constriction was competitively antagonized by the pretreatment of propranolol. 2) The intravenous or sublingual administration of d-pseudoephedrine on the increased respiratory resistance induced by His produced the same effect as 1-ephedrine. 3) The increase in blood pressure with d-pseudoephedrine was weaker than that of 1-ephedrine. 4) When 1-ephedrine of d-pseudoephedrine was repeatedly injected into the same animal, signs of tachyphylaxis were observed. It was found that d-pseudoephedrine, the main alkaloid of Ephedrine Helba, exhibited the relaxing effect on bronchial smooth muscles as did 1-ephedrine. The respiratory resistance increased by His was inhibited by the sublingual administration of d-pseudoephedrine and 1-ephedrine.

Administration, Oral↗

[Effects of diazepam on rage reaction elicited by the lateral hypothalamus (LH) and on single unit activities in the LH and the basal medial amygdaloid nucleus (Abm) in cats (author's transl)].

Effects of diazepam were examined on the whine reaction elicited by LH stimulation and on unit activities in the LH and Abm in cats. The spontaneous firing frequency of Abm neurons was 5 to 30 spikes/sec and in all 6 neurons isolated the firing frequency increased by non-nociceptive and/or clap-stimulation. Diazepam decreased the spontaneous firing frequency of all Abm neurons isolated and the increased firing frequency elicited by non-nociceptive and/or clap-stimulation was also depressed by diazepam. The spontaneous firing frequency of neurons in the LH was 4 to 5 spikes/sec and all 6 neurons isolated firing frequency increased by non-nociceptive stimulation. Only one of 6 neurons, however, was activated by clap-stimulation. Diazepam decreased the spontaneous firing frequency of all LH neurons. Out of 6 neurons responsive to non-nociceptive stimulation, 3 were also depressed by diazepam. The other neurons were not affected by diazepam. These results suggest that depressed action of diazepam on the whine reaction elicited by the LH stimulation may be related to the decrease of firing in the Abm and/or the LH by diazepam.

Amygdala↗

[Effects of diethyldithiocarbamate on ejaculatory inhibition and change in monoamine levels of accessory glands (author's transl)].

Effects of diethyldithiocarbamate(DDC) on erection and ejaculation were investigated and monoamine levels in central nervous system, gonad and accessory glands were determined in dogs. Intraperitoneal administration of 50, 75 and 100 mg/kg of DDC suppressed ejaculation 1 hour after administration, although penial erection did occur. This suppression of ejaculation was recovered to some extent 3 hours after DDC and completely recovered 24 hours after DDC. One hour after the administration of 100 mg/kg of DDC, noradrenaline (NA) level in the caudate and serotonin (5-HT) level in the posterior hypothalamus decreased significantly, as compared with the control. However, there were no significant changes in the regions of anterior hypothalamus and hippocampus which are known to play an important role in sexual behavior. In the epididymis, NA and adrenaline levels decreased significantly, though 5-HT levels increased, as compared with those of the control. In the prostate and posterior urethra, NA levels decreased significantly, as compared with the control. The seminal emission induced by hypogastric nerve stimulation induced a gradual rise in the posterior urethral pressure. When the pressure reached the maximum level, rhythmic alterations of the pressure considered to be a phenomenon associated with ejaculation occurred. DDC (100 mg/kg) abolished both seminal emission and rhythmic alterations of the posterior urethral pressure. These findings indicate that the sperm transport may be inhibited by decrease of NA level in accessory glands.

Amines↗