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Biomedical subjects

A Kiyomoto

Publications and source records attributed to A Kiyomoto.

17 recordsLinked to original sources
PubMed1979

Effect of diltiazem on insulin secretion. II. Experiments on perfused rat pancreas, anesthetized dogs and conscious rats.

Effect of diltiazem on insulin secretion was investigated in the perfused rat pancreas. Experiments were also carried out in anesthetized dogs and conscious rats with and without glucose loading. In the perfused rat pancreas, diltiazem reduced both glucose- and tolbutamide-induced insulin secretion and these effects of diltiazem were reversed with removal of the compound. Inhibition of the glucose-induced insulin secretion caused by diltiazem was counteracted by increasing the concentration of calcium ion. In experiments on intact animals, diltiazem at vasoactive doses produced no significant influence on the basal level of plasma insulin or glucose-induced insulin secretion. These data taken together with findings in previously reported work suggest that diltiazem reduces insulin secretion from pancreatic B-cells in vitro possibly by the calcium-antagonistic property, while the compound exhibits practically no inhibitory action on the insulin secretion in vivo.

Anesthesia↗
PubMed1978

[Bronchodilating action of (--)-1-(3, 4, 5-trimethoxybenzyl)-7-hydroxy-1, 2, 3, 4-tetrahydroisoquinoloine HCl (l-MTI) (author's transl)].

Bronchodilating action of l-MTI was investigated by intravenous administration to anesthetized animals and the results were compared to those seen with isoproterenol. Bronchoconstriction was induced by histamine or serotonin. Under pentobarbital anesthesia, the bronchodilating activity of l-MTI was approx. 1/20 that of isoproterenol in cats and dogs, but less than 1/100 that of isoproterenol in monkeys and guinea pigs. The results indicate that the bronchodilating activity of l-MTI is variable and species dependent. It was demonstrated, however, that in guinea pigs, l-MTI did not produce any bronchodilating activity, when the animals were anesthetized with urethane. The absence of the bronchodilating response in animals under this anesthesia was also seen in vagotomized, adrenalectomized and reserpinized, norepinephrine-infused guinea pigs. On the contrary, l-MTI exhibited the bronchodilating action in reserpinized, pithed or hexamethonium-treated guinea pigs anesthetized with urethane. On th other hand, isoproterenol produced a bronchodilating action in all preparations mentioned above. It was also evident that l-MTI suppressed the bronchodilating action of isoproterenol in pentobarbital anesthetized guinea pigs. In addition, l-MTI increased the heart rate of guinea pigs with a low beating rate, but decreased it when the control rate was high. These results suggest that at least in guinea pigs, l-MTI acts as a partial agonist and that the effect of l-MTI on the bronchial system depends on the sympathetic tone and/or sympathetic bronchodilator reflex, as proposed by McCULLOCH ET AL. (9).

Adrenalectomy↗
PubMed1977

[Vasodilator action of (+/-)-1-(3, 4, 5-trimethoxybenzyl)-6-hydroxy-1, 2, 3, 4-tetrahydroisoquinoline hydrochloride (CV-705) in anesthetized dogs (author's transl)].

The vasodilator action of CV-705 was investigated in a number of vascular regions of anesthetized mongrel dogs and this action was compared with that of papaverine. When CV-705 was administered intravenously the vertebral, common carotid and internal carotid blood flow was increased considerably and was long-lasting. These effects were most remarkable among the regions tested. Femoral, aortic and coronary blood flow were also increased. On the other hand, the blood flow through superior mesenteric artery and portal vein increased only slightly. Renal blood flow was decreased slightly after an intravenous administration, whereas an increase was observed after an intra-arterial administration. Such a regional distribution of blood flow after CV-705 was quite similar to that observed with papaverine. CV-705 was well absorbed through the digestive tract. CV-705 given intravenously showed a weak hypotensive and positive chronotropic action. The increase in common carotid blood flow induced by intra-arterial administration of CV-705 was not affected by pre-treatment with atropine or triprolidine, but was partially suppressed by pre-treatment with propranolol. These results suggest that CV-705 has a papaverine-like action as well as a weak beta-adrenoceptor stimulating action, consequently a vasodilator action occurs.

Anesthesia↗
PubMed1977

Effects of diltiazem and lanthanum ion on the potassium contracture of isolated guinea pig smooth muscle.

Effects of diltiazem on K-induced contracture of the smooth muscle were examined in the isolated taenia coli and stomach strip of the guinea pig. Results were compared with those of lanthanum ion (La(3+)). K-contracture was evoked by isotonic K-Krebs solution. La(3+) inhibited K-contracture of the taenia coli and effects on the phasic response were found to be more remarkable than on the tonic response. After the removal of La(3+), the phasic response almost regained its normal magnitude, whereas the tonic response was significantly augmented. In contrast to the effects of La(3+), diltiazem inhibited the tonic response more markedly than the phasic response in both taenia coli and stomach strip. Inhibition of the phasic response was elicited, in association with decrease in the frequency of spike discharge during rapid depolarization of the membrane. The effects of diltiazem were completely reversed after washing out the compound. It is assumed that although both La(3+) and diltiazem inhibit the transmembrane influx of Ca(2+), additional mechanisms may differ.

Animals↗
PubMed1977

Effects of diltiazem on electrical and mechanical activities of isolated guinea pig taenia coli.

Effects of diltiazem on electrical and mechanical activities of isolated guinea pig taenia coli were studied by means of the double sucrose-gap method. In the spontaneously active preparations, diltiazem (2.2 X 10(-6) M) suppressed both electrical activity and isometric contraction, while electrical and mechanical activities evoked by the depolarizing current pulse were not affected at the concentration of 2.2 X 10(-6) M. In the presence of 2.2 X 10(-5) M diltiazem, the evoked contractile force and the number of repetitive firings during depolarization were reduced, whereas the single spike was almost unchanged or somewhat inhibited. At 2.2 X 10(-4) M diltiazem, both electrical and mechanical activities were almost abolished. The contractile force and single spike suppressed by diltiazem were partly reversed by the addition of 5 mM CaCl2. There was little significant change in membrane potential and membrane resistance. Similar but somewhat weaker effects were observed when NaCl was replaced with sucrose. In some preparations, 2.2 X 10(-4) M diltiazem reduced the contractile force without significant influence on the electrical activity in Na+-free Locke solution. CoCl2 (3 mM) inhibited the evoked activities in both normal and Na+-free solutions. Possible mechanisms for the relaxing effects of diltiazem on isolated guinea pig taenia coli were discussed.

Animals↗
PubMed1977

Effect of diltiazem on insulin secretion. I. Experiments in vitro.

Effect of diltiazem on glucose-induced insulin secretion was investigated in the rat islets of Langerhans isolated by a collagenase digestion technique. It was found that B-cells, main constituents of isolated islet preparations, had a well-preserved ultrastructural appearance immediately following isolation or after incubation with glucose or glucose and diltiazem. The islets released a large amount of insulin upon stimulation with glucose and CaCl2. Diltiazem (10(-6)-10(-4) M) produced a dose-related inhibition of glucose-induced insulin secretion and this effect was antagonized by the increase in extracellular concentration of CaCl2. The inhibitory effect of diltiazem on the insulin secretion was also counteracted by dibutyryl-3',5'-cyclic AMP or by theophylline. Among calcium-antagonists tested, nifedipine produced the most powerful inhibitory action on the insulin secretion, while the effect of verapamil was similar to or somewhat stronger than that of diltiazem. It was suggested that diltiazem may reduce the intracellular concentration of free calcium ion, thus causing an inhibitory effect on the glucose-induced insulin secretion by the isolated islets of Langerhans.

Animals↗
PubMed1976

Studies on the structure activity relationship of adrenergic beta-mimetic benzylamine derivatives.

Appropriately substituted benzylamine (BZA) derivatives, fragmented derivatives of tetrahydroisoquinolines, were found to be directly acting adrenergic beta-stimulants, exhibiting tracheal relaxing, positive chronotropic and free fatty acid (FFA) releasing activities. The chemical structures essential for manifestation of the beta-action were i) 3,4-dihydroxybenzylamine, ii) arylmethyl group at position alpha, iii) lower alkyl group on the N atom. The structure activity relationships of BZA-derivatives were almost similar to, but partly different from those of tetrahydroisoquinoline- and catecholamine-derivatives. The tracheal relaxing, positive chronotropic and FFA-releasing actions of alpha-(3,4,5-trimethoxybenzyl)-N-methyl-3,4-dihydroxybenzylamine, the most active compound in the BZA-derivatives tested, were approximately one-hundred, thirty and fifty times less active than those of ISO, respectively. These results indicate that this compound is beta1-selective, while trimetoquinol is beta2-selective.

Adipose Tissue↗
PubMed1976

Electrical and mechanical responses to diltiazem in potassium depolarized myocardium of the guinea pig.

Effects of diltiazem on the electrical and mechanical activities of guinea pig papillary muscle were investigated in K-rich Tyrode's solution (Kc1 12.7 mM). The electrical properties of cell membrane in K-rich solution were also examined in the ventricular muscle fibers. It was found that the overshoot as well as the maximum rate of rise (Vmax) of the action potential were highly sensitive to the extracellular concentration of CaC12 in K-rich solution. Vmax was also affected by NaC1. Diltiazem at a lower concentration (1.1 X 10(-7) M) caused a reduction in the contractile force of K-depolarized papillary muscle without producing significant changes in the resting and action potentials. In the presence of a higher concentration of diltiazem (1.1 X 10(-5) M), the contractile force decreased concurrently with the change in the action potential. Addition of CaC12 restored the original strength of contraction in parallel to the recovery of the action potential, especially in its overshoot and Vmax. From these results, it is inferred that diltiazem may decrease the contractile force of guinea pig papillary muscle either by interfering with the intrasmembrane calcium influx or by intracellularly reducing the free calcium ion concentration in the myoplasm.

Action Potentials↗
PubMed1976

Studies on the mode of antagonism between adrenergic beta-mimetics and beta-blocking agents (II). Analysis by the uptake saturation model.

Curves of experimentally plotted log (dose ratio-1) vs.-log [B] for the antagonism between adrenergic beta-mimetics, isoproterenol (ISO) and trimetoquinol (TMQ), and various beta-antagonists in relaxation of guinea-pig trachea could not be reasonably fitted to Schild's equation which has been commonly used in the analysis of drug-antagonism. Taking into consideration the saturable uptake process of the drug used herein, the equation presented in this paper fitted fairly well to the experimental curves and explains the following results: 1, TMQ was more strongly antagonized than ISO by all the blocking agents tested, that is, the apparent modes of antagonism were different between ISO and TMQ although they are considered to interact with the same receptor site. 2, The slope of the curve for a given antagonist markedly differed between ISO and TMQ. It is hypothesized that ISO is more easily taken up than TMQ. This was experimentally confirmed: i.e., ISO was potentiated about 8 fold by inhibiting the uptake process with dibenamine while TMQ was not. By pretreatment with dibenamine, the log (dose ratio-1) vs.-log [B] curve for the ISO-propranolol antagonism was shifted upward and superimposed with the theoretical curve of antagonism in which uptake of the agonist was neglected.

Adrenergic beta-Agonists↗
PubMed1975

Studies on mode of antagonism between adrenergic beta-mimetics and beta-blocking agents (I). Beta-blocking action of mescaline and its derivatives.

In order to clarify whether or not trimetoquinol (TMQ) and isoproterenol (ISO) interact with the same receptor, the pA2 values of propranolol (PR) and certain trimethoxybenzene derivatives were measured, using isolated guinea pig tracheal chains. Each of PR, mescaline (MES) and its derivatives gave almost the same pA2 values for TMQ and ISO. Introduction of an alkyl group into the N atom of MES increased the affinity to the receptor in the order of methyl and isopropyl as well as the structureactivity relationship of catecholamines, while that of hydroxyl group in the beta-position of the side chain decreased pA2 values. The slopes of the regression lines for anti-TMQ action of MES derivatives as well as PR were almost one, but those for their anti-ISO action were less than 0.3. 3,4,5-Trimethoxyaniline and 3,4,5-trimethoxybenzoic acid had little activity as beta-blocking agents. These results suggest the possibility that TMQ and ISO would interact with the same receptor sites. The importance of the trimethoxybenzene and the phenethylamine moieties in the MES-derivatives for anti-TMQ action is discussed.

Adrenergic beta-Agonists↗
PubMedDate not supplied

Effect of diltiazem on calcium- and noradrenaline-induced contractions in isolated rabbit aorta.

The effect of diltiazem on calcium- and noradrenaline-induced contractions was investigated in the K-depolarized aortic strip of the rabbit. Diltiazem inhibited the contraction induced by calcium ions dose-dependently. A lower concentration of diltiazem produced no significant influence on the contraction induced by noradrenaline, while a higher concentration suppressed it. It is assumed that in the rabbit aorta diltiazem effectively inhibits the contraction mediated by the influx of calcium ions but it is less effective with the contraction induced by the release of sequestered calcium.

Animals↗