Biomedical subjects

M Misawa

Publications and source records attributed to M Misawa.

At least 91 records · Page 5Linked to original sources

PubMed1996

Beta 2- but not beta 1-adrenoceptors mediate the adrenergic component of reflex tracheal dilatation during bronchoconstriction in guinea pigs in vivo.

Involvement of beta 1- and/or beta 2-adrenoceptors in vagal reflex-mediated tracheal dilatation during bronchoconstriction was investigated using the in vivo guinea pig tracheo-bronchi separated preparation. Inhalation of 0.01% (w/v) histamine to the bronchial site produced vagal reflex-mediated tracheal constriction followed by dilatation slightly after bronchial constriction. The latter reflex dilatation was significantly inhibited not only by 1% propranolol, a nonselective beta-adrenoceptor antagonist, but also by 0.1% butoxamine and 0.01% ICI-118,551, selective beta 2-adrenoceptor antagonists. However, 0.1% atenolol, a selective beta 1-adrenoceptor antagonist failed to inhibit the dilatation. Furthermore, the dilatation was also inhibited by 0.1% guanethidine treatment or adrenalectomy. All of noradrenaline, adrenaline and cyclic AMP contents in the tissue of the tracheal site significantly increased during the reflex tracheal dilatation after bronchoconstriction. The increase in cyclic AMP was reduced by 1% propranolol. Furthermore, local treatment of the tracheal site with 0.01% noradrenaline or 0.01% adrenaline induced tracheal dilatation, which was significantly inhibited by 0.1% butoxamine or 0.001% ICI-118,551 but not by 0.1% atenolol. These results suggest that the reflex tracheal dilatation during bronchoconstriction may be mediated by mainly beta 2-adrenoceptors activated by adrenaline released from the adrenal medulla and by noradrenaline released from the adrenergic nerve terminals.

Administration, Inhalation↗

PubMed1995

Discriminative stimulus properties of morphine mediated by mu 1-opioid receptors.

The mu-opioid receptor subtypes involved in the discriminative stimulus properties of morphine were investigated in rats that had been trained to discriminate between 3.0 mg/kg morphine and saline. The discriminative stimulus properties of morphine were significantly attenuated by beta-funaltrexamine (an irreversible mu-opioid receptor antagonist: 10 and 20 mg/kg) and naloxonazine (an irreversible mu 1-opioid receptor antagonist: 20 mg/kg). These results suggest that the discriminative stimulus properties of morphine may be mediated by mu 1-opioid receptors.

Analgesics, Opioid↗

PubMed1995

Blockade of morphine-induced place preference by diazepam in mice.

The effects of diazepam on morphine-induced place preference were examined in mice. Pretreatment with diazepam (2 mg/kg i.p.) 30 min prior to morphine injection significantly abolished the morphine (5 mg/kg s.c.)-induced place preference, and this effect of diazepam was antagonized by pretreatment with flumazenil. In addition, pretreatment with diazepam prevented the morphine (5 mg/kg s.c.)-induced increase in dopamine turnover in the limbic forebrain. These results suggest that pretreatment with diazepam may suppress the rewarding effects of morphine.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1995

Alteration in Ca2+ availability involved in antigen-induced airway hyperresponsiveness in rats.

The origin of Ca2+ contributing to the enhancement of acetylcholine-induced bronchial smooth muscle constriction in airway hyperresponsiveness induced by antigen challenge was investigated. Under Ca(2+)-free (concomitant with 10(-6) M nicardipine) conditions, the contractile responses of bronchial rings to 1 mM acetylcholine were significantly greater in rings from rats with hyperresponsive airways (0.15 +/- 0.04 g) than those of rings from normal rats (0.02 +/- 0.004 g; P < 0.05). The cumulatively administered Ca2+ induced a markedly greater bronchoconstriction in rings from rats with hyperresponsive airways in Ca(2+)-free solution when muscles were pretreated with 1 mM acetylcholine (in the presence of 10(-6) M nicardipine) than in rings from normal rats, whereas no significant difference in Ca(2+)-induced bronchoconstriction was observed between the two groups when muscles were pretreated with 60 mM K+ (in the presence of 10(-6) M atropine). These findings suggest that enhancement of the availability of Ca2+ released from intracellular stores and/or influxed through receptor-operated Ca2+ channels in airway smooth muscles might be involved in the airway hyperresponsiveness to acetylcholine in rats.

Acetylcholine↗

PubMed1995

Effects of the histaminergic system on the morphine-induced conditioned place preference in mice.

The effects of an H2 receptor antagonist, a histidine decarboxylase inhibitor and a histamine precursor on the morphine-induced place preference in mice were examined. Morphine (1-7 mg/kg) produced a place preference in a dose-dependent manner. This morphine-induced place preference was significantly antagonized by the dopamine (DA) D1 receptor antagonist SCH 23390. The histamine precursor, L-histidine, attenuated the morphine (7 mg/kg)-induced place preference. On the other hand, the histidine decarboxylase inhibitor, alpha-fluoromethylhistidine (alpha-FMH), significantly potentiated the morphine (1 mg/kg)-induced place preference. This potentiation was antagonized by SCH 23390. The H2 receptor antagonist zolantidine (0.3 mg/kg) significantly potentiated the morphine-induced place preference. Surprisingly, zolantidine (1 mg/kg) alone also produced a significant place preference. The zolantidine-induced place preference was antagonized by SCH 23390. In addition, zolantidine (1, 3 and 10 mg/kg) significantly increased DA turnover (DA ratio) in the limbic forebrain (nucleus accumbens and olfactory tubercle), implying that zolantidine may activate the mesolimbic DA system. Moreover, co-administration of zolantidine dose-dependently increased morphine (10 mg/kg)-induced DA turnover in the limbic forebrain. These results suggest that the activation of histaminergic neurons may attenuate the rewarding effect of morphine, while the inhibition of histaminergic neurons may potentiate the rewarding effect of morphine. Furthermore, potentiation of the morphine-induced rewarding effect by inhibition of histaminergic neurons may be mediated by D1 receptors. We also demonstrated that the H2 receptor antagonist zolantidine may activate the mesolimbic DA system, and as a result, zolantidine itself produces a rewarding effect and potentiates the morphine-induced rewarding effect.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1995

Antinociceptive effects of the selective non-peptidic delta-opioid receptor agonist TAN-67 in diabetic mice.

The antinociceptive potencies of 2-methyl-4 alpha alpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12 alpha alpha-octahydro-quinolino[2,3,3-g]isoquinoline (TAN-67), a non-peptidic delta-opioid receptor agonist, were examined using the acetic acid abdominal constriction test and the tail-flick test in diabetic mice. TAN-67, at doses of 3-100 mg/kg, s.c. [corrected], produced a marked and dose-dependent inhibition of the number of acetic acid-induced abdominal constrictions in both non-diabetic and diabetic mice. The antinociceptive effect of TAN-67 in the acetic acid abdominal constriction test in diabetic mice was greater than that in non-diabetic mice. Indeed, the ED50 (95% confidence limits) value of TAN-67 for the inhibition of acetic acid-induced abdominal constrictions in diabetic mice (6.0 (3.5-10.5) mg/kg) was significantly lower than that in non-diabetic mice (31.4 (14.2-69.4) mg/kg). The antinociceptive effect of TAN-67 was not antagonized by pretreatment with either beta-funaltrexamine, a selective mu-opioid receptor antagonist, or nor-binaltorphimine, a selective kappa-opioid receptor antagonist. When 7-benzylidenenaltrexone (0.3 mg/kg, s.c.), a selective delta 1-opioid receptor antagonist, was administered 10 min before treatment with TAN-67, the antinociceptive effect of TAN-67 was significantly antagonized. However, naltriben, a selective delta 2-opioid receptor antagonist, had no significant effect on the antinociceptive effect of TAN-67. Furthermore, in the tail-flick test, TAN-67 at doses of 3-30 mg/kg, s.c. [corrected], also produced a marked and dose-dependent antinociceptive effect in diabetic mice, but not in non-diabetic mice. In conclusion, TAN-67 produced an antinociceptive effect through the activation of delta 1-opioid receptors. Furthermore, the results of this study support our hypothesis that mice with diabetes are selectively hyperresponsive to delta 1-opioid receptor-mediated antinociception.

Analgesics↗

PubMed1995

Adrenalectomy potentiates the morphine--but not cocaine-induced place preference in rats.

The conditioned place preference paradigm is commonly used to study the reinforcing properties of various drugs. In the present study, the effect of adrenalectomy (ADX) on the morphine-induced place preference was examined in rats. Morphine produced a significant preference for the drug-associated place in sham-operated (sham) and ADX rats. In sham rats, only the highest dose of morphine (8 mg/kg, i.p.) produced a significant preference, while in ADX rats, lower doses of morphine (1 and 2 mg/kg, i.p.) produced a significant preference for the drug-associated place. Furthermore, the morphine-induced place preference was blocked by the dopamine D1 antagonist SCH23390 in both sham and ADX rats. On the other hand, the cocaine-induced place preference was not affected by ADX. In the present study, we found that ADX potentiates the reinforcing effect induced by morphine, but not that induced by cocaine, which suggests that the enhancement by ADX may be due to a change in opioid receptors, morphine metabolism and/or some other cause, but not a change in dopamine receptors.

Adrenalectomy↗

PubMed1995

Buprenorphine exerts its antinociceptive activity via mu 1-opioid receptors.

The mechanism of the antinociceptive effect of buprenorphine was assessed by administering selective mu-, mu1--, delta- and kappa-opioid receptor antagonists in mice. Intraperitoneal administration of buprenorphine, at doses of 0.3 to 3 mg/kg, produced dose-dependent antinociception in the tail-flick test. The antinociceptive activity of buprenorphine did not result from the activation of kappa- or delta-opioid receptors, since treatment with either nor-binaltorphimine, a selective kappa-opioid receptor antagonist, or naltrindole, a selective delta-opioid receptor antagonist, was completely ineffective in blocking buprenorphine-induced antinociception. However, the antinociceptive effect of buprenorphine was significantly antagonized by beta-funaltrexamine, a selective mu-opioid receptor antagonist. Moreover, selective mu1-opioid receptor antagonist, naloxonazine and naltrexonazine, also significantly antagonized the antinociceptive effect of buprenorphine. Co-administration of kappa- and delta-opioid receptor antagonist with the mu-opioid receptor antagonists had no significant effect on the antagonistic profiles of the mu-opioid receptor antagonists on the antinociceptive effect of buprenorphine. These results suggest that buprenorphine acts selectively at mu1-opioid receptors to induce antinociceptive effects in mice.

Analgesics, Opioid↗

PubMed1995

Antinociceptive effect of dihydroetorphine in diabetic mice.

The antinociceptive potency of dihydroetorphine in diabetic mice was examined. Subcutaneous administration of dihydroetorphine produced a dose-dependent antinociception in both non-diabetic and diabetic mice. The antinociceptive potency of s.c. dihydroetorphine was less in diabetic mice than in non-diabetic mice. The antinociception induced by i.c.v. dihydroetorphine (0.02 microgram) was also significantly less in diabetic mice than in non-diabetic mice. The antinociceptive effects of dihydroetorphine (10 micrograms/kg i.p.) in both diabetic and non-diabetic mice were significantly antagonized by s.c. administration of beta-funaltrexamine, a selective mu-opioid receptor antagonist. Furthermore, the antinociceptive effect of dihydroetorphine (10 micrograms/kg i.p.) in non-diabetic mice, but not in diabetic mice, was also significantly antagonized by naloxonazine, a selective mu 1-opioid receptor antagonist. The time course and the potency of the antinociceptive effect of dihydroetorphine (10 micrograms/kg i.p.) in diabetic mice were similar to those in naloxonazine-treated non-diabetic mice. Naltrindole, a selective delta-opioid receptor antagonist, or nor-binaltorphimine, a selective kappa-opioid receptor antagonist, had no significant effect on the antinociceptive effect of dihydroetorphine (10 micrograms/kg i.p.) in both diabetic and non-diabetic mice. These results suggest that dihydroetorphine produces an antinociceptive effect through the activation of both mu 1- and mu 2-opioid receptors in mice. Furthermore, the reduction in dihydroetorphine-induced antinociception in diabetic mice, as compared with non-diabetic mice, may be due to the hyporesponsive to supraspinal mu 1-opioid receptor-mediated antinociception in diabetic mice.

Analgesia↗

PubMed1995

The D3-receptor agonist (+/-)-7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) attenuates morphine-induced hyperlocomotion in mice.

The effects of the D3-agonist (+/-)-7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) on morphine-induced hyperlocomotion were investigated in mice. 7-OH-DPAT (0.01-0.3 mg/kg s.c.) alone did not produce a significant locomotor activity in mice. Treatment with low doses of 7-OH-DPAT (0.1 and 0.3 mg/kg s.c.) attenuated morphine (10 and 20 mg/kg s.c.)-induced hyperlocomotion. The significant morphine-induced increase in dopamine (DA) metabolite levels, 3,4-dihydroxyphenylacetic acid and homovanillic acid in the limbic forebrain (nucleus accumbens and olfactory tubercle) was suppressed by 7-OH-DPAT. These results suggest that activation of the D3-receptor in the mesolimbic dopamine system may attenuate the expression of morphine-induced hyperlocomotion.

Animals↗

PubMed1995

Effects of a highly selective nonpeptide delta opioid receptor agonist, TAN-67, on morphine-induced antinociception in mice.

The effects of a potent and highly selective nonpeptide delta opioid receptor agonist, 2- methyl-4a alpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12a alpha- octahydroquinolino [2,3,3,-g] isoquinoline (TAN-67), on morphine-induced antinociception were examined using the warm-plate (51 degrees C) method. When a peptide delta 1 opioid receptor agonist, [D-Pen2, Pen5]enkephalin (DPDPE), was co-administered with i.c.v. morphine, low-dose morphine-induced antinociception was significantly increased. In contrast, i.c.v. co-administration of a peptide delta 2 opioid receptor agonist, [D-Ala2]deltorphin II (DELT), with morphine did not affect the morphine-induced antinociception. When morphine and TAN-67 were co-administered i.c.v., low-dose morphine-induced antinociception was significantly increased. Moreover, when TAN-67 and morphine were co-administered s.c., the morphine dose-response curve shifted to the left and the ED50 value of morphine decreased. These effects DPDPE and TAN-67 were antagonized by the delta opioid receptor antagonist naltrindole (NTI) and the delta 1 opioid receptor antagonist 7-benzylidenenaltrexone (BNTX) not by the delta 2 opioid receptor antagonist naltriben (NTB). Moreover, the mu opioid receptor antagonist beta-FNA also antagonized the effects of DPDPE and TAN-67. These results suggest that the effect of TAN-67 may result from the activation of central delta 1 opioid receptors, since the effect of TAN-67 was antagonized by NTI and BNTX, but not NTB. Furthermore, since pretreatment with beta-FNA also antagonized the effects of both DPDPE and TAN-67, a beta-FNA-sensitive site, i.e. a mu-delta complex site, may play an important role in the modulation of morphine-induced antinociception.

Analgesics↗

PubMed1995

Sertindole antagonizes morphine-, cocaine-, and methamphetamine-induced place preference in the rat.

The motivational effect of sertindole, a limbic selective antipsychotic drug, was investigated in rats using a non-biased conditioned place preference method which could reliably detect the reinforcing effects of morphine, cocaine and methamphetamine. Sertindole (0.01-1.0 mg/kg, s.c.), like haloperidol and fluphenazine, produced neither place preference nor place aversion. However, sertindole, at a dose of 1.0 mg/kg, s.c., completely abolished the place preferences induced by morphine (8.0 mg/kg, i.p.), cocaine (4.0 mg/kg, i.p.) and methamphetamine (2.0 mg/kg i.p.). These results strongly suggest that sertindole itself does not induce a rewarding effect and may have therapeutic value in the treatment of drug abuse.

Animals↗

PubMed1995

Effect of naltrindole on the development of physical dependence on morphine in mice: a behavioral and biochemical study.

The effect of pretreatment with a delta opioid receptor antagonist, naltrindole (NTI), on the development of physical dependence on morphine was investigated in mice. Several withdrawal signs, an increase in cortical noradrenaline (NA) turnover and a decrease in dopamine (DA) turnover in the limbic forebrain were observed following naloxone challenge in morphine-dependent mice. Pretreatment with NTI (0.3-5 mg/kg, s.c.) during chronic morphine treatment dose-dependently suppressed the behavioral and biochemical changes after withdrawal. The blocking effects of NTI suggest that delta opioid receptors may play a significant role in modulating the development of physical dependence on morphine.

Animals↗

PubMed1995

Plant cell and tissue culture: alternatives for metabolite production.

Plant cell culture systems represent a potential renewable source of valuable medicinals, flavours, essences and colourants that cannot be produced by microbial cells or chemical syntheses. However, only a few cultures produce these compounds in commercially useful amounts. The low productivities are associated with our poor understanding of the biochemistry of these systems. Recent advances in molecular biology, enzymology, physiology and fermentation technology of plant cell cultures suggest that these systems will become a viable source of important natural products. This review examines the sate of the art of production of medicinal plant secondary metabolites by plant cell cultures.

Journal Article↗

PubMed1995

Characteristics of muscarinic cholinoceptors in airways of antigen-induced airway hyperresponsive rats.

The antagonist and agonist binding sites of muscarinic receptors were investigated by using membrane preparations of airways from nonsensitized normal control, sensitized control and repeatedly antigen challenged rats. The in vitro bronchial responsiveness to ACh was markedly increased in repeatedly antigen challenged group but not in sensitized control group. No significant difference was observed in receptor density and antagonist affinity among these three groups. The affinity of ACh for high-affinity agonist binding sites of repeatedly antigen challenged group was much greater than those in the other groups; the affinity significantly reduced in the presence of GTP gamma S. We concluded that enhanced G protein level might be involved in inducing airway hyperresponsiveness in rats.

Acetylcholine↗

PubMed1995

Anti-A and/or anti-B is not detectable in some patients who underwent ABO-incompatible bone marrow transplantation.

BACKGROUND: Recently, anti-A and/or anti-B produced by B cells from donor marrow could not be detected for more than 20 weeks in some patients who had undergone ABO-incompatible bone marrow transplantation (BMT). STUDY DESIGN AND METHODS: Twelve to 72 weeks after 11 patients underwent ABO-incompatible BMT, titers of anti-A and anti-B were assayed, A and B antigens were identified by routine methods and flow cytometry, direct and indirect antiglobulin tests were performed, and the red cell antibody was eluted. RESULTS: In some patients who underwent ABO-incompatible BMT, anti-A and/or anti-B produced by the B cells from the donor marrow could not be detected after BMT when red cells taken from the patients before BMT carried the corresponding antigen--that is, when hematopoiesis had already changed the cells to the donor's type according to ABO blood typing. Furthermore, some blood samples from those patients gave positive results in direct antiglobulin tests. Blood typing of patients after BMT showed mixed-field agglutination. In one patient, the half-life of red cells assayed with 51Cr was 22.4 days (30.0 +/- 4.0 days for normal controls). CONCLUSION: Although many hypotheses could be considered to explain the present data, the possibility is proposed that anti-A and/or anti-B in the sera must have been consumed in some patients who underwent ABO-incompatible BMT. This may lead to problems such as difficulty of ABO typing, positive direct antiglobulin tests, and a relatively short life span of red cells.

ABO Blood-Group System↗

PubMed1995

Clonal analysis of peripheral blood and haemopoietic colonies in patients with aplastic anaemia and refractory anaemia using the polymorphic short tandem repeat on the human androgen-receptor (HUMARA) gene.

The clonalities in white blood cells (WBC) of blood and nucleated bone marrow cells from patients with refractory anaemia and aplastic anaemia were examined by polymerase chain reaction (PCR) methods using the polymorphic short tandem repeat (STR) on the human androgen-receptor gene (HUMARA). Peripheral blood samples were obtained from 12 female patients, six with aplastic anaemia (AA) and six with refractory anaemia (RA). Peripheral blood was fractionated into granulocytes, lymphocytes, T lymphocytes and B lymphocytes. DNA was extracted from each fraction. Bone marrow samples were obtained from seven female patients (three with AA and four with RA). Sorted CD34 positive cells were cultured in a semisolid culture system. DNA was extracted from a 14-day haemopoietic colony. The clonal pattern was assessed using HUMARA gene STR polymorphism and the differential methylation pattern of nearby cytosine residues by PCR methods. Four of six (67%) AA and two of six (33%) RA patients had a monoclonal proliferating pattern in their granulocytes. The ratio of the numbers of minority colonies per majority colonies (m/M ratio) was examined for seven patients (three AA and four RA). In patients who had a clonal haemopoietic pattern in peripheral WBC the ratio was under 0.4 but not zero. In contrast, patients exhibiting a polyclonal pattern had an m/M ratio above 0.8. We concluded that some normal or heterogenous haemopoietic clones, not only MDS but also AA, may remain in the bone marrow, although almost all colonies were derived from a single pathogenic clone when the clonality pattern exhibited monoclonality in peripheral blood analysis.

Adult↗

PubMed1995

Inhibition of neutral endopeptidase increases airway responsiveness to ACh in nonsensitized normal rats.

The effects of sensory neuropeptides on the airway responsiveness to acetylcholine (ACh) were investigated in normal nonsensitized rats. The airway responsiveness to inhaled ACh was significantly increased after treatment with neurokinin A (NKA; 0.001%) or substance P (SP; 0.01%) aerosol in the presence of the neutral endopeptidase (NEP) inhibitor. NKA had a more potent effect than SP. Interestingly, the intravenous treatment with NEP inhibitor alone also induced airway hyperresponsiveness (AHR) to inhaled ACh. This AHR was significantly attenuated by pretreatment with a nonselective NK-receptor antagonist, [D-Pro2,D-Trp7,9]SP, systemic capsaicin, or bilateral cervical vagotomy, indicating that decreased NEP activity results in accumulation of endogenous sensory neuropeptide(s) and enhancement of vagal reflex to cause AHR. The airway responsiveness to ACh of isolated left main bronchus was also increased after treatment with 10(-6) M NKA, but not SP, together with 10(-6) M phosphoramidon. This in vitro AHR to ACh induced by phosphoramidon plus NKA was significantly attenuated by pretreatment with 10(-6) M tetrodotoxin. These findings suggest that overaccumulated sensory neuropeptides, especially NKA, may enhance the probability of transmitter release, probably via NK2 receptors, and that the enhanced transmitter release might be involved in AHR in rats.

Acetylcholine↗