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Biomedical subjects

T Yanagisawa

Publications and source records attributed to T Yanagisawa.

At least 19 recordsLinked to original sources
PubMed1992

Role of acetylcholinesterase in airway epithelium-mediated inhibition of acetylcholine-induced contraction of guinea-pig isolated trachea.

To seek evidence for the involvement of acetylcholinesterase activity in the modulatory influence of the airway epithelium, we examined responses to acetylcholine (ACh), bethanechol, histamine or KCl in isolated epithelium-intact and epithelium-denuded guinea-pig trachealis preparations. The concentration-response curves to ACh were shifted 26-fold to the left by epithelial denudation but the contractile response to KCl was not altered. The response to histamine in epithelium-denuded preparations increased 4-fold with no attenuation in the presence of physostigmine (30 nM). Physostigmine (30 nM) potentiated the response to ACh in epithelium-intact tissues more (about 26-fold) than in epithelium-denuded tissues (about 3.5-fold). Thus, in the presence of physostigmine removing the epithelium had only a slight effect (not statistically significant) on the potency of ACh to contract the trachea. Removing the epithelium had no effect on the potency of bethanechol, a muscarinic receptor agonist that is not a substrate for cholinesterases. Physostigmine itself contracted the trachealis muscle but the pD2 values and maximum responses in epithelium-intact and denuded preparations were not significantly different. The frequency-response curves to electrical field-stimulated cholinergic contractions were unaffected by removing the epithelium. In conclusion, the principal mechanism by which the epithelium inhibits contraction of guinea-pig trachea to exogenously applied ACh is via epithelium-derived acetylcholinesterase activity.

Acetylcholine↗
PubMed1992

E4080 has a dual action, as a K+ channel opener and a Ca2+ channel blocker, in canine coronary artery smooth muscle.

To clarify the vasodilating mechanism of action of E4080, which possesses vasodilating and bradycardic effects, we investigated its effects on intracellular Ca2+ concentrations ([Ca2+]i), as measured with fura-2, and force of contraction in canine coronary artery. E4080 reduced the increase in [Ca2+]i and force of contraction induced by 30 and 90 mM KCl physiological salt solution (PSS) in a concentration-dependent manner. The effects of E4080 in 30 mM KCl-PSS were inhibited by 10(-5) M glibenclamide. In 30 mM KCl-PSS, the slope of the [Ca2+]i-force relationship in the presence of E4080 was steeper than that of control, suggesting that E4080 decreased the sensitivity of contractile elements to Ca2+, as an effect which was also inhibited by glibenclamide. However, the [Ca2+]i-force curve was not changed by E4080 in 90 mM KCl-PSS. These results suggest that E4080 is a vasodilator in canine coronary artery, having K+ channel opening and Ca2+ channel blocking actions. The membrane hyperpolarization induced by E4080 may reduce the sensitivity of contractile elements to Ca2+.

Analysis of Variance↗
PubMed1992

Mechanisms involved in the pituitary desensitization induced by gonadotropin-releasing hormone agonists.

OBJECTIVE: We investigated the mechanisms of desensitization induced by gonadotropin-releasing hormone agonist in the pituitary. STUDY DESIGN: Effects of gonadotropin-releasing hormone agonist on the pituitary were studied in vitro and in vivo in the rat. In the clinical study serum luteinizing hormone was measured by radioimmunoassay with a polyclonal luteinizing hormone antibody (luteinizing hormone-radioimmunoassay) and by immunoradiometric assay with monoclonal luteinizing hormone antibodies (luteinizing hormone-immunoradiometric assay) during gonadotropin-releasing hormone agonist treatment. RESULTS: In the in vitro study bead-attached pituitary cells that were desensitized with a continuous infusion of 10(-7)mol/L gonadotropin-releasing hormone responded to 50 mmol/L K+. In the in vivo study gonadotropin-releasing hormone binding sites and rat luteinizing hormone beta-messenger ribonucleic acid in the pituitary decreased during gonadotropin-releasing hormone agonist treatment, but serum levels of rat luteinizing hormone did not decrease. In addition, a disparity between luteinizing hormone-radioimmunoassay and luteinizing hormone-immunoradiometric assay was demonstrated during gonadotropin-releasing hormone agonist treatment. CONCLUSION: Pituitary desensitization in response to gonadotropin-releasing hormone agonist may not be wholly receptor mediated and a nonreceptor process may be involved.

Animals↗
PubMed1992

[The role of beta-adrenoceptor subtypes in cardiac contractility].

Since the existence of beta 3-adrenoceptors in various organs has been established, it is necessary to re-evaluate the subtypes of beta-adrenoceptors in cardiac muscle. We have demonstrated the possible existence of three subtypes of beta-adrenoceptors: beta 2-adrenoceptors, high-affinity beta 1-adrenoceptors (the so-called beta 1-adrenoceptors) and the low-affinity beta 1-adrenoceptors (akin to beta 3-adrenoceptors) in canine cardiac muscle, which are coupled with increases in myocardial cyclic AMP content and positive inotropic effects. Cyclic AMP generated by the activation of the high-affinity beta 1-adrenoceptors seems to be coupled with the positive inotropic effect much more effectively than via beta 2- or low-affinity beta 1-adrenoceptors. Stimulation of beta 2-adrenoceptors or the low affinity beta 1-adrenoceptor is causally related to the development of tolerance and to the adverse effects of nonselective beta-full agonists. It is conceivable that with denopamine, unlike with isoproterenol, tolerance can hardly develop, and there are no adverse effects resulting from its partial agonistic property and its selectivity for the high-affinity beta 1-adrenoceptors. The selective stimulation of the high-affinity beta 1-adrenoceptors would be beneficial for the management of mild congestive heart failure. In contrast, stimulation of the low-affinity beta 1-adrenoceptors by endogenous catecholamines or nonselective beta-agonists will contribute to deteriorating hemodynamic, symptomatic and prognostic consequences in patients with congestive heart failure.

Adrenergic beta-Agonists↗
PubMed1992

KCl-depolarization potentiates the Ca2+ sensitization by endothelin-1 in canine coronary artery.

In Ca(2+)-free solution containing endothelin-1 (ET-1), depolarization by high KCl increased the force of contraction without any changes in intracellular calcium concentration ([Ca2+]i) in canine coronary artery. The [Ca2+]i-force relationships were examined in the absence or presence of ET-1 in 5 or 90 mM KCl. The relation curve in the presence of ET-1 in 90 mM KCl-PSS was shifted to the left and upward compared with that in 5 mM KCl. These results suggest that KCl-depolarization potentiates the Ca2+ sensitization by ET-1.

Animals↗
PubMed1992

Presence of multinucleate cells in the papillary layer of the Macaca fuscata enamel organ.

The enamel organ of Macaca fuscata from post-secretory transition to the early maturation stage of was investigated by means of light and electron microscopy. Unusual, large multinucleated cells were observed in the papillary layer. These cells contained organelles characteristic of the maturation stage ameloblast and often extended to the enamel surface, suggesting a possible origin from the ameloblast layer.

Ameloblasts↗
PubMed1979

Acid phosphatase activity demonstrated by intact Angiostrongylus cantonesis with special reference to its function.

Intact Angiostrongylus cantonensis is able to hydrolyse glucose-phosphate esters, mononucleotides and rho-nitrophenyl phosphate as well as beta-glycerophosphate in vitro. Reciprocal inhibition studies suggest that the hydrolysis of such substrates is due to a non-specific phosphomonoesterase. Molybdate ions, which exert no effect on either the uptake of glucose or the production of lactate, inhibit the hydrolysis of glucose-1-phosphate in the external medium and simultaneously lower the production of lactate by the intact worms in vitro.

Acid Phosphatase↗
PubMed1979

Circumstantial evidence for increased potassium conductance of membrane of cardiac muscle by 2-nicotinamidoethyl nitrate (SG-75).

The mechanism of action of 2-nicotinamidoethyl nitrate (SG-75), was investigated by the use of arterially blood-perfused papillary muscle preparations of the dog. All drugs were administered intra-arterially. SG-75 shortened the effective refractory period (ERP) and decreased the rate of automaticity and developed tension of the papillary muscle, whereas verapamil failed to change the ERP despite a decrease in the developed tension. SG-75 in extremely high doses induced ventricular fibrillation. Methacholine produced decreases in the rate of automaticity and developed tension, and the actions were abolished by atropine. The SG-75-induced decreases in two parameters were not modified by atropine. These results indicate that the cardiac action of SG-75 differs from that of calcium-antagonistic vasodilators and it is suggested that the basic mechanism of action of SG-75 involves an increase in potassium conductance in the membrane of cardiac muscle, without mediation through muscarinic receptors.

Animals↗
PubMed1979

Comparative studies on actins from various sources. Fragments of actins from Ascaris muscle cleaved at cysteinyl residues in comparison with those of other actins.

Pure actins were obtained from various animal muscles: Vertebrata (skeletal, smooth, and cardiac muscles), Prochordata (smooth muscle), Nematoda (obliquely striated muscle), and Mollusca (striated, smooth and obliquely striated muscles). These actins were all identical in apparent molecular weight on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. All actins treated with 2-nitro-5-thiocyanobenzoic acid yielded four major (about 33,000, 26,000, 24,000, and less than 10,000 daltons) and three minor (22,000, 17,000, and 10,000 daltons) bands in addition to intact actin on gel electrophoresis. The results suggest that all actins from various types of muscle have cysteinyl residues at similar positions on the primary structure.

Actins↗
PubMed1979

Simultaneous assessment of the effects of trimetazidine on the myocardium and coronary vasculature of the dog.

The effects of trimetazidine on the electrical and mechanical activities of the myocardium were investigated in comparison with the effect on the coronary blood flow in blood-perfused preparations excised from dog hearts. In the sinoatrial (SA) node preparation trimetazidine injected into the sinus node artery increased blood flow and depressed SA node automaticity. In the atrioventricular (AV) node preparation trimetazidine injected into the AV node artery or the anterior septal artery increased blood flow and equally prolonged AV conduction time. In the papillary muscle preparation trimetazidine injected into the anterior septal artery increased blood flow and depressed force of contraction. These cardiodepressant actions occurred in the same range of doses of trimetazidine that exerted the vasodilator action. This indicates that trimetazidine has no selective activity on the coronary vasculature alone. Moreover, the vasodilator effect was more short-lived than the cardiodepressant action. Trimetazidine injected into the anterior septal artery affected ventricular bipolar electrograms. This, taken together with the prolongation of AV conduction time obtained with the same route of administration, suggests that the cardiodepressant action of trimetazidine is ascribed to the local anaesthetic or the membrane stabilizing action rather than to the calcium-antagonistic action.

Animals↗
PubMed1978

Excitation of autonomic nerves by 4-aminopyridine in the isolated, blood-perfused sino-atrial node preparation of the dog.

4-Aminopyridine injected into the sinus node artery produced a long-lasting decrease in sinus rate preceded by a transient increase. With a large dose, a long-lasting increase in sinus rate was superimposed on the long-lasting decrease phase. The long-lasting decrease and increase in sinus rate were abolished by 1-hyoscyamine and propranolol respectively, and both were reduced by tetrodotoxin. These results can be interpreted as being due to excitation of autonomic nerves by 4-aminopyridine.

Animals↗
PubMed1978

Effects of calcium-antagonistic coronary vasodilators, nifedipine and verapamil, on ventricular automaticity of the dog.

In isolated, blood-perfused canine papillary muscles intra-arterial injection of calcium-antagonistic coronary vasodilators, nifedipine and verapamil, produced a dose-related decrease in force of contraction. The ventricular rate of about 40 beats/min was not significantly changed by nifedipine even in doses which profoundly decreased the force of contraction. Verapamil changed the ventricular rate in a biphasic manner, but the changes remained as small as about 10% of the basal rate in doses which markedly suppressed the force of contraction. Calcium chloride elicited an increase in force of contraction but depressed automaticity. The present results show that in response to nifedipine, verapamil and calcium ions, ventricular automaticity has characteristics different from those of the sinus node.

Animals↗
PubMed1978

Characterization of adrenoceptors mediating positive inotropic responses in the ventricular myocardium of the dog.

1 The pharmacological characteristics of adrenoceptors mediating the positive inotropic action in the dog heart were assessed by the use of blood-perfused papillary muscles and isolated strips of ventricular myocardium.2 On the blood-perfused papillary muscle driven at 2 Hz and in sinus node preparations, phenylephrine induced positive inotropic and chronotropic responses in the same dose range and was much less potent than isoprenaline. The dose-response curve for the chronotropic action of phenylephrine was parallel to that of isoprenaline, whilst the dose-response curve for the inotropic action of phenylephrine was less steep than that of isoprenaline.3 The infusion of pindolol, a beta-adrenoceptor blocking agent, at a rate of 1 mug/min, shifted the isoprenaline dose-response curves to the right, and to the same extent, in both papillary muscle and sinus node preparations. In contrast to isoprenaline, the antagonism of phenylephrine by pindolol was noncompetitive. Phentolamine did not affect the positive inotropic and chronotropic actions of phenylephrine.4 On isolated ventricular strips alpha-adrenoceptor blockade by 10(-6) M phentolamine did not affect dose-response curves to phenylephrine or dopamine. Pindolol shifted the dopamine dose-response curves to the right in a competitive manner and those of phenylephrine in a noncompetitive manner.5 On ventricular strips from reserpine-pretreated dogs phenylephrine and tyramine dose-response curves were shifted markedly to the right and downwards. Desipramine (10(-5) M) which enhanced the action of noradrenaline considerably reduced the myocardial responses of phenylephrine.6 Papaverine (10(-5) M) decreased the threshold concentration of phenylephrine required to stimulate the myocardium and shifted phenylephrine dose-response curves to the left.7 Raising the temperature from 32 degrees C to 37 degrees C shifted phenylephrine dose-response curves to the right; when the temperature was raised from 37 degrees C to 42 degrees C the affinity of the drug was not changed.8 Other alpha-adrenoceptor stimulants, methoxamine and clonidine, decreased the active tension of ventricular strips. The responses to noradrenaline and adrenaline (in the presence of pindolol; 3 x 10(-8) M) were not affected by phentolamine (10(-6) M).9 The results indicate that adrenoceptors mediating positive inotropic responses in the dog ventricle are of the beta-type and that post-synaptic alpha-adrenoceptors are not involved. Phenylephrine acts mainly by releasing noradrenaline from adrenergic nerve endings and partly by a weak direct action on beta-adrenoceptors.

Adrenergic beta-Antagonists↗