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Biomedical subjects

K Shuto

Publications and source records attributed to K Shuto.

At least 73 records · Page 4Linked to original sources
PubMed1988

Pharmacological actions of benidipine hydrochloride in several isolated smooth muscles and myocardium.

Using various isolated smooth muscles and myocardium, the calcium antagonistic effect of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)- 1,4-dihydropyridine-3,5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049), and its specificity were examined. Furthermore, the in vitro duration of action and the antispasmodic actions in coronary arteries were investigated in comparison with those of nifedipine, verapamil and diltiazem. 1. Ca antagonisms of KW-3049 When the Ca antagonistic effect of KW-3049 was investigated, for which the contractile responses to KCl in isolated mesenteric arteries in rabbits were taken as an indicator, the activity of KW-3049 was of about the same degree as nifedipine and approx. 30 times greater than those of verapamil and diltiazem. On the other hand, the negative inotropic action in isolated atria in rabbits was weaker than that of nifedipine. 2. Influences on responses to various agonists From the investigations using various isolated organs, it was evident that KW-3049 had neither agonistic nor antagonistic actions or very weak actions on the following receptors: alpha 1, alpha 2, beta 1, beta 2, H1, H2, muscarinic acetylcholine, 5HT2, angiotensin II, and prostaglandin F2 alpha. 3. Duration of in vitro actions Inhibitory actions of KW-3049 on 55 mmol/l-induced contractions in isolated mesenteric arteries in rabbits persisted even 180 min after the removal of drug solution and the repeated wash-out of tissues. On the other hand, those of nifedipine, verapamil and diltiazem disappeared within 60 to 120 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

[Clinical and pharmacokinetics evaluation of flomoxef in pediatrics].

Flomoxef (FMOX, 6315-S), a new parenteral oxacephem antibiotic was investigated for its clinical efficacy and pharmacokinetics. The results obtained are summarized below. 1. Twenty-eight patients were treated with 39-152 mg/kg per day of FMOX by intravenous administration. Diagnosis of patients were pneumonia in 15 patients, acute upper respiratory tract infection in 5, acute enterocolitis in 3, urinary tract infection in 2 and cholangitis, suppurative lymphadenitis and suspicious sepsis in 1 patient each. Clinical effect was excellent in 7 cases, good in 8, fair in 5, poor in 2 and 6 cases were excluded because therapy periods were too short and other antibiotics were used together. Efficacy rate was 68% and the rate of bacterial disappearance was 83%. 2. Rash was found in 5 cases and thrombocytosis was found in 1 out of 28 cases. However, no severe adverse reaction was encountered. 3. The peak serum level of FMOX was 51.0 micrograms/ml after 20 mg/kg of drip infusion for 30 minutes and the half-life was 17.2 minutes in alpha-phase and 58.2 minutes in beta-phase.

Adolescent↗
PubMed1986

MY336-a, a novel beta-adrenergic receptor antagonist produced by Streptomyces gabonae.

Streptomyces gabonae KY2234 was found to produce a new compound, MY336-a, which bound to beta-adrenergic receptor. The compound was isolated from the fermentation broth of KY2234. MY336-a showed a high affinity for the beta-receptor, labeled with [3H]dihydroalprenolol in the membrane fractions of rat heart (beta 1-adrenergic receptor) or lung (beta 2-adrenergic receptor), whereas the compound bound very weakly to alpha-adrenergic receptor, labeled with [3H]dihydroergokryptine in rat brain. the inhibition constants (Ki) of the compound were 0.73 and 0.14 microM for the beta-receptors of heart and lung, respectively. 5'-Guanylylimidodiphosphate (Gpp(NH)p) did not alter the affinity of the beta-receptors for MY336-a. In isolated guinea-pig atria, MY336-a produced an inhibition of the positive chronotropic and inotropic effects of isoproterenol. MY336-a also antagonized the relaxation of tone induced by isoproterenol in isolated guinea-pig trachea. No partial agonistic activity was detected in MY336-a in the isolated atria and trachea. In anaesthetized dogs, MY336-a (1 mg/kg, iv) exerted negative inotropic action (left ventricular dp/dt max, -32.6%).

Adrenergic beta-Antagonists↗
PubMed1986

K-26, a novel inhibitor of angiotensin I converting enzyme produced by an actinomycete K-26.

A novel inhibitor of angiotensin I converting enzyme (ACE), designated K-26, was isolated from the broth filtrate of an actiomycete K-26. K-26 is a water soluble, acidic peptide composed of an equal mol of L-isoleucine, L-tyrosine and 1(R)-1-amino-2-(4-hydroxyphenyl)-ethylphosphonic acid. The IC50 of K-26 for ACE inhibition was 6.7 ng/ml when hippuryl-L-histidyl-L-leucine was used as a substrate of ACE. K-26 possesses hypotensive activity in vivo.

Actinomycetales↗
PubMed1985

Involvement of disulfide-sulfhydryl interaction in anti-platelet actions of KF4939.

We studied on the role of an intramolecular disulfide bond of KF4939 in its anti-platelet actions by using rabbit platelets. The inhibitions of aggregation of platelet-rich plasma (PRP) and washed platelets, and of malondialdehyde production in thrombin-stimulated platelets by KF4939 were counteracted by pretreatment with sulfhydryl compounds, glutathione, 1-cysteine and dithiothreitol. A reduced compound of KF4939 (Red-KF4939) showed nearly equal anti-aggregating activities to those of KF4939 in PRP, it, however, showed low activities to inhibit platelet aggregation and thrombin -stimulated malondialdehyde production in washed platelet suspensions. In addition, the anti-aggregating action of Red-KF4939 was counteracted by pretreatment with sulfhydryl compounds, similarly to that of KF4939. Furthermore, when platelets were treated with KF4939, a significant decrease of protein-bound sulfhydryl groups was observed. We may conclude from these results that the intramolecular disulfide bond plays an essential role in anti-platelet actions of KF4939 and the interaction of the disulfide bond with protein-bound sulfhydryl groups may be involved in the mechanism of anti-platelet actions of KF4939.

Animals↗
PubMed1985

Interaction of 5-hydroxytryptamine and ketanserin in rat vas deferens subjected to low frequency field stimulation.

The interaction of 5-hydroxytryptamine (5HT) and ketanserin was investigated in isolated rat vas deferens. Ketanserin (10(-7) M) almost completely abolished the phasic and the following rhythmic contractions induced by 5HT, whereas the inhibition by prazosin (10(-6) M) or methysergide (10(-6) M) of 5HT-induced contractions were incomplete. The amplitude of twitch contractions of vas deferens subjected to low frequency (0.1 Hz) field stimulation were substantially unchanged by 5HT (10(-7)-10(-5) M) per se. After pretreatment of the tissue with ketanserin (10(-8)-10(-6) M), 5HT, in a concentration-dependent manner, attenuated the amplitude of twitch contractions. Such attenuation of the amplitude was not observed after pretreatments with methysergide (10(-8)-10(-6) M) or prazosin (10(-7)-10(-5) M). The 5HT-induced inhibition of twitch contractions in the presence of ketanserin was not antagonized by phentolamine, propranolol, methysergide, morphine, promethazine, cimetidine, atropine or indomethacin. It is suggested that 5HT has dual (excitatory and inhibitory) effects upon nerve transmission of rat vas deferens, and only the excitatory effect is suppressed by ketanserin.

Animals↗
PubMed1985

Inhibitory effects of oxatomide on several activities of SRS-A and synthetic leukotrienes in guinea-pigs and rats.

Effects of oxatomide, an orally active anti-allergic drug, on several activities of slow reacting substance of anaphylaxis (SRS-A) and synthetic leukotrienes (LT) C4, D4 and E4 were investigated. In addition, such activities of oxatomide were compared with those of FPL-55712. Oxatomide, at a concentration of 3 X 10(-8) M or higher, inhibited the phasic contractions of isolated guinea-pig ileum induced by partially purified SRS-Agp and SRS-Arat which were anaphylactically generated from guinea-pig lung fragments and rat peritoneal cavities, respectively. The 50% inhibitory concentrations (IC 50) of oxatomide to the contractions by SRS-Agp and SRS-Arat are 2.7 +/- 0.9 X 10(-7) M and 1.6 +/- 0.3 X 10(-7) M, respectively. Oxatomide also inhibited the LTC4, LTD4, histamine or serotonin-induced contractions of ileum. FPL-55712, a specific SRS-A antagonist, inhibited SRS-Agp, SRS-Arat, LTC4 or LTD4-induced contractions at concentrations ranging from 10(-9) M to 10(-6) M without affecting histamine and serotonin responses. Oxatomide produced dose-dependent relaxations of isolated guinea-pig tracheal and lung parenchymal strips precontracted with LTD4 and histamine. Oxatomide, at doses 10 and 30 mg/kg (p.o.), inhibited significantly the increase in vascular permeability produced by LTC4, LTE4, histamine and serotonin in rats. These results suggest that, although less effective and less selective as compared with FPL-55712, oxatomide exerts inhibitory effects on SRS-A activities, and that such effects could partly explain the anti-allergic effects of the compound.

Animals↗
PubMed1984

Inhibition of thromboxane A2-induced vasocontraction by KF4939, a new anti-platelet agent, in rabbit mesenteric and dog coronary arteries.

The effect of a new anti-platelet agent, KF4939, on thromboxane A2 (TXA2)-induced vasocontraction was studied in superfused rabbit mesenteric and dog coronary arteries, in comparison with the effects on the contractions evoked by KCl, noradrenaline, serotonin, angiotensin II and histamine. The calcium sources involved in the TXA2-induced vasocontraction were also examined. The TXA2-induced contraction of the rabbit mesenteric artery was partly attenuated after exposure to the calcium-free medium, but was not attenuated by nifedipine. The TXA2-induced contraction of the dog coronary artery was markedly attenuated by nifedipine. These results indicate that TXA2 utilizes both intracellularly stored calcium and an extracellular source of calcium for its vasocontraction, and the voltage-dependent calcium channel plays an important role in the dog coronary artery, but in the rabbit mesenteric artery. KF4939 inhibited the TXA2-induced contraction in both arteries. In the rabbit mesenteric artery, three times and more higher concentration than that to inhibit TXA2-induced one were required to inhibit other agonist induced contractions, KF4939 caused no alteration in the KCl-induced contraction of both arteries. Thus, KF4939 seems to be a selective inhibitor of TXA2-induced vasocontraction, and the receptor-linked mechanism may be a possible site of the TXA2 antagonistic action of KF4939.

Angiotensin II↗