Biomedical subjects

M Misawa

Publications and source records attributed to M Misawa.

At least 127 records · Page 7Linked to original sources

PubMed1994

Antigen-induced airway hyperresponsiveness is associated with airway tissue NEP hypoactivity in rats.

In the present study, the role of sensory neuropeptides in the airway hyperresponsiveness (AHR) was investigated. First, the effect of the depletion of sensory neuropeptides by systemic capsaicin treatment on the AHR to acetylcholine (ACh) induced by repeated antigenic challenge to sensitized rats was studied. We secondly investigated whether the neutral endopeptidase (NEP) activity was altered at the antigen-induced AHR. Male Wistar rats were sensitized and repeatedly challenged with DNP-Ascaris antigen. Twenty-four hours after the last antigenic challenge, a marked AHR to inhaled ACh (0.001-0.03%) was observed. This AHR was significantly attenuated by systemic capsaicin pretreatment prior to sensitization. On the other hand, in normal rats, the airway responsiveness to inhaled ACh was significantly increased by pretreatment with NEP inhibitor, phosphoramidon (3 mg/kg, i.v.), but the NEP inhibitor-induced effect was no more observed in the antigen-induced AHR rats. Furthermore, it was found that the airway NEP activity was significantly decreased at the antigen-induced AHR. These findings suggest that NEP hypoactivity and resultant increased sensory neuropeptides have an important role in the pathogenesis of antigen-induced AHR in rats.

Acetylcholine↗

PubMed1994

The differential effects of histamine receptor antagonists on morphine- and U-50,488H-induced antinociception in the mouse.

The effects of thioperamide, an H3 antagonist, and histamine H1 and H2 antagonists (s.c.) on morphine (s.c. or i.c.v.)- and U-50,488H (i.c.v.)-induced antinociception in male ddY mice were examined using the hot-plate (55 degrees C) test. Thioperamide significantly inhibited morphine-induced antinociception, but not U-50,488H-induced antinociception. The suppressive effect of thioperamide on morphine-induced antinociception was reversed by the H1 antagonist pyrilamine, but not by the H2 antagonist zolantidine. On the other hand, pyrilamine significantly potentiated the antinociception induced by morphine, but not that induced by U-50,488H. Zolantidine significantly inhibited morphine-induced antinociception in a dose-dependent manner, but not U-50,488H-induced antinociception. Both astemizole, an H1 antagonist, and ranitidine, an H2 antagonist, which are known to barely cross the blood brain barrier, did not affect morphine-induced antinociception. These results suggest that morphine-induced antinociception may be potentiated by activation of H2 receptors and suppressed by activation of H1 receptors in the brain. Furthermore, neuronal histamine release induced by thioperamide may suppress morphine-induced antinociception through H1 receptors.

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

PubMed1994

Effects of a lipopolysaccharide from Pantoea agglomerans on the cocaine-induced place preference.

A lipopolysaccharide from Pantoea agglomerans (LPSp) was purified, and its effect on the cocaine-induced place preference was examined in rats. Cocaine (4 mg/kg, i.p.) produced a significant place preference. Administration of LPSp (5-1000 micrograms/kg, i.p.) alone resulted in neither preference nor aversion for either the drug- or saline-associated place. However, pretreatment with LPSp (500 and 1000 micrograms/kg, i.p.) abolished the place preference that had been induced by cocaine. Furthermore, treatment with LPSp (500 micrograms/kg, i.p.) abolished cocaine (20 mg/kg, i.p.)-induced locomotor enhancement in mice. These results suggest that while LPSp itself may possess neither reinforcing nor locomotor enhancing effects, it blocks both the reinforcing and the locomotor enhancing effects of cocaine. Therefore, LPSp might be useful in pharmacotherapy for prevention of recurrent cocaine abuse.

Animals↗

PubMed1994

The role of delta-opioid receptor subtypes in cocaine- and methamphetamine-induced place preferences.

The effects of delta-receptor antagonists on cocaine- and methamphetamine-induced place preferences were examined in rats. Cocaine- and methamphetamine-induced place preferences were significantly attenuated by naltrindole (NTI: a non-selective delta-opioid receptor antagonist). Furthermore, naltriben (NTB: a selective delta 2-opioid receptor antagonist), but not 7-benzylidenenaltrexone (BNTX: a selective delta 1-opioid receptor antagonist), attenuated the cocaine- and methamphetamine-induced place preferences. These results suggest that delta-opioid receptors, particularly delta 2-opioid receptors, may be involved in the reinforcing effects of cocaine and methamphetamine.

Animals↗

PubMed1994

Potentiation of physical dependence on diazepam by ondansetron in rats.

The effects of ondansetron, a 5-HT3 antagonist, on the development of physical dependence on diazepam were examined in rats using a drug-admixed food method. Rats were treated with diazepam or diazepam in combination with ondansetron for 26 days. After an abrupt withdrawal from diazepam, the incidence of withdrawal signs, such as jerks, tremors and convulsions, and withdrawal scores, were potentiated by co-administration of ondansetron. On the other hand, rats which had been treated with ondansetron alone for 33 days did not show any withdrawal signs after abrupt withdrawal from ondansetron. These findings suggest that ondansetron does not possess physical dependence liability, but does potentiate the development of physical dependence on diazepam. Regulation of serotonergic neurons through 5-HT3 receptors may affect the development of physical dependence on diazepam.

Animals↗

PubMed1994

Role of beta-adrenoceptors in the expression of morphine withdrawal signs.

The effects of intracerebroventricular (i.c.v.) pretreatment with the noradrenergic neurotoxin DSP-4 and beta 1- and beta 2-adrenoceptor antagonists on the expression of morphine withdrawal signs were investigated in mice. Mice were chronically treated with morphine (8-45 mg/kg, s.c.). Several withdrawal signs were observed following naloxone challenge in morphine-dependent mice which had been pretreated with vehicle. Treatment with DSP-4 before the naloxone challenge suppressed the expression of morphine withdrawal signs, including jumping and "wet dog" shakes. Similarly, pretreatment with the beta 1-antagonist atenolol significantly reduced the incidence of naloxone-precipitated jumping and "wet dog" shakes. However, pretreatment with the beta 2-antagonist ICI118,551 suppressed the expression of "wet dog" shakes, but not that of jumping. These findings suggest that the central noradrenergic system may mediate the expression of withdrawal signs. The blocking effects of beta-antagonists indicate that naloxone-precipitated jumping may be mediated predominantly by beta 1-adrenoceptors, while naloxone-precipitated "wet dog" shakes may be mediated by both beta 1- and beta 2-adrenoceptors.

Adrenergic Agents↗

PubMed1994

Streptozotocin-induced diabetes selectively enhances antinociception mediated by delta 1- but not delta 2-opioid receptors.

We assessed the effect of diabetes on antinociception produced by intracerebroventricular injection of delta-opioid receptor agonists [D-Pen2,5]enkephalin (DPDPE) and [D-Ala2]deltorphin II. The antinociceptive effect of DPDPE (10 nmol), administered i.c.v., was significantly greater in diabetic mice than in non-diabetic mice. The antinociceptive effect of i.c.v. DPDPE was significantly reduced in both diabetic and non-diabetic mice following pretreatment with 7-benzylidenenaltrexone (BNTX), a selective delta 1-opioid receptor antagonist, but not with naltriben (NTB), a selective delta 2-opioid receptor antagonist. There were no significant differences in the antinociceptive effect of [D-Ala2]deltorphin II (3 nmol, i.c.v.) in diabetic and non-diabetic mice. Furthermore, the antinociceptive effect of i.c.v. [D-Ala2]deltorphin II was significantly reduced in both diabetic and non-diabetic mice following pretreatment with NTB, but not with BNTX. In conclusion, mice with diabetes are selectively hyper-responsive to supraspinal delta 1-opioid receptor-mediated antinociception, but are normally responsive to activation of delta 2-opioid receptors.

Analgesia↗

PubMed1994

Differential mediation of cold water swim stress-induced antinociception by delta-opioid receptor subtypes in diabetic mice.

The involvement of delta-opioid receptor subtypes in cold water swim stress (CWSS)-induced antinociception in diabetic mice was compared with that in non-diabetic mice. Three-minute swim stress produced significant antinociception in both diabetic and non-diabetic mice as determined by the tail-pinch test. However, the extent of CWSS-induced antinociception in diabetic mice was significantly greater than that in non-diabetic mice. Pretreatment with naltriben, a selective delta 2-opioid receptor antagonist, significantly attenuated CWSS-induced antinociception in both non-diabetic and diabetic mice. In contrast, although 7-benzylidenenaltrexone, a selective delta 1-opioid receptor antagonist, significantly attenuated CWSS-induced antinociception in diabetic mice, it had no effect in non-diabetic mice. These results suggest that CWSS-induced antinociception in non-diabetic mice is mediated by delta 2-opioid receptors, whereas CWSS-induced antinociception in diabetic mice is mediated by both delta 1- and delta 2-opioid receptors. Furthermore, the enhanced CWSS-induced antinociception in diabetic mice may be due to the activation of delta 1-opioid receptors.

Analgesia↗

PubMed1994

Evidence for differential modulation of mu-opioid receptor-mediated antinociceptive and antitussive activities by spleen-derived factor(s) from diabetic mice.

The effects of spleen-derived factor(s) from diabetic mice on the antinociceptive and antitussive effects of mu-opioid receptor agonists were examined in mice. The antinociceptive effects were examined 1 week after adoptive transfer of the supernatant of spleen cell homogenate (SSCH) from diabetic mice (SSCH-D). Naive mice which had been injected with SSCH-D were less sensitive to the antinociceptive effects of mu-opioid receptor agonists, such as morphine and [D-Ala2, N-MePhe4, Gly-ol5]enkephalin (DAMGO), than mice which had been injected with SSCH from non-diabetic mice. The antinociceptive effects of DAMGO was also significantly lower in naive mice injected with SSCH-D than in SSCH from non-diabetic mice (SSCH-ND)-treated naive mice, when assessed 2 weeks after adoptive transfer of SSCH. The sensitivity to the antinociceptive effect of [D-Pen2,5]enkephalin (DPDPE), a delta-opioid receptor agonist, was significantly enhanced 2 weeks, but not 1 week, after adoptive transfer of SSCH-D. On the other hand, adoptive transfer of SSCH-D to naive mice had no significant effect on the recipients' antitussive sensitivities to morphine and DAMGO when assessed 1 week after transfer of SSCH-D. However, when the antitussive effect was assessed 2 weeks after adoptive transfer of SSCH, the antitussive effect of DAMGO was significantly lower in naive mice injected with SSCH-D than in SSCH-ND-treated naive mice. The reduction in the antitussive effect of DAMGO in naive mice had been injected with SSCH-D 2 weeks before testing was abolished when they were pretreated with naltrindole, a selective delta-opioid receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗

PubMed1994

Suppression of hyperalgesia in streptozotocin-induced diabetic mice by a lipopolysaccharide from Pantoea agglomerans.

The ability of a lipopolysaccharide from Pantoea agglomerans (LPSp) to relieve hyperalgesia was examined by observing its inhibition of the decrease in the threshold for nociceptive perception, as determined by the tail-pinch test, in streptozotocin-induced diabetic mice. Subcutaneous injection of LPSp suppressed hyperalgesia in streptozotocin-induced diabetic mice and also exerted a therapeutic effect on hyperalgesia in these animals. The present data suggest that LPSp may be effective in relieving the pain associated with diabetic neuropathy.

Animals↗

PubMed1994

Blockade of delta-opioid receptors prevents morphine-induced place preference in mice.

Effects of highly selective delta-opioid receptor antagonists on the morphine-induced place preference in ddY and mu 1-opioid receptor deficient CXBK mice were investigated. Pretreatment with naltrindole (NTI: a non-selective delta-opioid receptor antagonist), 7-benzylidenenaltrexone (BNTX: a selective delta 1-opioid receptor antagonist) or naltriben (NTB: a selective delta 2-opioid receptor antagonist) abolished the morphine-induced place preference in ddY mice in a dose-dependent manner. These findings suggest that the morphine-induced place preference may be mediated by both delta 1- and delta 2-opioid receptors. On the other hand, in mu 1-opioid receptor deficient CXBK mice, pretreatment with these selective delta-opioid receptor antagonists did not affect the morphine-induced place preference, although pretreatment with beta-funaltrexamine (beta-FNA: a selective mu-opioid receptor antagonist) significantly inhibited the morphine-induced place preference. [D-Pen2,D-Pen5]enkephalin (DPDPE: a delta 1-opioid receptor agonist) and [D-Ala2,Glu4]deltorphin (deltorphin II: a delta 2-opioid receptor agonist) induced a significant place preference in ddY mice, but not in CXBK mice. These results suggest that delta 1- and delta 2-opioid receptors in the nucleus accumbens that are related to the DPDPE- and deltorphin II-induced place preference may be dysfunctional and/or poor in CXBK mice. These findings also indicate that delta 1- and delta 2-opioid receptors may be involved in the modulation of the reinforcing effect of morphine.

Analgesics↗

PubMed1994

[The proposal for community pharmacist activity from a viewpoint of science history].

Community pharmacists have many kinds of problems for demonstrating their ability and activity. One of them is to realize the professional activity. At present, I am afraid that such community professional activities might be for now confined to legal extension. I would therefore like to discuss the aspect of professional centrifugal practice in community health care system under the pharmaceutical law system. Secondly, the role of pharmacists in drug sale comprises advising and controlling medication that we call "Application Pharmacy" in which individual pharmacokinetics and susceptivities have to be considered. The Application Pharmacy will be established in the community medical health care system for new pharmacist's activity. The Application Pharmacy should be a requirement for community pharmacists and lead to a notion of "Community Pharmacy Therapeutics."].

Community Pharmacy Services↗

PubMed1994

Inhibition of antigen-induced airway hyperresponsiveness in rats: effects of ozagrel (a thromboxane A2 synthase inhibitor) and of CV-3988 (a platelet activating factor antagonist).

The effects of ozagrel, a thromboxane A2 (TXA2) synthase inhibitor, and CV-3988, a platelet activating factor (PAF) antagonist, was investigated on the repeatedly antigenic challenge-induced airway hyperresponsiveness (AHR) in rats. Rats were actively sensitized with DNP-Ascaris antigen and received 3 inhalations of antigen (challenges) or saline (sensitized control) every 48 hr. These animals were also pretreated with ozagrel (100 mg/kg, p.o., 30 min before), CV-3988 (3 mg/kg, i.v., 5 min before) or respective vehicle (water and saline, respectively) before each inhalation of antigen or saline. The in vivo airway responsiveness to cumulatively inhaled acetylcholine (ACh; 0.001-0.03%, each for 3 min) was measured 24 hr after the last inhalation of antigen or saline under anesthesia. A marked AHR was observed after repeated antigenic challenge when compared with the sensitized control group (5.5-9.5 times in order). This AHR was significantly, but partly, attenuated by pretreatment with ozagrel although this treatment alone had no effect on the airway responsiveness to inhaled ACh in sensitized control animals. On the other hand, CV-3988 had no inhibitory effect on this AHR. These findings suggest that TXA2, but not PAF, is one of the most important mediators participating in the pathogenesis of the antigen-induced AHR in rats.

Acetylcholine↗

PubMed1994

Antitussive effect of (+/-) pentazocine in diabetic mice is mediated by delta-sites, but not by mu- or kappa-opioid receptors.

The effects of streptozotocin-induced diabetes on the antitussive effect of (+/-) pentazocine were examined in mice. Intracerebroventricular (i.c.v.) administration of (+/-) pentazocine produced a dose-dependent antitussive effect in both diabetic and non-diabetic mice. There were no significant differences in the antitussive effect of (+/-) pentazocine in diabetic and non-diabetic mice. The antitussive effect of i.c.v. (+/-) pentazocine was partially, but significantly, reduced in non-diabetic mice following pretreatment with either beta-funaltrexamine, a selective mu-opioid antagonist, or rimcazole, a specific sigma-site antagonist. The antitussive effect of (+/-) pentazocine in diabetic mice was significantly antagonized by pretreatment with rimcazole. However, beta-funaltrexamine had no effect on the antitussive effect of (+/-) pentazocine in diabetic mice. Furthermore, nor-binaltorphimine, a selective kappa-opioid receptor antagonist, had no significant effect on the antitussive effect of (+/-) pentazocine in either non-diabetic or diabetic mice. These results suggest that although the antitussive effect of i.c.v. (+/-) pentazocine in non-diabetic mice is mediated by both mu-opioid receptors and sigma-sites, in diabetic mice this effect is mainly mediated by sigma-sites.

Animals↗

PubMed1994

Cough-induced activity of (-)-(2S, 3aR, 7aS)-1-[(S)-N-[(S)-1-ethoxycarbonyl-3- phenylpropyl]alanyl]hexahydro-2-indolinecarboxylic acid (trandolapril) in guinea pigs.

We examined the effect of trandolapril ((-)-(2S, 3aR, 7aS)-1-[(S)-N-[(S)-1-ethoxycarbonyl-3- phenylpropyl]alanyl]hexahydro-2-indolinecarboxylic acid), a potent angiotensin converting enzyme (ACE) inhibitor, on the number of capsaicin-induced coughs in guinea pigs and compared it with that of enalapril. Chronic treatment with enalapril, at a dose of 3 mg/kg, p.o., significantly enhanced the number of capsaicin-induced coughs. Chronic treatment with trandolapril, at doses of 1 and 3 mg/kg, p.o., slightly enhanced the number of capsaicin-induced coughs. However, there were no significant differences in the number of capsaicin-induced coughs between trandolapril-treated and vehicle-treated animals. These results suggest that cough induced activity, one of the most serious side effects associated with chronic treatment with ACE inhibitors, of trandolapril is relatively lower than that of enalapril.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1994

Effects of diabetes on the antinociceptive effect of (+/-)pentazocine in mice.

The antinociceptive effect of (+/-)pentazocine was examined in streptozotocin-induced diabetic mice. Although intracerebroventricular (i.c.v.) administration of (+/-)pentazocine (10 nmol) produced a significant antinociceptive effect in both non-diabetic and diabetic mice, the antinociceptive effect of (+/-)pentazocine was greater in diabetic mice than in non-diabetic mice. The antinociceptive effects of (+/-)pentazocine in both diabetic and non-diabetic mice were significantly antagonized by s.c. administration of nor-binaltorphimine, a selective kappa-opioid receptor antagonist. On the other hand, the antinociceptive effects of (+/-)pentazocine were potentiated when non-diabetic mice were pretreated with beta-funaltrexamine, a selective mu-opioid receptor antagonist. Furthermore, there was no significant difference in the antinociceptive effect of (+/-)pentazocine between diabetic mice and beta-funaltrexamine-treated non-diabetic mice. These results suggest that the hypo-responsiveness of mu-opioid receptors may account for the enhanced kappa-opioid receptor-mediated antinociceptive effect of (+/-)pentazocine in diabetic mice.

Analgesics↗

PubMed1993

Antitussive effects of naltrindole, a selective delta-opioid receptor antagonist, in mice and rats.

The effects of naltrindole, a selective delta-opioid receptor antagonist, on the capsaicin-induced cough reflex in mice and rats were studied. Intraperitoneal administration of naltrindole decreased the number of coughs both in mice and rats dose dependently. The cough-depressant effects reached a peak 15 min after the administration of naltrindole and lasted more than 120 min. Pretreatment with [D-Pen2,D-Pen5]enkephalin, a selective delta-opioid receptor agonist, partially but significantly reduced the antitussive effect of naltrindole. Blockade of kappa-opioid receptors by pretreatment with nor-binaltorphimine also partially antagonized the antitussive effect of naltrindole. However, the antitussive effect of naltrindole was not antagonized by beta-funaltrexamine, a selective mu-opioid receptor antagonist. Thus, it is possible that the antitussive effect of naltrindole may be mediated, in part, by kappa-opioid receptors. The present results provide evidence for the development of delta-opioid antagonists, especially naltrindole, for use as antitussive drugs.

Animals↗

PubMed1993

Effect of cyclosporine A on the morphine-induced place preference.

The effect of pretreatment with cyclosporine A, an immunosuppressant, on the morphine-induced place preference was examined in ddY and mu1 opioid receptor-deficient CXBK mice. Morphine produced a significant preference for the drug-associated place in ddY and CXBK mice. Administration of cyclosporine A alone to ddY and CXBK mice did not result in either preference or aversion for either the drug- or vehicle-associated place. On the other hand, pretreatment with cyclosporine A suppressed the place preference induced by morphine in ddY mice in a dose-dependent manner. However, in CXBK mice, pretreatment with cyclosporine A did not affect the morphine-induced place preference. These results suggest that cyclosporine A suppresses the reinforcing effect induced by morphine, and that this suppression by cyclosporine A may be mediated by mu1 opioid receptors.

Animals↗