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Y Akaishi

Publications and source records attributed to Y Akaishi.

At least 19 recordsLinked to original sources
PubMed2001

Role of endothelial Ni(2+)-sensitive Ca(2+) entry pathway in regulation of EDHF in porcine coronary artery.

Elevation of intracellular Ca(2+) concentration ([Ca(2+)](i)) in endothelial cells is proposed to be required for generation of vascular actions of endothelium-derived hyperpolarizing factor (EDHF). This study was designed to determine the endothelial Ca(2+) source that is important in development of EDHF-mediated vascular actions. In porcine coronary artery precontracted with U-46619, bradykinin (BK) and cyclopiazonic acid (CPA) caused endothelium-dependent relaxations in the presence of N(G)-nitro-L-arginine (L-NNA). The L-NNA-resistant relaxant responses were inhibited by high K(+), indicating an involvement of EDHF. In the presence of Ni(2+), which inhibits Ca(2+) influx through nonselective cation channels, the BK-induced EDHF relaxant response was greatly diminished and the CPA-induced response was abolished. BK and CPA elicited membrane hyperpolarization of smooth muscle cells of porcine coronary artery. Ni(2+) suppressed the hyperpolarizing responses in a manner analogous to removal of extracellular Ca(2+). EDHF-mediated relaxations and hyperpolarizations evoked by BK and CPA in porcine coronary artery showed a temporal correlation with the increases in [Ca(2+)](i) in porcine aortic endothelial cells. The extracellular Ca(2+)-dependent rises in [Ca(2+)](i) in endothelial cells stimulated with BK and CPA were completely blocked by Ni(2+). These results suggest that Ca(2+) influx into endothelial cells through nonselective cation channels plays a crucial role in the regulation of EDHF.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2000

Coherent lambda-sigma coupling in s-shell hypernuclei

It is found that the suppression due to two-body LambdaN-SigmaN coupling solves the overbinding problem in (5)(Lambda)He but it, in turn, causes a severe underbinding in the four-body systems. The shortage of this binding is overcome by introducing explicitly the Lambda-Sigma coupling which is equivalent to the LambdaNN three-body force. This three-body force becomes strong in the 0(+) states of (4)(Lambda)H and (4)(Lambda)He according to the coherently added enhancement. The 0(+)-1(+) splitting in (4)(Lambda)H and (4)(Lambda)He is found partly due to the LambdaN spin-spin interaction and partly due to the Lambda-Sigma coupling in the recent Nijmegen soft-core potential.

Journal Article↗
PubMed2000

Involvement of tyrosine phosphorylation in the positive inotropic effect produced by H(1)-receptors with histamine in guinea-pig left atrium.

We investigated the effect of stimulation of H(1)-receptors with histamine on protein tyrosine phosphorylation levels in guinea-pig left atrium and evaluated the influences of tyrosine kinase inhibitors on the positive inotropic effect mediated by H(1)-receptors in this tissue. Histamine induced an increase in tyrosine phosphorylation in four main clusters of proteins with apparent molecular weights of 25, 35, 65 and 150 kDa. Tyrosine phosphorylation of these proteins attained a peak around 2 - 3 min following histamine stimulation and then declined to or below basal levels. Histamine-induced protein tyrosine phosphorylation was antagonized by the H(1)-receptor antagonists mepyramine (1 microM) and chlorpheniramine (1 microM), but not by the H(2)-receptor antagonist cimetidine (10 microM). The positive inotropic effect of histamine was depressed in a concentration-dependent manner by the tyrosine kinase inhibitors tyrphostin A25 (50 to 100 microM) and genistein (10 to 50 microM) but not by the inactive genistein analogue daidzein (50 microM). The positive inotropic effect of isoprenaline was unchanged by tyrphostin A25 and genistein. At a concentration of 1 microM histamine produced a dual-component positive inotropic response composed of an initial increasing phase and a second and late developing, greater positive inotropic phase. Treatment with tyrphostin A25 (100 microM) and genistein (50 microM), but not daidzein (50 microM), significantly attenuated the two components of the inotropic response, although genistein suppressed the initial component more markedly than the late component. We conclude that increased protein tyrosine phosphorylation may play an important role in initiating at least some part of the positive inotropic effect of H(1)-receptor stimulation in guinea-pig left atrium.

Animals↗
PubMed2000

Impairment of cardiac beta-adrenoceptor cellular signaling by decreased expression of G(s alpha) in septic rabbits.

BACKGROUND: Abnormalities in the beta-adrenergic control of cardiac function play a role in the pathogenesis of several disease states. Because circulatory failure in patients with septic shock is known to be less responsive to catecholamines, we investigated whether the beta-adrenoceptor-linked signal transduction mechanisms are altered in the heart of a septic animal model METHODS: Rabbits were rendered endotoxemic by an intravenous injection of 100 microg/kg Escherichia coli lipopolysaccharide. Three and 6 h later, the myocardial tissues were used for the experiments. RESULTS: The positive inotropic response to isoproterenol was significantly impaired in papillary muscles isolated from septic rabbits compared with those from controls. The impaired inotropic responsiveness to isoproterenol was not prevented by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine, indicating no involvement of nitric oxide overproduction. Adenylate cyclase activity stimulated with isoproterenol and 5'-guanylyl imidodiphosphate was markedly reduced in septic myocardium. The contractile and adenylate cyclase responses to colforsin daropate, a direct adenylate cyclase activator, were unaffected by sepsis. Radioligand binding experiments with (-)[125I]iodocyanopindolol revealed no significant alteration in myocardial beta-adrenoceptor density or affinity in sepsis. Determination of cardiac G(s alpha) level by Western blotting showed a reduction of approximately 50% in sepsis. The relative content of G(s alpha) messenger RNA in septic myocardium also was reduced from the control level by about 50%, as determined by Northern blot analysis. Little change was found in protein and messenger RNA levels of G(s alpha) in septic myocardium. CONCLUSIONS: Impairment of myocardial functional responsiveness to beta-adrenoceptor stimulation appears in the early stage of sepsis. The impaired response to beta-adrenoceptor stimulation in the heart in this pathologic state may result in part from a decreased level of G(s alpha) protein which occurs at the level of gene expression.

Adenylyl Cyclases↗
PubMed1999

Diabetes-induced down-regulation of beta1-adrenoceptor mRNA expression in rat heart.

The present study addressed the question of whether the number of myocardial beta-adrenoceptors in rats with 4- to 6-week streptozotocin-induced diabetes is regulated in a transcriptional or translational manner. Radioligand binding experiments with [3H]CGP 12177 {4-(3-t-butylamino-2-hydroxypropoxy)-[5,7-3H]benzimidazol-2-one} showed that the density of beta-adrenoceptors fell by 50% with no change in affinity in diabetic rat ventricular myocardium compared with age-matched control myocardium. The relative content of beta1-adrenoceptor mRNA in diabetic myocardium also was reduced from the control level by 57%, as determined by northern blot analysis. The reductions in myocardial beta-adrenoceptor number and beta1-adrenoceptor mRNA observed in diabetes were prevented by insulin therapy. These data indicate that the diminished density of myocardial beta-adrenoceptors in diabetes occurred, at least in part, at the mRNA level.

Animals↗
PubMed1997

Agonist-independent tonic inhibitory influence of Gi on adenylate cyclase activity in rabbit ventricular myocardium and its removal by pertussis toxin: a role of empty receptor-mediated Gi activation.

We evaluated whether Gi has a tonic inhibitory influence on myocardial adenylate cyclase (AC) in an agonist-independent way, and, if so, whether this is attributable to substantial coupling between agonist-free, empty inhibitory receptors and G. Rabbits received pertussis toxin (PTX, 10 micrograms/kg i.v.) 40 h before preparing ventricular myocardial membranes, which was associated with virtually complete in vivo ADP-ribosylation and inactivation of the 41-kDa substrate. Pretreatment with PTX had no influence on basal AC activity but significantly enhanced AC activity elicited by 100 microM GTP. Furthermore, it markedly increased AC activity stimulated with 5'-guanylyl imidodiphosphate (GppNHp) and isoproterenol through a wide range of concentrations of these stimulants. These findings indicate that Gi has a tonic influence on he stimulatory effects of guanine nucleotides and beta-adrenoceptor stimulation on AC even in the absence of the inhibitory receptor agonists. The muscarinic receptor antagonists atropine and AF-DX 116 significantly enhanced isoproterenol-stimulated AC activity, as PTX pretreatment did, except that statistically significant increasing effects of these antagonists on GppNHp-stimulated AC activity was observed only at higher concentrations of GppNHp. The enhancement by atropine was not detected in PTX-pretreated membranes. The selective beta 2-adrenoceptor antagonist ICI 118,551 did not modify the stimulatory effects of guanine nucleotides and isoproterenol on AC in either control or PTX-pretreated membranes, excluding the possible involvement of beta 2-adrenoceptors in tonic activation of Gi. We conclude that Gi is tonically activated by agonist-free, empty muscarinic receptors, which leads to attenuation of Gs-mediated or beta-adrenoceptor-mediated activation of AC. The potentiating effect of PTX pretreatment on GppNHp-stimulated AC activity may be at least partially due to the direct action of PTX on the Gi heterotrimeric complex, independently of the coupled receptors.

Adenosine Diphosphate↗
PubMed1997

Impaired contractile response to beta adrenoceptor stimulation in diabetic rat hearts: alterations in beta adrenoceptors-G protein-adenylate cyclase system and phospholamban phosphorylation.

The aim of this study was to explore the cellular mechanisms underlying the impaired contractile response to beta adrenoceptor stimulation in diabetic hearts. Chronic diabetes was induced in rats by a streptozotocin injection. Four to six weeks later, papillary muscles isolated from diabetic hearts exhibited marked reductions in the positive inotropic responses to isoproterenol, norepinephrine and epinephrine. The contractile responses to forskolin, 3-isobutyl-1-methylxanthine and dibutylic cyclic AMP were also prominently depressed. The density of beta adrenoceptors was decreased by 50%. However, competitive binding studies with isoproterenol showed no difference in the proportion of beta adrenoceptors with high-affinity binding between control and diabetic myocardial membranes. Determination of the levels of the alpha subunits of Gs and Gi by immunoblotting revealed markedly less expression of Gi in diabetic myocardium. The abilities of isoproterenol, sodium fluoride, 5'-guanylyl imidodiphosphate and forskolin to stimulate adenylate cyclase were preserved well in membranes prepared from diabetic hearts. Nevertheless, neither stimulation of beta adrenoceptors with isoproterenol nor direct activation of adenylate cyclase with forskolin evoked any significant increase in the degree of phosphorylation of phospholamban in diabetic hearts. These results suggest that impaired contractile response to beta adrenoceptor stimulation is not caused by an alteration in the beta adrenoceptors-Gs-adenylate cyclase system, but is possibly caused by an alteration in cellular function beyond the step of adenylate cyclase activation.

1-Methyl-3-isobutylxanthine↗
PubMed1996

Alpha 1-adrenoceptor subtypes mediating inotropic and electrophysiological effects in mammalian myocardium.

Stimulation of alpha 1-adrenoceptors produces a positive inotropic effect in rat and rabbit ventricular myocardium via different mechanisms, the prolongation of action potential duration (APD) exclusively in the former and an increase in myofibrillar Ca2+ sensitivity in large part in the latter. This study was designed to determine whether the two inotropic mechanisms are mediated by different alpha 1-adrenoceptor subtypes. In rat papillary muscles, the positive inotropic effect and APD prolongation induced by phenylephrine (in the presence of propranolol) were inhibited by WB-4101, but not affected by chlorethylclonidine (CEC). WB-4101, but not CEC, blocked the phenylephrine-induced inhibition of the transient outward current (Ito) in rat ventricular cells. On the other hand, WB-4101 and CEC each antagonized the positive inotropic effect of phenylephrine in rabbit papillary muscles. However, the phenylephrine-induced APD prolongation observed in rabbit papillary muscles was blocked only by WB-4101. These results indicate that the WB-4101 sensitive alpha 1-adrenoceptor subtype mediates the positive inotropism that is correlated with the APD prolongation resulting from Ito reduction, whereas the CEC-sensitive subtype mediates the positive inotropism that is probably associated with increased myofibrillar Ca2+ sensitivity. Radioligand binding studies with [3H] prazosin showed a similar ratio of alpha 1A-to alpha 1B-adrenoceptor subtypes in rat and rabbit ventricular myocardium, implying that the different degree of contribution of each action mechanism to the overall inotropic effect in the two species cannot be explained by distribution of the alpha 1-adrenoceptor subtypes.

Adrenergic alpha-Agonists↗
PubMed1996

Alpha 1-adrenoceptor subtype distribution and the coupling to phosphoinositide hydrolysis in rat and rabbit ventricular myocardium.

The relative contributions of the alpha 1A- and alpha 1B-adrenoceptor subtypes to the stimulation of phosphoinositide (PI) hydrolysis in rat and rabbit ventricular myocardium were defined pharmacologically using WB-4101 and chloroethylclonidine (CEC). Radioligand binding experiments with [3H]prazosin showed that the maximum number of alpha 1A-adrenoceptors in rat myocardium was about ten times higher than in rabbit myocardium. The proportion of the two [3H]prazosin binding sites with high and low affinity for WB-4101 was similar in the two species: approximately 30% of the alpha 1-adrenoceptor population was pharmacologically alpha 1A and approximately 70% was alpha 1B. Phenylephrine produced concentration-dependent stimulation of PI hydrolysis in rat ventricular strips as measured by [3H]inositol monophosphate accumulation, but this stimulation was much less in rabbit. In both of the two species, WB-4101 was very effective in inhibiting phenylephrine-stimulated PI hydrolysis, whereas CEC had a minimal effect. Altogether, the degree of PI hydrolysis appears to be determined by the density of myocardial alpha 1-adrenoceptors. However, despite the greater density of the alpha 1B-subtype, it is the alpha 1A-subtype that is mainly coupled to PI hydrolysis in mammalian myocardium.

Adrenergic alpha-Agonists↗
PubMed1995

A morphological study of the retinal ganglion cells of the Afghan pika (Ochotona rufescens).

The distribution and morphology of the retinal ganglion cells was studied in a relative of the rabbit, the Afghan pika. The total number of retinal ganglion cells was approximately 170,000. The total number of optic nerve fibers was between 160,000 and 190,000, corresponding to the total number of retinal ganglion cells. Retinal ganglion cells were found to have a horizontal region of high-density. The maximum density was 5250 cells/mm2. This region was located in the central retina below the optic disc. This area contained numerous closely packed small ganglion cells, while the peripheral retina (especially in the dorsal periphery) contained large ganglion cells more loosely dispersed. The retinal ganglion cells labeled by horseradish peroxidase (HRP) were morphologically classified into three types based on dendritic length and ramification pattern.

Animals↗
PubMed1995

Inotropic changes induced by fluoroaluminates in rabbit left atrial muscles: possible involvement of G proteins.

1. The effects of fluoroaluminate complexes (NaF plus AlCl3) on force of contraction, cyclic AMP accumulation and phosphoinositide hydrolysis were examined in rabbit left atrial muscles. 2. Fluoroaluminates (1-10 mM NaF + 10 microM AlCl3) produced a biphasic inotropic response which was composed of an early small decline and subsequent increase in force of contraction. In the presence of the Al3+ chelator, deferoxamine (100 microM), the positive inotropic response was completely abolished and a sustained negative inotropic response appeared, suggesting that only the positive inotropic response is due to the action of fluoroaluminates. 3. The positive inotropic effect of fluoroaluminates was associated with a significant increase in the total duration of a single contraction; the time to peak tension and relaxation time were prolonged. In contrast, these parameters were substantially abbreviated by isoprenaline or histamine. 4. When force of contraction was increased by isoprenaline or histamine, the addition of fluoroaluminates caused a marked negative inotropic effect, which was eliminated by pretreatment with pertussis toxin. 5. Fluoroaluminates did not cause a significant increase in cyclic AMP content at concentrations of NaF in the range of 1-10 mM. However, the content of cyclic AMP was greatly elevated by fluoroaluminates when the atrial muscles were pretreated with pertussis toxin. 6. Accumulation of [3H]-inositol monophosphate in atrial muscle strips prelabelled with myo-[3H]-inositol was significantly increased by fluoroaluminates at concentrations of NaF over 1 mM. The phosphoinositide response to fluoroaluminates remained unchanged with pertussis toxin pretreatment. 7.These results indicate that, in rabbit left atrial muscles, fluoroaluminates produce a positive inotropic effect which may be mediated by Gq but not by Gs proteins; they produce a negative inotropic effect possibly through Gi only when Gs is activated with other agents.

Aluminum↗
PubMed1994

Pertussis toxin pretreatment alters agonist binding to beta-adrenoceptors in rabbit ventricular myocardium.

The influence of pretreatment with pertussis toxin (PTX) on characteristics of beta-adrenoceptor bindings was examined in myocardial ventricular membranes prepared from rabbits which received an intravenous injection of PTX (10 micrograms/kg) or its vehicle. The density and affinity of beta-adrenoceptors assessed by (-)-[125I]iodocyanopindolol were not significantly altered by PTX pretreatment. However, a fraction of agonist binding sites with high affinity significantly increased in PTX-pretreated myocardial membranes. In the presence of 100 microM 5'-guanylyl imidodiphosphate, all agonist binding sites were converted to low-affinity sites in both control and PTX-pretreated membranes. The results suggest that Gi might regulate negatively coupling of beta-adrenoceptors to Gs.

Animals↗
PubMed1993

[Effects of intravenous injection of ioversol, a nonionic contrast medium, on circulating blood volume: comparison among different combinations of its dose and volume injected].

Effects on circulating blood volume (CBV) of the intravenous injection of a nonionic contrast medium, ioversol, with various doses were assessed in order to find a way of injection with less effects on systemic circulation. Ioversol was injected as a bolus to 20 mongrel dogs at doses of A: 3.75 ml/kg (n = 8) or B: 2 ml/kg (n = 6) of a solution containing 320 mg iodine per ml, or C: 2 ml/kg (n = 6) of a 240 mgI/ml solution. Colloid oncotic pressure (COP) of the bloods drawn before and 1, 2, 3, 5 min after the injection of ioversol was measured by a needle type osmometer, and changes in CBV were calculated using the COP values. Upon injection of ioversol CBV increased rapidly and then gradually returned to the preinjection levels. The change in CBV induced by ioversol was significantly less than those reportedly induced by an ionic contrant medium, iothalamate, and a nonionic medium, iopamidol, and comparable to that by another nonionic medium, iohexol. The degree of increase in CBV and the blood concentration of ioversol were related to the amount, but not the volume, of ioversol injected. Thus, ioversol proved to be one of the low osmotic nonionic contrast media with less effects on CBV. Furthermore, it is suggested that the amount, rather than volume, of contrast medium should be taken into consideration when the angiography of the patients with reduced cardiac function, children or aged patients is performed in whom the contrast medium-induced CBV expansion needs to be as less as possible.

Animals↗
PubMed1990

Dipyridamole potentiates the anti-aggregating effect of endothelium-derived relaxing factor.

One effector of the anti-aggregatory property of endothelium is thought to be endothelium-derived relaxing factor. The best characterized of these, nitric oxide, inhibits platelet aggregation by increasing cyclic GMP levels. The effects of nitric oxide and dipyridamole (a cyclic GMP phosphodiesterase inhibitor), alone and in combination, on in vitro platelet aggregation were evaluated. Dipyridamole had no effect per se on platelet aggregation but potentiated the inhibition of aggregation due to nitric oxide. This was concomitant with an increase in platelet cyclic GMP concentration. The author suggests an alternative mechanism for the clinical efficacy of dipyridamole as an antiplatelet agent.

Cyclic AMP↗