Biomedical subjects

M Misawa

Publications and source records attributed to M Misawa.

At least 163 records · Page 9Linked to original sources

PubMed1993

Differential modification of the rewarding effects of methamphetamine and cocaine by opioids and antihistamines.

We previously reported that the reinforcing effects of opioids are enhanced in combination with antihistamines. In the present study, effects of opioids and antihistamines on the reinforcing effects of psychostimulants such as methamphetamine and cocaine were investigated by utilizing the conditioned place preference procedure in rats. The place preference induced by methamphetamine was enhanced in combination with either morphine or chlorpheniramine, which produced additive and potentiative effects, respectively. In contrast, although the preference for cocaine was also enhanced by combination with these two drugs, morphine caused a potentiative effect and chlorpheniramine an additive one. In other words, the reinforcing effect of methamphetamine was differentially enhanced by opioids and antihistamines as compared to that of cocaine. These results suggest that the mechanism of reinforcing effect of methamphetamine is different from that of cocaine, resembling rather those of opioids.

Animals↗

PubMed1993

The effect of chronic treatment with naltrindole, a selective delta-opioid antagonist, on mu-opioid receptor-mediated antinociception in diabetic mice.

The effects of chronic treatment with naltrindole (NTI), a selective delta-opioid receptor antagonist, on the antinociceptive effects of mu-opioid agonists, such as morphine and [D-Ala2, N-MePhe4, Gly-ol(5)]enkephalin (DAMGO) were examined in diabetic mice. Antinociception induced by morphine (10 micrograms, ICV) and DAMGO (0.5 microgram, ICV) was significantly lower in diabetic mice than in non-diabetic mice. The low sensitivities to the antinociceptive potencies of ICV morphine (10 micrograms) and DAMGO (0.5 micrograms) in diabetic mice were reversed compared with those in saline-treated non-diabetic mice when diabetic mice had been pretreated with NTI (2 mg/kg per day, SC) for 14 days. Naive mice which had been injected with spleen mononuclear cells from saline-treated diabetic mice were less sensitive to DAMGO-induced antinociception. However, adoptive transfer of spleen mononuclear cells from NTI-treated diabetic mice to naive mice had no effect on the recipients' antinociceptive sensitivity to DAMGO. These results suggest that the effect of NTI on the sensitivity to mu-opioid agonists in diabetic mice may be due to the immunosuppressive effects of NTI.

Analgesics↗

PubMed1993

Antagonism of the morphine-induced Straub tail reaction by kappa-opioid receptor activation in mice.

The Straub tail reaction (STR) induced by intracerebroventricular injection (ICV) of morphine was significantly antagonized by beta-funaltrexamine (beta-FNA, mu antagonist), given intracerebroventricularly (ICV), but not naltrindole given ICV (NTI, delta antagonist) or SC norbinaltorphimine given subcutaneously (SC) (nor-BNI, kappa antagonist). When given either SC or ICV the kappa-agonist, U-50,488 H markedly suppressed the STR elicited by ICV morphine; these effects were reversed by nor-BNI. These results suggest that the activation of supraspinal kappa receptors can inhibit the ICV morphine-induced STR which results from activation of supraspinal mu receptors.

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

PubMed1993

Involvement of delta-opioid receptors in the effects of morphine on locomotor activity and the mesolimbic dopaminergic system in mice.

Naltrindole (NTI) and naltriben (NTB), a benzofuran derivative of NTI, were recently synthesized as highly selective delta-opioid receptor antagonists. Both NTI and NTB failed to suppress the antinociceptive effect induced by morphine. In contrast, both NTI and NTB significantly suppressed the morphine-induced hyperlocomotion and increase in turnover of dopamine (DA) in the mouse limbic forebrain. These results suggest that delta-opioid receptors play, at least in part, a role in the morphine-induced hyperlocomotion and excitation of mesolimbic DA systems, but not antinociception.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1993

Cold water swim stress inhibits the nociceptive responses to intrathecally administered somatostatin, but not substance P.

The effects of cold water swim stress (CWSS) on the nociceptive responses to i.t. administered substance P (SP) and somatostatin (SST) were examined. Male ICR mice, weighing about 30 g, were forced to swim in water at 20 degrees C for 3 min. In unstressed mice, i.t. injection of SP (0.1 nmol) and SST (1 nmol), respectively, produced nociceptive-related behaviors. Although CWSS had no effect on the intensity of the SP-induced nociceptive responses, CWSS significantly reduced the intensity of the SST-induced nociceptive responses. The effect of CWSS on the SST-induced nociceptive responses was blocked by naloxone (5 mg/kg, s.c.) and naltrindole (1 mg/kg, s.c.), a selective delta-opioid receptor antagonist, but not by beta-funaltrexamine (20 mg/kg, s.c.), a selective mu-opioid receptor antagonist. These results indicate that CWSS may selectively reduce the SST-induced nociceptive responses primarily through delta-opioid receptors.

Animals↗

PubMed1993

Blockade of the morphine-induced increase in turnover of dopamine on the mesolimbic dopaminergic system by kappa-opioid receptor activation in mice.

Activation of central mu opioid receptors by treatment with systemic morphine elevates 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) levels without changing dopamine (DA) and 5-hydroxytryptamine (5-HT: serotonin) steady-state levels in the mouse limbic forebrain (including nucleus accumbens and olfactory tubercle). Pretreatment with systemic U-50,488H, a selective kappa agonist, could dose-dependently block the morphine-induced increase in turnover of DA. This blocking action by treatment with U-50, 488H was completely reversed by nor-binaltorphimine (nor-BNI), a selective kappa antagonist. On the other hand, U-50,488H did not affect the enhancement of 5-HT turnover induced by morphine. These findings suggest that kappa receptor activation can inhibit the mu agonist-induced activation of mesolimbic DA pathway but not ascending 5-HT pathway.

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

PubMed1993

Effects of Ca2+ channel blockers on physical dependence on diazepam in mice.

The effects of Ca2+ channel blockers on the development of physical dependence on diazepam were examined in mice. Co-administration of flunarizine (T-type Ca2+ channel sensitive blocker), but not of either nifedipine or diltiazem (L-type Ca2+ channel sensitive blockers), with diazepam significantly suppressed the hypersensitivity to FG 7142 following chronic treatment with diazepam. The hypersensitivity to FG 7142 may reflect benzodiazepine withdrawal convulsions. These results suggest that flunarizine, but not nifedipine or diltiazem, may suppress the development of physical dependence on diazepam, and that T-type Ca2+ channels in the brain, rather than L-type Ca2+ channels, may be involved in the development of physical dependence on diazepam.

Animals↗

PubMed1993

Blockade of morphine reward through the activation of kappa-opioid receptors in mice.

The effects of systemic (s.c.) treatment with the kappa-agonists U-50,488H and E-2078 (a stable dynorphin analog) on the morphine-induced place preference were examined in mice. Morphine (s.c.) caused a dose-related preference for the drug-associated place; the effects at doses of 3 and 5 mg/kg were significant. On the other hand, U-50,488H or E-2078 produced a dose-related conditioned place aversion. Both U-50,488H (1 mg/kg, s.c.) and E-2078 (0.1 mg/kg, s.c.) induced a slight, nonsignificant place aversion. Pretreatment with U-50,488H (1 mg/kg) abolished the morphine (3 mg/kg)-induced place preference. The morphine-induced place preference was also significantly decreased by pretreatment with E-2078 (0.1 mg/kg). The inhibitory effects of the kappa-agonists were antagonized by the kappa-antagonist nor-binaltorphimine (nor-BNI; 3 mg/kg, s.c.). In contrast, pretreatment with U-50,488H did not affect the place preference induced by the dopamine (DA) receptor agonist apomorphine (1 mg/kg, s.c.). In addition, morphine (3 mg/kg, s.c.) significantly increased the levels of the DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the limbic forebrain (nucleus accumbens and olfactory tubercle) but not in the striatum, implying that activation of the mesolimbic DA system may play an important role in the morphine-induced place preference in mice. Pretreatment with U-50,488H significantly reduced the morphine-induced elevation of DA metabolites in the limbic forebrain.(ABSTRACT TRUNCATED AT 250 WORDS)

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

PubMed1993

Attenuation of anticonvulsant effects of diazepam after chronic treatment with bicuculline.

Changes in the GABAergic system after chronic treatment with bicuculline were examined in two strains of inbred rats, Fischer 344 (F344) and Lewis (LEW). Rats received an IP injection of either bicuculline (2 mg/kg) or vehicle once a day for 12 days. After this chronic treatment, the effects of diazepam (1 mg/kg, IP) and pentobarbital (20 mg/kg, IP) on bicuculline-induced convulsions were measured. Bicuculline was acutely infused into a tail vein at 0.0415 mg/min, and the infusion was terminated when rats showed seizure. Following the chronic bicuculline treatment, the anticonvulsant effect of diazepam, but not of pentobarbital, was significantly reduced as compared to its effect following chronic vehicle treatment in both strains. Both diazepam and pentobarbital showed a significant difference in anticonvulsant effects between strains (F344 > LEW). The hypnotic effects of muscimol, barbital, pentobarbital, and ethanol following chronic bicuculline treatment were examined. There was no significant difference in sleep time induced by these drugs between bicuculline- and vehicle-treated rats. These results suggest that the attenuation of diazepam's anticonvulsant effect after chronic bicuculline treatment may result from functional changes in benzodiazepine receptors and that the anticonvulsant effects of diazepam and pentobarbital may be influenced by genetic factors. Moreover, the hypnotic effects of several drugs tested are apparently not affected by chronic bicuculline treatment.

Animals↗

PubMed1993

Effects of flunarizine and diltiazem on physical dependence on barbital in rats.

The effects of flunarizine and diltiazem both on development of physical dependence on barbital and on barbital withdrawal signs in rats were examined using the drug-admixed food (DAF) method. Rats were chronically treated with barbital or barbital in combination with flunarizine (fixed at 1.5 mg/g of food) or diltiazem (fixed at 0.75 mg/g of food)-admixed food on the schedule of gradually increasing doses of barbital. Motor incoordination during the treatment was potentiated by coadministration of flunarizine, but not by coadministration of diltiazem. After the termination of drug treatment, the body weight loss and withdrawal scores were significantly suppressed in the group coadministered flunarizine, but not in that coadministered diltiazem. There were no significant differences in plasma barbital levels after the withdrawal between groups. In the substitution test, flunarizine (20 and 40 mg/kg, IP) significantly suppressed the body weight loss and withdrawal scores after the withdrawal, but diltiazem (20 mg/kg, IP) did not. These results indicated that flunarizine suppressed both the development of physical dependence on barbital and barbital withdrawal signs, mainly according to the suppression of convulsions, but not diltiazem, which is known to poorly penetrate into the brain. Therefore, the present findings suggest that central calcium channels may be involved in both the development of physical dependence on barbital and the appearance of barbital withdrawal signs.

Animals↗

PubMed1993

Strain differences in change in airway responsiveness after repeated antigenic challenge in three strains of rats.

1. The strain differences in 2,4-dinitrophenylated-Ascaris antigen-induced airway hyperresponsiveness (AHR) were investigated in three strains of rats: Brown-Norway (BN), Long-Evans Cinnamon (LEC) and Wistar. 2. Fourty-eight hour-passive cutaneous anaphylaxis titers after repeated challenge were highest in BN and lowest in LEC. 3. Twenty-four hours after the last challenge, a marked AHR and significant increase in wet/dry weight ratio of the main bronchus were observed only in Wistar. 4. Only the isolated bronchus of the challenged Wistar among the strains showed hyperresponsiveness to acetylcholine. 5. Wistar may be the best strain for antigen-induced AHR.

Acetylcholine↗

PubMed1993

Involvement of nitric oxide pathway in non-adrenergic non-cholinergic (NANC) relaxation in the rat stomach: differential innervation of NANC nerves in the longitudinal and circular muscle of the fundus.

1. The effects of NG-nitro-L-arginine (L-NNA) on non-adrenergic, non-cholinergic (NANC) relaxation elicited by transmural nerve stimulation (TNS) or high K+ were studied in the rat stomach fundus in order to investigate the mode of innervation of NANC nerves in the longitudinal and the circular muscle of the fundus. 2. Relaxation responses of the fundus to TNS were larger in circular than in longitudinal muscle strips. 3. Treatment with L-NNA (10(-5) M) reduced slightly but significantly the relaxation induced by TNS in both circular and longitudinal muscle strips of the fundus. The inhibitions of the TNS-induced relaxation by L-NNA were reversed partly by L-arginine (10(-3) M). 4. Although K+ produced concentration-dependent contraction in longitudinal muscle strips of the fundus, low concentration of K+ (20 mM) produced rapid and long-lasting relaxation in circular muscle strips of the fundus. 5. The 20 mM of K(+)-induced relaxation in circular muscle strips was significantly inhibited by L-NNA (10(-5) M) or oxyhemoglobin (2 x 10(-5) M). The inhibition of the K+ (20 mM)-induced relaxation by L-NNA was reversed by L-arginine (10(-3) M). 6. These results suggest that NO is one of mediators or transmitters in the NANC relaxation of the rat fundus, and that the density of NO-containing NANC nerves in the stomach fundus is richer in circular than in longitudinal muscle.

Animals↗

PubMed1993

Airway inflammatory effect of hydrogen peroxide in guinea pigs.

Reactive oxygens are now considered to be important substances in promoting inflammatory process. Recently, airway inflammation has attracted attention closely linked to bronchial asthma. The present study was undertaken to examine whether hydrogen peroxide, one of the reactive oxygens, could produce airway inflammation. Airway inflammation was assessed by airway vascular permeability in terms of pontamine sky blue (PSB) exudation. Airway resistance was measured with a modified Konzett-Rössler method and was expressed as a change in ventilation overflow. Inhalation of hydrogen peroxide (0.01-1.0 M) markedly caused a PSB exudation in a concentration-dependent manner in all of the trachea, main bronchus, and lungs. The hydrogen peroxide-induced PSB exudation effect was attenuated was attenuated by pretreatment with catalase, although heat-inactivated catalase had no inhibitory effect. Deferoxamine, which inhibits conversion of hydrogen peroxide into hydroxyl radical, decreased the PSB exudation induced by hydrogen peroxide. On the other hand, inhalation of hydrogen peroxide (1.0 M) caused a significant and biphasic increase in ventilation overflow. This airway constriction was suppressed by pretreatment with inhaled catalase, but not by inhaled deferoxamine. These results indicate that hydrogen peroxide causes an intense airway inflammation; this inflammatory effect may be mediated not only by hydrogen peroxide itself but also by hydroxyl radical. Hydrogen peroxide and hydroxyl radical may thus play an important role in bronchial asthma and bronchitis through inducing airway inflammation.

Administration, Inhalation↗

PubMed1993

Airway constriction by xanthine/xanthine oxidase in guinea pigs in vivo.

Reactive oxygens are considered to be one of the mediators involved in inflammation. We investigated the constrictive effects of reactive oxygens generated by aerosolized xanthine/xanthine oxidase (XOD) on the airways of anesthetized guinea pigs. Airway resistance was measured with a modified Konzett-Rössler method and expressed as a change in ventilation overflow (VO). Inhalation of xanthine (1.0 M)/XOD (10, 15 U/ml) caused a significant increase in VO. This airway constriction tended to be enhanced by pretreatment with inhaled superoxide dismutase, but was suppressed by inhaled catalase. Inhalation of hydrogen peroxide caused an airway constriction in a concentration-dependent manner (0.1-2.0 M). Xanthine/XOD significantly enhanced the maximal change in VO after inducing airway inflammation by SO2 exposure. The pretreatment with inhalation of xanthine/XOD did not affect the airway constriction induced by inhaled histamine. However, in SO2-exposed guinea pigs, the inhalation of xanthine/XOD significantly increased the sensitivity to histamine. These results indicate that hydrogen peroxide and other reactive oxygen intermediates produced by xanthine/XOD may cause an airway constriction and airway hyperresponsiveness.

Administration, Inhalation↗

PubMed1993

Repeated antigenic challenge-induced airway hyperresponsiveness and airway inflammation in actively sensitized rats.

Airway hyperresponsiveness (AHR) is a critical component in bronchial asthma, but the underlying mechanisms remain to be disclosed. Our present studies were performed to establish a new good experimental animal model of AHR. Male Wistar rats actively sensitized with DNP-Ascaris antigen (DNP-Asc) were challenged by inhaling DNP-Asc 8 days after the first immunization (single antigenic challenge). Another sensitization group received 3 challenges every 48 hr (repeated antigenic challenge). The airway responsiveness to inhalations of acetylcholine (ACh) and neurokinin A (NKA) were determined under anesthesia. The airway microvascular leakage was also determined with Evans blue (E.B.). At 24 hr after the single antigen challenge, the airway responsiveness to ACh and NKA were slightly enhanced, and the E.B. exudation was increased in the main bronchus. In contrast, the airway responsiveness to ACh and NKA and the E.B. exudation in the main bronchus were much more markedly enhanced 24 hr after the repeated antigenic challenge. The isolated main bronchial strip from the challenged rats had obtained AHR towards ACh and serotonin. These findings suggest that repeated antigenic challenge causes a distinct AHR, both in vivo and in vitro, and that the airway inflammation may be closely related to pathogenesis of AHR.

Acetylcholine↗

PubMed1993

Effects of kappa-agonist on the antinociception and locomotor enhancing action induced by morphine in mice.

The antinociception of intracerebroventricular injection (i.c.v.) of morphine was markedly abolished by pretreatment with naloxonazine (micro 1-antagonist), s.c.; beta-funaltrexamine (micro 1/micro 2-antagonist), i.c.v.; DSP-4 (noradrenaline neurotoxin), s.c.; or p-chlorophenylalanine (serotonin synthesis inhibitor), s.c. in the mouse 55 degrees C hot-plate assay. Pretreatment with nor-binaltorphimine (kappa-antagonist), i.c.v. or PCPA, s.c. drastically blocked the kappa-agonist U-50,488H-induced supraspinal antinociception. These findings indicate either noradrenergic or serotonergic involvement in the mediation of the antinociceptio of i.c.v.-morphine through mu-receptors. On the contrary, the antinociception of i.c.v.- U-50,488H through kappa-receptors appears to depend on the serotonergic but not noradrenergic systems. The antinociceptive interaction between the i.c.v.-morphine and -U-50,488H was an additive effect. On the other hand, i.c.v.-morphine dose-dependently increased the locomotion in mice, and this hyperlocomotion of morphine was drastically blocked by pretreatment with either beta-funaltrexamine, i.c.v. or 6-hydroxydopamine (dopamine depletor), i.c.v. I.c.v.-U-50,488H dose-dependently reduced the increasing locomotion of i.c.v.-morphine, but not that of s.c.-apomorphine (dopamine receptor agonist), and this effect of U-50,488H was completely reversed by pretreatment with nor-binaltorphimine, i.c.v. These results suggest that coadministration of kappa-agonists can suppress the dopamine-related hyperlocomotion of mu-agonists without decreasing the anti-nociception of mu-agonists in mice.

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

PubMed1993

Effects of mast cell growth factor, interleukin-3, and interleukin-6 on human primitive hematopoietic progenitors from bone marrow and cord blood.

Phycoerythrin (PE)-labeled murine monoclonal antibodies (MAB) to CD2, CD10, CD19, CD20, and CD33 were used as lineage markers, as were PE-labeled anti-DR MAB and fluorescein isothiocyanate (FITC)-conjugated MAB to CD34. One hundred CD34+Lin+DR+ or CD34+Lin-DR- cells were individually sorted and incubated without adherent cell layer in alpha-medium with or without cytokines such as 100 U/mL recombinant human interleukin-3 (rhIL-3), 100 U/mL rhIL-6, and/or 500 ng/mL mast cell growth factor (MGF). The incubated cells were harvested and cultured in medium containing methylcellulose every 2 weeks. The numbers of colonies from colony-forming units-granulocyte/macrophage (CFU-GM), burst-forming units-erythroid (BFU-E), and mixed colony-forming units (CFU-Mix) were scored on day 14. In the incubation, CD34+Lin-DR- cells from bone marrow and cord blood produced more CFU-GM and BFU-E, and for longer periods, than did CD34+Lin+DR+ cells. In addition, CD34+Lin-DR- from cord blood supplied more CFU-GM and BFU-E than did CD34+Lin-DR- from bone marrow. Although these data demonstrate that MGF, IL-3, and IL-6 synergistically stimulate the production of CFU-GM and BFU-E, this study indicates that CD34+Lin-DR- cells contain more primitive hematopoietic progenitors and that CD34+Lin-DR- cells are unable to maintain their self-renewal capacity in the presence of IL-3, IL-6, and MGF without adherent cell layer.

Adult↗

PubMed1993

Antitussive effect of captopril, an angiotensin converting enzyme inhibitor, in the rat.

The effects of acute treatment with captopril, an angiotensin converting enzyme inhibitor, on the capsaicin-induced cough reflex were examined in rats. Intraperitoneal injection of captopril in doses of 3 and 10 mg/kg decreased the number of coughs dose-dependently. Although the peak effect was similar to that of morphine (0.5 mg/kg), the duration of captopril's effect (10 mg/kg) was longer than that of morphine. Furthermore, while pretreatment with naloxone significantly decreased the duration of the antitussive effect of captopril, it had no significant effect on the early-phase (within 60 min) effect of captopril. These results suggest that the mechanism which underlies the antitussive effect of captopril involves mediation by both nonopioid and opioid systems.

Animals↗