Biomedical subjects

M Misawa

Publications and source records attributed to M Misawa.

At least 145 records · Page 8Linked to original sources

PubMed1993

Effects of rimcazole, a specific antagonist of sigma sites, on the antitussive effects of non-narcotic antitussive drugs.

We examined the effects of rimcazole, a specific antagonist of sigma sites, on the antitussive effects of dextromethorphan and noscapine in mice. Intraperitoneal injection of rimcazole, in doses from 1 to 10 mg/kg, significantly and dose dependently antagonized the cough depressant effect of N,N'-di(orthotolyl)guanidine (DTG), a sigma ligand. The cough depressant effects of dextromethorphan (3 mg/kg i.p.) and noscapine (10 mg/kg i.p.) were also significantly and dose dependently reduced by pretreatment with rimcazole. However, rimcazole (10 mg/kg i.p.) did not have a significant effect on the antitussive effect of morphine (3 mg/kg i.p.). Furthermore, rimcazole by itself (10 and 30 mg/kg i.p.) had no significant effect on the number of coughs. These results suggest that sigma sites may be involved in the antitussive mechanism of centrally acting non-narcotic antitussive drugs.

Animals↗

PubMed1993

Effects of serotonergic anxiolytics on physical dependence on diazepam in mice.

The effects of serotonergic anxiolytics on the development of physical dependence on diazepam were examined in mice. Co-administration of buspirone (5-HT1A agonist) or ondansetron (5-HT3 antagonist), but not mianserin (5-HT1C antagonist) or ketanserin (5-HT2 antagonist) with diazepam potentiated the hypersensitivity to FG 7142 following chronic treatment with diazepam. This potentiation was not ascribable to pharmacokinetic interactions between diazepam and buspirone or ondansetron. These results suggest that co-administration of buspirone or ondansetron with diazepam may potentiate the development of physical dependence on diazepam; 5-HT1A and 5-HT3 receptors may be partially involved in the development of physical dependence on diazepam.

Animals↗

PubMed1993

The effects of cyclosporine on morphine-induced antinociception in diabetic mice.

The effects of cyclosporine on the antinociceptive effect of morphine were examined in diabetic mice. Sensitivities to the antinociceptive effect of morphine (5 mg/kg s.c.) in diabetic mice which had been pretreated with cyclosporine (30 mg/kg per day s.c.) for 14 days returned to those in vehicle-treated nondiabetic mice. Naive mice which had been injected with the supernatant of spleen cell homogenate (SSCH) from vehicle-treated diabetic mice were less sensitive to morphine-induced antinociception. However, adoptive transfer of SSCH from cyclosporine-treated diabetic mice to naive mice had no effect on the recipients' antinociceptive sensitivities to morphine. These results suggest that the abnormal antinociceptive effect of morphine and the immune responses of diabetic mice may somehow be related.

Analgesics↗

PubMed1993

Effect of diabetes on the antinociceptive effect of beta-endorphin.

We examined whether streptozotocin-induced diabetes can modulate beta-endorphin-induced antinociception in mice. While beta-endorphin administered i.c.v. produced a dose-dependent inhibition of the tail-flick response in both diabetic and non-diabetic mice, the antinociceptive response was greater in diabetic mice than in non-diabetic mice. The ED50 value of beta-endorphin administered i.c.v. in diabetic mice was significantly lower than that in non-diabetic mice. The antinociceptive effects of beta-endorphin administered i.c.v. in both diabetic and non-diabetic mice were significantly antagonized by s.c. administration of naltrindole, a selective delta-opioid receptor antagonist. beta-Endorphin administered i.t. also produced a dose-dependent antinociception in both diabetic and non-diabetic mice. However, the ED50 value of kappa-opioid receptor antagonist. On the other hand, the antinociceptive potency of DPDPE, a selective delta-opioid agonist, administered i.t. is significantly increased in diabetic mice, as compared with non-diabetic mice, whereas, the antinociceptive potency of U-50,488H, a kappa-opioid receptor agonist, administered i.t. is significantly less than in non-diabetic mice. These results suggest that diabetes may modulate beta-endorphin-induced antinociception differently at the spinal and supraspinal levels.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1993

Modification of morphine-induced locomotor activity by pertussis toxin: biochemical and behavioral studies in mice.

The effect of pertussis toxin (PTX) on the locomotor-enhancing action of systemic and intracerebroventricular (i.c.v.) morphine was investigated in mice. Mice were i.c.v. injected with either PTX (0.25 and 0.5 micrograms) or saline as a control. The s.c. (5-20 mg/kg) and i.c.v. (7-30 nmol) administration of morphine produced a dose-related locomotor-enhancing action in control mice. The peak effect of morphine (30 nmol, i.c.v.)-induced hyperlocomotion was observed 90 min after the morphine injection. At the same time, morphine significantly increased dopamine (DA) metabolism in the limbic forebrain (nucleus accumbens and olfactory tubercle). Similarly, the selective mu-opioid receptor agonist [D-Ala2,N-MePhe4,Gly-ol5]enkephalin (DAGO, 4 nmol, i.c.v.) also significantly increased locomotor activity and DA metabolism in the limbic forebrain. Both morphine- and DAGO-induced hyperlocomotion and elevation of DA turnover were antagonized by pretreatment with the mu antagonist beta-funaltrexamine (beta-FNA). These results suggest that the locomotor-enhancing action of morphine results from the activation of central mu-opioid receptors, and that the activation of the mesolimbic DA system may be involved in the expression of morphine-induced hyperlocomotion in mice. Furthermore, pretreatment with PTX (0.5 micrograms, i.c.v., 6 days prior to the testing) significantly reduced hyperlocomotion and elevation of DA turnover in the limbic forebrain which had been induced by administrations of morphine (30 nmol, i.c.v.) and DAGO (4 nmol, i.c.v.). These findings suggest that the central PTX-sensitive GTP-binding protein (G-protein) mechanism may play an important role in opioids-induced locomotor-enhancing action. Furthermore, the activation of mesolimbic DA transmission by mu-opioid agonists may also be mediated by a PTX-sensitive G-protein mechanism in mice.

Analgesics↗

PubMed1993

The role of the mu 2-opioid receptor in the antitussive effect of morphine in mu 1-opioid receptor-deficient CXBK mice.

The effect of morphine on the capsaicin-induced cough reflex was studied in mu 1-opioid receptor-deficient CXBK mice. There was no significant difference between the morphine-induced antitussive effect in CXBK mice and C57BL/6 mice, a progenitor strain. Furthermore, the antitussive effects of morphine in both the CXBK and C57BL/6 mice were antagonized by pretreatment with either naloxone or beta-funaltrexamine, a mu-opioid receptor antagonist, whereas pretreatment with naltrexonazine, a selective mu 1-opioid receptor antagonist, had no effect. Moreover, naltrindole, a selective delta-receptor antagonist, also had no significant effect on the antitussive effects of morphine in either CXBK or C57BL/6 mice. These results support our previous hypothesis that mu 2- rather than mu 1-opioid receptors are involved in morphine-induced antitussive effects.

Animals↗

PubMed1993

Antitussive effects of mu- and kappa-agonists in diabetic rats.

We evaluated the antitussive effect of morphine and U-50,488 in diabetic and non-diabetic rats. The antitussive potency of morphine (0.3 mg/kg, i.p.) in diabetic rats was significantly reduced as compared to the results in non-diabetic rats. The antitussive effect of U-50,488, a kappa-agonist, was also significantly lower in diabetic rats than in non-diabetic rats. When naltrindole (0.03 mg/kg, i.p.), a delta-antagonist, was administered 15 min before morphine or U-50,488, there was no difference between the antitussive potencies of these two opioid agonists in non-diabetic rats and in diabetic rats. Furthermore, naltrindole produces a reduction of the number of coughs in diabetic rats, but not in non-diabetic rats. It is possible that the enhancement of the antitussive potency of morphine and U-50,488 in naltrindole-treated diabetic rats is the result of the antitussive synergy produced by these opioid agonists and naltrindole. It seems likely, therefore, that delta-receptor-mediated endogenous inhibitory systems in mu- and kappa-receptor-mediated antitussive processes may be activated under diabetic conditions.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1993

Antinociceptive effects of intrathecally administered endothelin-1 in mice.

Intrathecal administration of endothelin-1 (ET-1) produced dose-dependent antinociceptive effects in the tail-flick test. The antinociceptive effects of ET-1 were attenuated significantly by pretreatment with naloxone and the delta receptor-selective antagonist naltrindole. The antinociceptive effects of ET-1 were also significantly attenuated by pretreatment with verapamil, an L-type Ca(2+)-channel blocker. These results suggest that the mechanism underlying the antinociceptive effects of ET-1 involves mediation, at least in part, by Ca(2+)-induced release of endogenous opioids, which act on delta-opioid receptors.

Animals↗

PubMed1993

Differential modulation of mu-opioid receptor-mediated antitussive activity by delta-opioid receptor agonists in mice.

We examined the effect of [D-Ala2]deltorphin II, a selective delta 2-opioid receptor agonist, on the antitussive effect of [D-Ala2, MePhe4,Gly-ol5]enkephalin (DAMGO), a selective mu-opioid receptor agonist. [D-Ala2]deltorphin (3 nmol i.c.v.) had no significant effect on the number of coughs. However, upon i.c.v. pretreatment with [D-Ala2]deltorphin II (3 nmol) the antitussive activity of DAMGO (0.03 nmol) was significantly enhanced. The enhancement of the antitussive activity of DAMGO caused by [D-Ala2]deltorphin II was prevented by a benzofuran derivative of naltrindole (0.1 mg/kg s.c.), a selective delta 2-opioid receptor antagonist. These results suggest that delta 2-opioid receptors may play a synergistic role in antitussive processes that are mediated by mu-opioid receptors.

Animals↗

PubMed1993

Antitussive effect of beta-endorphin is mediated by mu-opioid receptors, but not by kappa- or epsilon-opioid receptors.

The present study examined the opioid receptors involved in the antitussive effect of beta-endorphin in mice. beta-Endorphin injected i.c.v. depresses coughs dose dependently in doses from 0.1 to 1 microgram. Blockade of mu-opioid receptors by pretreatment with beta-funaltrexamine significantly reduced the antitussive potency of i.c.v. beta-endorphin. However, the antitussive effect of beta-endorphin was not antagonized by nor-binaltorphimine, a kappa-opioid receptor antagonist. Moreover, i.c.v. injection of beta-endorphin-(1-27), an epsilon-opioid receptor antagonist, did not affect the antitussive effect of beta-endorphin. The results indicate that the antitussive effect of beta-endorphin is mediated by activation of mu-opioid receptors, but not of kappa- or epsilon-opioid receptors.

Animals↗

PubMed1993

Morphine-induced place preference in the CXBK mouse: characteristics of mu opioid receptor subtypes.

The role of mu opioid receptor subtypes, mu 1 and mu 2, in morphine-conditioned place preference was examined using ddY and mu 1 opioid receptor-deficient CXBK mice. In ddY mice, the mu receptor agonist morphine caused a dose-related preference for the drug-associated place, but the kappa agonist U-50,488H produced a dose-related place aversion. These results demonstrated that the mouse is available for place preference conditioning using opioids. Under this condition, the influence of pretreatment with the selective mu 1 opioid receptor antagonist naloxonazine on morphine-induced place preference was investigated in ddY mice. Although pretreatment with the selective mu 1 antagonist naloxonazine (35 mg/kg, s.c.) did not modify the morphine-induced place preference, pretreatment with the selective mu antagonist beta-funaltrexamine (beta-FNA 10 mg/kg, s.c.) eliminated the appetitive effect of morphine. Furthermore, morphine (1-5 mg/kg, s.c.) produced a dose-related preference for the drug-associated place in CXBK mice. These findings suggest that the morphine-induced conditioned place preference may be mediated by naloxonazine-insensitive sites (mu 2 opioid receptors). In addition, chronic infusion of the dopamine D1 antagonist SCH23390 (1.0 mg/kg/day) during the conditioning sessions eliminated the morphine-induced place preference in CXBK mice. Similarly, morphine combined with naloxonazine failed to produce the place preference in ddY mice chronically treated with SCH23390. The blocking effect of SCH23390 on the morphine-conditioned place preference suggests that mu 2 receptors may regulate the dopaminergic system, especially dopamine D1 receptors, and are also involved in the reinforcing effects of morphine.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1993

Possible involvement of mu 2-mediated mechanisms in mu-mediated antitussive activity in the mouse.

The effect of pretreatment with naloxonazine on mu-opioid agonist-mediated antitussive effects was studied in mice. The antitussive effects of [D-Ala2, MePhe4, Gly-ol5]enkephalin (DAMGO) and morphine were significantly antagonized by naloxone pretreatment, 1 mg/kg given i.p. 5 min earlier, but not by naloxonazine pretreatment, 35 mg/kg given s.c. 24 h earlier. In contrast, the antinociceptive effects of these mu agonists, as determined by the tail-flick method, were significantly reduced by pretreatment with both naloxone and naloxonazine. These results suggest that mu 2 rather than mu 1 mechanisms are involved in mu-mediated antitussive effects.

Analgesics↗

PubMed1993

Absence of bcr/abl gene in single hemopoietic progenitors in some patients with chronic myelogenous leukemia.

CD34+DR- and CD34+DR+ cells were isolated from the marrow mononuclear cells of five patients with chronic myelogenous leukemia (CML) carrying the Philadelphia (Ph) chromosome. Analysis of bcr/abl hybrid mRNA in individual colonies from a single cell using reverse transcriptase polymerase chain reaction (RT-PCR) demonstrated the presence or absence of the hybrid mRNA. For patient 1 in the chronic phase of CML, the hybrid mRNA was detected in all colonies derived from CD34+DR+ and CD34+DR- hemopoietic progenitors. In contrast, for patient 2 in the chronic phase of CML, the mRNA was detected in all individual colonies from CD34+DR+ progenitors but not in any from CD34+DR- progenitors. For patient 3 in the chronic phase of CML, the mRNA was detected in all individual colonies from CD34+DR+ but in only some of the colonies from CD34+DR- progenitors. For patients 4 and 5 in the acute crisis of CML, the mRNA was found in a portion of colonies from CD34+DR+ and CD34+DR- progenitors. These results indicated that normal clones can persist in CD34+DR- progenitors in some patients with CML, even when chromosome analysis detects the Ph chromosome in all metaphases of bone marrow cells.

Adult↗

PubMed1993

Effect of pretreatment with pertussis toxin on the development of physical dependence on morphine.

The effect of intracerebroventricular (i.c.v.) pretreatment with pertussis toxin (PTX) on the development of physical dependence on morphine was investigated in mice. Twenty four hours after PTX (0.5 microgram, i.c.v.) or vehicle pretreatment, the mice were chronically treated with morphine (8-45 mg/kg, s.c.) for 5 days. Several withdrawal signs were observed following naloxone challenge in morphine-dependent mice which had been pretreated with vehicle. In addition, 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) and noradrenaline (NA) turnover (MHPG/NA) levels in the cerebral cortex were increased following naloxone challenge in morphine-dependent mice. These findings indicate that activation of the central noradrenergic system may mediate the expression of some withdrawal signs. In contrast, pretreatment with PTX attenuated the naloxone-precipitated withdrawal signs in morphine-dependent mice. The incidence of withdrawal signs such as jumping, "wet dog" shakes, and rearing was significantly reduced by PTX pretreatment. PTX pretreatment also prevented the naloxone-precipitated increases in MHPG concentration and NA ratio (MHPG/NA) in the cerebral cortex, suggesting that central PTX-sensitive GTP-binding proteins (G-proteins) may be involved in the elevation of NA transmission in the cortex which projects from the locus coeruleus (LC) during morphine withdrawal. The blocking effects of PTX on the behavioral and biochemical changes after withdrawal suggest that central PTX-sensitive G-proteins (Gi/Go) may play an important role in the development of physical dependence on morphine.

Animals↗

PubMed1993

Airway inflammation induced by xanthine/xanthine oxidase in guinea pigs.

Airway inflammation is suggested to play an important role in bronchial asthma. However, there is poor documentation about the effects of reactive oxygens on airway tissues in aspect of airway inflammation. Presently, we investigated whether aerosolized xanthine (X)/xanthine oxidase (XOD) induces airway inflammation in anesthetized guinea pigs. Inhalation of X for 5 min followed by inhalation of XOD for 5 min was performed with an ultrasonic nebulizer in anesthetized animals. Airway inflammation was assessed by airway vascular permeability using Pontamine sky blue. Inhalation of X/XOD produced a marked Pontamine sky blue exudation in the trachea, main bronchus and lungs. The X/XOD-induced increase in Pontamine sky-blue exudation was attenuated by pretreatment with inhaled catalase, but not by superoxide dismutase. Additionally, in the bronchus and lungs, the increase in Pontamine sky-blue exudation was significantly suppressed by deferoxamine. The above results indicate that hydrogen peroxide and hydroxyl radical converted from superoxide anion cause an intense airway inflammation.

Administration, Inhalation↗

PubMed1993

Activation of central ATP-sensitive potassium channels produces the antinociception and spinal noradrenaline turnover-enhancing effect in mice.

ICV cromakalim, a K+ channel opener, produced antinociception. This effect was completely antagonized by ICV glibenclamide, a selective adenosine triphosphate-sensitive K+ channel (KATP channel) blocker. Furthermore, direct opening of central KATP channels by ICV cromakalim increased the spinal noradrenaline (NA) turnover. On the other hand, the antinociception induced by ICV morphine (mu opioid agonist), but not ICV U-50,488H (kappa opioid agonist) was markedly potentiated by cromakalim. These findings suggest that the opening of central KATP channels may elicit the antinociceptive effect and activate the descending NAergic pathway, and central KATP channels play an important role as a modulator of the antinociception induced by mu agonists but not kappa agonists.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1993

Delta-opiod receptor-mediated forced swimming stress-induced antinociception in the formalin test.

Forced swimming stress-induced antinociception (FSSIA) was assessed using the formalin test. Male ICR mice, weighing about 30 g, were forced to swim in water at 20 degrees C for 3 min. In unstressed mice, SC injection of formalin (0.5%) to the hindpaw caused a biphasic response: an immediate nociceptive response (first phase) followed by a tonic response (second phase). Although forced swimming stress (FSS) had no effect on the duration of the first-phase response, FSS significantly reduced the duration of the second-phase response. The effect of FSSIA on the second-phase response was blocked by naltrindole (1 mg/kg, SC), a selective delta-opioid receptor antagonist, but not by beta-funaltrexamine (20 mg/kg, SC), a selective mu-opioid receptor antagonist. These results indicate that FSS may selectively reduce the second phase of the formalin-induced nociceptive response, primarily through delta-opioid receptors.

Animals↗

PubMed1993

An ATP-sensitive potassium channel blocker abolishes the potentiating effect of morphine on the bicuculline-induced convulsion in mice.

ICV bicuculline, a selective GABAA antagonist, dose-dependently induced clonic-tonic convulsions in mice. Coadministration of ICV morphine (mu opioid agonist) significantly potentiated ICV bicuculline-induced convulsions, and this effect of morphine was completely blocked by pretreatment with beta-funaltrexamine (beta-FNA), a mu antagonist. ICV glibenclamide, a selective ATP-sensitive potassium (KATP) channel blocker, at a dose which alone did not affect the convulsive threshold of bicuculline, was capable of blocking the exacerbation of ICV bicuculline-induced convulsions by morphine. The present data further suggest that KATP channels may play a tonic regulatory role in the potentiative effect of morphine on ICV bicuculline-induced convulsions.

Adenosine Triphosphate↗