Biomedical subjects

T Miyamae

Publications and source records attributed to T Miyamae.

At least 55 records · Page 3Linked to original sources

PubMed1997

Anticoagulant activity of the novel thrombin inhibitor 1-butyl-3-(6,7-dimethoxy-2-naphthylsulfonyl) amino-3-(3-guanidinopropyl)-2-pyrrolidinone hydrochloride.

1-Butyl-3-(6,7-dimethoxy-2-naphthylsulfonyl)amino-3-(3-guanidin opropyl)-2-pyrrolidinone hydrochloride (CAS 173440-64-7, SPI-501), which has highly selective thrombin-inhibitory activity, caused a concentration-dependent increase in the time taken for coagulation induced by thrombin in rabbit plasma. The IC50 of SPI-501 was 1.7 mumol/l. Argipidine also prolonged coagulation time and its activity was one order of magnitude greater than that of SPI-501. SPI-501 and argipidine caused dose-dependent increases in the activated partial prothrombin time (APTT) and prothrombin time (PT) of rat plasma. When APTT and PT were measured, IC50 values of SPI-501 were 38.0 and 18.5 mumol/l and those of argipidine, 1.4 and 1.9 mumol/l, respectively. Intravenous administration of SPI-501 (10 and 30 mumol/kg) and argipidine (1 and 3 mumol/kg) prolonged both APTT and PT in rats. While SPI-501 was less potent than argipidine, the durations of the effects of both were the same.

Animals↗

PubMed1997

Antithrombotic effects of 3-([1:1',2':1"]-3'-terphenyl)propanol in animals.

3-([1:1',2':1"]-3'-Terphenyl)propanol (CAS 186835-06-3, F050) and acetylsalicylic acid (ASA) inhibited platelet aggregation induced by CaCl2, arachidonic acid, collagen, adenosine diphosphate (ADP) and thrombin in guinea pigs, rabbits and rats in vitro. However, F050 had a wider spectrum of actions than ASA. Orally administered F050 inhibited platelet aggregation ex vivo. F050 significantly reduced the thrombus formation in the extracorporeal circulation thrombosis model in guinea pigs. It inhibited erythrocyte hemolysis induced by hypotonic NaCl, while ASA did not. F050, but not ASA, inhibited increases in platelet [CA2+]i caused by thrombin in guinea pigs. F050 is a parent compound that will facilitate the development of an orally active drug for the treatment of thrombotic diseases.

Animals↗

PubMed1997

[Comparative studies of airway deposition of 99mTc-DTPA aerosol particles among 4 different nebulizers by pulmonary scintillation method].

The inhalation therapy is one of the important treatment of bronchial asthma. The effectiveness of the therapy, however, is different depending on the size of particles produced by each inhalation equipment. Therefore, we have tried to clarify the relationship between the size of inhaled particles and the deposition rate in the lung by using different types of equipment. Four different equipments, Nishou, Pari-Boy, Pari-Master and Atom Soniclizer 905 were used. 99mTc-DTPA was dissolved in physiological saline and was inhaled for evaluation of "deposition" rate in the lung. The deposition rates by Nishou, Pari-Boy, Pari-Master and Atom Soniclizer 905 were 10.4 +/- 5.8%, 27.5 +/- 14.5%, 28.5 +/- 6.5%, and 31.1 +/- 6.8%, respectively. Most of 99mTc-DTPA inhaled was observed in oral cavity. The deposition in the lung by Nishou was significantly reduced compared to other three nebulizers. Those three were evaluated as appropriate equipments for the treatment. The average size of particles in an airsol by those three equipments was less than 5 microns. The study suggests that the size of "particles" in an airsol is very important factor for the inhalation therapy.

Adult↗

PubMed1997

L-DOPA cyclohexyl ester is a novel stable and potent competitive antagonist against L-DOPA, as compared to L-DOPA methyl ester.

We explore stable potent competitive antagonists against L-DOPA. In anesthetized rats, DOPA cyclohexyl ester (DOPA CHE) (30-100 ng) microinjected in depressor sites of the nucleus tractus solitarii dose-dependently shifted the dose-response-curve for L-DOPA (18-300 ng) to the right, with DOPA CHE (100 ng)-induced slight reduction of the maximum response. DOPA methyl ester (DOPA ME) at 100 ng also produced competitive antagonism. Antagonistic activity of DOPA CHE (100 ng) was similar to that of DOPA ME (300 ng). DOPA CHE is suitable for the purpose of screening.

Animals↗

PubMed1996

Ventral tegmental injection of nicotine induces locomotor activity and L-DOPA release from nucleus accumbens.

Effects of nicotine systemically or locally on locomotor activity and L-3,4-dihydroxyphenylalanine (L-DOPA) release were studied using microdialysis in the nucleus accumbens of freely moving rats. The basal L-DOPA release was Ca2(+)-dependent and tetrodotoxin-sensitive. Systemic nicotine (1 mg/kg s.c.) increased locomotor activity and L-DOPA release preferentially in the nucleus accumbens as compared with the striatum. Injection of nicotine (30 micrograms) into the ventral tegmental area increased locomotor activity and L-DOPA release from the nucleus accumbens. These increases were antagonized by prior injection of mecamylamine into the ventral tegmental area. Nicotine induces locomotor activity and L-DOPA release from the nucleus accumbens via nicotinic receptors in the ventral tegmental area. The release may be relevant to behavioral actions of nicotine.

Animals↗

PubMed1996

Depressor action of L-threo-dihydroxyphenylserine in the rat nucleus tractus solitarii.

Microinjections of L-threo-dihydroxyphenylserine (L-threo-DOPS, 0.1-3 ng), a synthetic precursor amino acid of noradrenaline, into the medial area of the nucleus tractus solitarii produced dose-dependent depressor and bradycardic responses in anesthetized rats treated with or without i.p. 3-hydroxybenzylhydrazine, a central inhibitor of L-aromatic amino acid decarboxylase. D-threo-DOPS (3 ng) produced no effect. L-Dihydroxyphenylalanine (L-DOPA) methyl ester (1 microgram), a competitive antagonist of L-DOPA, microinjected into the nucleus tractus solitarii, blocked the depressor and bradycardic responses to L-threo-DOPS itself produces vasodepressor actions without its conversion to noradrenaline, probably via a recognition site for L-DOPA in the rat nucleus tractus solitarii.

Animals↗

PubMed1996

Further search for small molecular inactivants capable of eliciting respiratory mucosal immunogenicity by modifying Sendai virus core RNA.

Five groups of 32 chemicals were examined regarding their immunological functions as modifier inactivants to make inactivated Sendai nasal vaccine using a contact exposure experiment, direct immunofluorescent method, and serum HI titer. (1) Five of the nine reactive groups of reactive dyes (2-chloropyridine, 2, 4, 6-trichloropyrimidine, vinylsulfonic acid, epichlorohydrin and beta-chloroethylamine) induced complete or almost complete defense in the entire respiratory tract, and the four other vaccines brought about slight infection in the respiratory tracts. There was no marked rise in serum HI titers post-exposure, despite uneven development. (2) Of the four sizable substituted AS naphthol vaccines, naphthol AS-IRG and AS-G vaccines elicited nearly complete defense, but the two other vaccines, inactivated with more elongated molecules, invited rare and successive infections. The three immune groups produced invariably high serum HI titers. (3) Of the six naphthalene derivative vaccines, two (3-hydroxy-2-naphthoic acid methylester and 2-naphthol-6-sulfonic acid) induced complete or almost complete protection. But two vaccines brought about less protection, and the remaining two vaccines caused heavy infections. (4) Of the six benzene derivative vaccines, both m-nitrobenzenesulfonic acid and isatoic anhydride induced complete protection. Three vaccines permitted slight infections but 2, 4, 6-trinitrobenzenesulfonic acid vaccine caused severe infection. (5) Of the seven food dye vaccines, only orange I induced complete or nearly complete defense, while the other dye vaccines were inferior. In effect, twelve inactivated Sendai nasal vaccines modified the ribose and/or phosphate groups of the virus core RNA through five groups of small-sized molecules with specially fixed side chains, and elicited complete or almost complete respiratory mucosal defense. The viral stabilization requiring the least alteration of the configuration will be involved in the chemical modification.

Administration, Intranasal↗

PubMed1996

In vitro antiplatelet activity of the carbinol analogue of ketoprofen, 3-(1-methyl-2-hydroxyethyl)-benzophenone.

3-(1-Methyl-2-hydroxyethyl)-benzophenone (F025) is a close structural analogue of ketoprofen, in which the carboxylic acid of ketoprofen is reduced to a carbinol moiety. The in vitro effects of F025 on platelet aggregation, cyclooxygenase and hypotonic NaCl-induced erythrocyte hemolysis were examined in comparison with those of ketoprofen. Although the inhibitory activity of F025 on collagen, arachidonic acid and ADP-induced platelet aggregation was between 2 and 20 times that of ketoprofen in healthy volunteers, guinea pigs, rabbits and rats, F025 had only one-tenth of the inhibitory action of ketoprofen on sheep seminal vesicle cyclooxygenase F025, but not ketoprofen, inhibited hypotonic NaCl-induced erythrocyte hemolysis in guinea pigs. The substantial antiplatelet activity of F025 may be due to membrane stabilization as well as to cyclooxygenase inhibition.

Animals↗

PubMed1995

Evidence for a metabostatic opioid kappa-receptor inhibiting pertussis toxin-sensitive metabotropic glutamate receptor-currents in Xenopus oocytes.

Glutamate evoked pertussis toxin-sensitive currents in Xenopus oocytes expressing metabotropic glutamate receptor subtype 1 (mGluR1) and exogenous Gi1 alpha. The mGluR1-currents were completely blocked by U-73122, a phospholipase C (PLC) inhibitor and by niflumic acid, a chloride channel blocker. In the oocyte further coinjected with poly(A)+ RNA from the guinea pig cerebellum, the mGluR1-currents were inhibited by U-50488H, an opioid kappa-agonist, and this inhibition was blocked by norbinaltorphimine, an opioid kappa-antagonist. These findings suggest that the mRNA encoding a novel subtype of opioid kappa-receptor which inhibits Gi1-PLC-mediated currents is present in guinea pig cerebellar poly(A)+ fractions.

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

PubMed1995

Loss of tonic neuronal activity to release L-DOPA in the caudal ventrolateral medulla of spontaneously hypertensive rats.

Experiments were designed to clarify whether a tonic L-DOPA system is altered in the caudal ventrolateral medulla (CVLM) of adult spontaneously hypertensive rats (SHR), compared to age-matched Wistar-Kyoto rats (WKY). By microdialysis in CVLM, basal L-DOPA release was constantly detectable and was lower in SHR than that in WKY. This release was reduced by tetrodotoxin perfusion (1 microM) in WKY to a basal level in SHR, whereas no modification occurred with tetrodotoxin in SHR. No difference of tyrosine hydroxylase and DOPA decarboxylase activities in the CVLM region was seen between the two strains. By microinjections into depressor sites of CVLM, L-DOPA (10-300 ng) or L-glutamate (3-300 ng) elicited dose-dependent depressor and bradycardic responses and greater depressor responses to both amino acids were seen at high doses in SHR, compared to WKY. Tonic neuronal activity to release L-DOPA is lost in the CVLM of adult SHR and this loss may contribute to maintenance of hypertension in SHR.

Animals↗

PubMed1995

Opioid mu- and kappa-receptor mediate phospholipase C activation through Gi1 in Xenopus oocytes.

In the Xenopus oocytes expressing mu- or kappa-opioid receptors, agonist-induced currents were observed only when the oocyte was coinjected with Gi1 alpha RNA and pretreated with K-252a, a potent inhibitor of protein kinases. The evoked currents were abolished by intracellular injection of EGTA or inositol 1,4,5-trisphosphate and the current-voltage relationship revealed that they are mediated through typical calcium-dependent chloride channels. These findings suggest that the mu- and kappa-receptors mediate phospholipase C activation through Gi1 alpha, and that these receptor mechanisms including downstream signalings might be inhibited by phosphorylation in vivo in the Xenopus oocyte.

Animals↗

PubMed1995

Altered tonic L-3,4-dihydroxyphenylalanine systems in the nucleus tractus solitarii and the rostral ventrolateral medulla of spontaneously hypertensive rats.

We have proposed that L-3,4-dihydroxyphenylalanine (L-DOPA) is a neurotransmitter in the central nervous system [Y. Misu et al. (1995) Adv. Pharmac. 32, 427-459]. L-DOPA as a probable neurotransmitter for the primary baroreceptor afferents tonically functions to mediate cardiodepressor control in the nucleus tractus solitarii and also tonically functions to mediate cardiopressor control in the rostral ventrolateral medulla of rats. We further attempted to clarify whether a transmitter-like L-DOPA system is altered in these areas of adult spontaneously hypertensive rats. By microdialysis in the left nucleus tractus solitarii area, the basal L-DOPA release was lower in spontaneously hypertensive rats than that in Wistar-Kyoto rats. This release was partially reduced by tetrodotoxin (1 microM) to the same absolute levels in the two strains. Tonic neuronal L-DOPA release is impaired in this nucleus of spontaneously hypertensive rats. This impairment is not secondarily due to decrease in formation or increase in decarboxylation of L-DOPA, since tyrosine hydroxylase activity was increased in spontaneously hypertensive rats, compared to Wistar-Kyoto rats, while no difference of L-aromatic amino acid decarboxylase activity was seen in the caudal dorsomedial medulla including the nucleus. L-DOPA (10-300 ng) microinjected into the nucleus produced dose-dependent hypotension and bradycardia. A maximum depressor response of spontaneously hypertensive rats to L-DOPA at higher doses was slightly greater than that of Wistar-Kyoto rats. On the other hand, in the left rostral ventrolateral medulla, the basal L-DOPA release was higher in spontaneously hypertensive rats than that in Wistar-Kyoto rats. This release was also partially reduced by tetrodotoxin to the same absolute levels in the two strains. Tonic neuronal L-DOPA release is enhanced in spontaneously hypertensive rats. This enhancement seems to include partially a decrease in decarboxylation of L-DOPA, since L-aromatic amino acid decarboxylase activity was decreased in spontaneously hypertensive rats compared to Wistar-Kyoto rats, while no difference in tyrosine hydroxylase activity was seen. L-DOPA (10-600 ng) produced dose-dependent hypertension and tachycardia. Importantly, a pressor response of spontaneously hypertensive rats to L-DOPA at lower doses was slightly greater than that of Wistar-Kyoto rats. L-DOPA seems to play a transmitter-like role in blood pressure regulation at levels of the nucleus tractus solitarii and rostral ventrolateral medulla in rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1995

Altered basal release and depressor effect of L-DOPA in the nucleus tractus solitarii of spontaneously hypertensive rats.

1. L-DOPA as a probable neurotransmitter of baroreceptor afferents functions as a tonic to mediate cardiodepressor control in the nucleus tractus solitarii (NTS). We attempted to clarify further whether a transmitter-like L-DOPA system is altered in NTS of adult spontaneously hypertensive rats (SHR). 2. By microdialysis of left NTS area, the basal L-DOPA release was lower in SHR than in Wistar-Kyoto (WKY) rats. This release was partially inhibited by tetrodotoxin (TTX, 1 mu mol/L) to a similar degree in both strains. TTX-sensitive L-DOPA release was lower in SHR than in WKY. 3. L-DOPA (10-300 ng) and L-glutamate (3-100 ng) microinjected into left NTS produced dose-dependent hypotension and bradycardia. No difference of responses to L-glutamate was seen in either strain. However, depressor but not bradycardic responses to L-DOPA at higher doses were slightly greater in SHR than in WKY. 4. In caudal dorsomedial medulla including NTS, tyrosine hydroxylase activity was increased in SHR compared to WKY, while there was no difference in either strain of L-aromatic amino acid decarboxylase activity. 5. Impaired tonic neuronal activity to release L-DOPA in NTS may be involved in the maintenance of hypertension in SHR. An increase in sensitivity of a recognition site for L-DOPA seems to occur as a compensatory mechanism for impairment of the neuronal activity.

Animals↗

PubMed1995

Altered basal release and pressor effect of L-DOPA in the rostral ventrolateral medulla of spontaneously hypertensive rats.

1. Transmitter-like L-DOPA functions as a tonic to produce postsynaptic cardiopressor responses in the rostral ventrolateral medulla (RVLM) of rats. We attempted to clarify whether a transmitter-like L-DOPA system is altered in the RVLM of spontaneously hypertensive rats (SHR) to maintain the hypertension. 2. By microdialysis of left RVLM area, the basal L-DOPA release was higher in SHR than in Wistar-Kyoto (WKY) rats. This release was partially inhibited by tetrodotoxin (TTX, 1 mu mol/L) to a similar degree in both strains. TTX-sensitive L-DOPA release was higher in SHR than in WKY. 3. L-DOPA (10-600 ng) and L-glutamate (10-300 ng) microinjected into left RVLM produced dose-dependent hypertension and tachycardia. Pressor but not tachycardiac responses to L-DOPA at lower doses were slightly greater in SHR than in WKY, whereas no difference to L-glutamate was observed in either strain. 4. In RVLM regions, there was no difference of tyrosine hydroxylase activity in SHR or WKY; however, L-aromatic amino acid decarboxylase activity was lower in SHR than in WKY. 5. Enhanced presynaptic neuronal L-DOPA release, including a decrease in decarboxylation and sensitization of postsynaptic pressor sites to L-DOPA in RVLM, may be involved in the maintenance of hypertension in SHR.

Animals↗

PubMed1995

Calcium-induced platelet aggregation in washed platelets from guinea pigs.

The present study investigated the effects of extracellular calcium on washed platelets of guinea pigs, rabbits, rats and humans. CaCl2 without agonists induced platelet aggregation in guinea pigs and rabbits, but not in rats or humans. CaCl2 increased platelet [Ca2+]i in Fura-2-loaded guinea pig platelets. Calcium-induced platelet aggregation was inhibited by W-7 (a calmodulin antagonist), aspirin, indomethacin, TMB-8 (an inhibitor of intracellular Ca2+ release) and also nicardipine (a calcium antagonist). These data suggest that CaCl2-induced platelet aggregation is mediated by calmodulin, cyclooxygenase and other, as yet unknown, mechanisms.

Animals↗

PubMed1995

Altered L-DOPA systems for blood pressure regulation in the lower brainstem of spontaneously hypertensive rats.

Recent findings have enhanced our understanding of the roles played by the L-DOPA system in the baroreceptor reflex and in blood pressure regulation in the lower brainstem. L-DOPA is probably a neurotransmitter of primary baroreceptor afferents terminating in depressor sites of the nucleus tractus solitarii (NTS). It also seems to be a neurotransmitter in depressor sites of the caudal ventrolateral medulla (CVLM) and in pressor sites of the rostral ventrolateral medulla (RVLM) of normotensive Wistar rats. We have explored whether or not presynaptic and postsynaptic functions of the L-DOPA system in these areas are altered to maintain hypertension in adult spontaneously hypertensive rats, as compared with age-matched Wistar Kyoto rats. In this review article, we survey the roles of the L-DOPA system in the baroreceptor reflex and in blood pressure regulation in the rat lower brainstem.

Animals↗

PubMed1995

Protein kinase C involvement in homologous desensitization of delta-opioid receptor coupled to Gi1-phospholipase C activation in Xenopus oocytes.

We have developed the coexpression system of both delta-opioid receptor (DOR1) and M2-muscarinic receptor (M2) which mediate agonist-evoked currents due to common post-receptor mechanisms including Gi1 and phospholipase C (PLC) activation in Xenopus oocytes reconstituted with Gi1 alpha. The DOR1-currents by 100 nM D-Ser2-leu-enkephalin-Thr6 (DSLET) were selectively desensitized by 10 nM phorbol 12-myristate 13-acetate (PMA). The PMA-desensitization of DSLET-currents was abolished in the presence of calphostin C, a protein kinase C inhibitor, or reversed by an intracellular injection of calcineurin, a protein phosphatase 2B. When a higher concentration (3 microM) of DSLET was used, DSLET-currents were rapidly desensitized by repeated challenges of DSLET itself. However, repeated challenges of 10 microM ACh caused no influence on such DSLET- or M2-currents. The desensitization of DSLET-currents was selectively reversed by protein kinase C inhibitors. Similar results were also obtained with various delta-opioid agonists. These results suggest that protein kinase C is involved in the homologous desensitization of delta-opioid receptors.

Animals↗

PubMed1994

Protein kinase inhibitor potentiates opioid delta-receptor currents in Xenopus oocytes.

In Xenopus oocytes injected with RNA coding for the delta-opioid receptor a small chloride current was evoked by [D-Ala2,Ser5]leucine-enkephaline-Thr6 (DSLET), a delta 2-opioid agonist. The evoked currents were rapidly reduced upon repeated challenges of DSLET. When Gil alpha RNA was co-injected into the oocyte, the evoked currents were increased 3.8-fold and became constant after at least three repeated challenges. In oocytes injected with RNAs coding for delta-receptor and Gil alpha, pretreatment with K-252a, a potent inhibitor of protein kinases, further potentiated the delta-receptor-mediated current responses, compared with those without the inhibitor. These results suggest that signalling involving the delta-opioid receptor is inactivated through in vivo phosphorylation in the Xenopus oocyte.

Analgesics↗