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Biomedical subjects

Y Kasuya

Publications and source records attributed to Y Kasuya.

At least 253 records · Page 14Linked to original sources
PubMed1989

Inhibition of the vagal reflex-induced tracheal constriction by psychotropic drugs.

We investigated the effects of psychotropic drugs on reflex tracheal constriction in anesthetized, paralyzed, and artificially ventilated mongrel dogs. The tracheal constriction induced by the electrical stimulation of the central cut end of the right vagus nerve was abolished by sectioning both the left superior laryngeal and recurrent laryngeal nerves, and was reduced by a low dose of pentobarbital (3 mg/kg, i.v.). This indicates that the tracheal constriction is mediated by a vagal reflex. Chlorpromazine (3 mg/kg, i.v.) and imipramine (1-3 mg/kg) reduced the reflex tracheal constriction. Chlorpromazine and imipramine had no effect on the tracheal constriction induced by the efferent electrical stimulation of the recurrent laryngeal nerve. This suggests that the higher centers may affect the reflex airway constriction and that the present preparation may be useful for investigating the effect of psychotropic drugs on the reflex airway constriction during asthmatic attacks.

Airway Resistance↗
PubMed1989

Influence of carotid chemoreceptors on the vagal reflex-induced tracheal constriction.

In this study, the effects of carotid chemoreceptors on reflex tracheal constriction were investigated in anesthetized, paralyzed, and artificially ventilated mongrel dogs. Reflex tracheal constriction was measured as changes in the intratracheal pressure of an air-filled balloon introduced into the rostral side of the transected trachea. A hypoxic condition was produced by ventilating the dog with 12% O2-88% N2. The reflex tracheal constriction induced by histamine inhalation to the bronchial side was reduced by section of the bilateral sinus nerves. The hypoxic condition significantly potentiated the reflex tracheal constriction induced by histamine inhalation. The potentiated reflex tracheal constriction during hypoxia was abolished by section of the bilateral sinus nerves. The afferent electrical stimulation to the central cut end of the vagus nerve caused a reflex tracheal constriction. The reflex tracheal constriction was significantly potentiated by hypoxia, and the potentiating response was abolished by section of the bilateral sinus nerves. The infusion of NaCN into the bilateral carotid arteries significantly potentiated the reflex tracheal constriction. The NaCN-induced potentiating effect was abolished by section of the bilateral sinus nerves. These results suggest that hypoxia potentiates the vagal reflex-induced tracheal constriction and that the hypoxia-induced potentiating effects may be mediated by carotid chemoreceptors.

Administration, Inhalation↗
PubMed1989

Involvement of endothelial cells in relaxation and contraction responses of the aorta to isoproterenol in naive and streptozotocin-induced diabetic rats.

Experiments were designed to investigate the importance of the endothelium in the relaxation of isolated rat aorta caused by a beta adrenoceptor agonist. Mechanical removal of the endothelium attenuated the relaxation induced by isoproterenol (ISO) and did not affect the relaxation produced by forskolin and by sodium nitroprusside. High concentrations of ISO produced an increase in the resting tension of aortic strips with and without endothelium in a concentration-dependent manner. Mechanical removal of the endothelium or treatment with methylene blue enhanced the maximal contraction induced by ISO. Phentolamine antagonized the contractile responses induced by ISO. In the case of streptozotocin-induced diabetic rats, both aortic strips with and without endothelium generated concentration-response curves for ISO-induced relaxation that were shifted to the right. The relaxant responses to forskolin and sodium nitroprusside were not significantly different between vessels from diabetic and age-matched control rats. In both aortic strips with and without endothelium, the maximal contraction in response to high concentrations of ISO was significantly enhanced in strips from diabetic rats. These results suggest that ISO-induced relaxation of aortic strips with endothelium is mediated by beta adrenoceptors on both the endothelium and the smooth muscle, and high concentrations of ISO produce an increase in the resting tension through alpha adrenoceptors. It is further suggested that the decreased relaxant response of the aorta to ISO in diabetes may be due to decreased density or affinity of beta adrenoceptors on the smooth muscle.

Animals↗
PubMed1988

Structure-activity relationships of endothelin: importance of the C-terminal moiety.

The vasoconstrictor activities of various forms of derivatives of endothelin (ET) were characterized in vitro by measuring the contraction of porcine coronary artery strips. The removal of the C-terminal Trp21 reduced the molar potency of the peptide by nearly 3 orders of magnitude. The removal of amino acid residues from the C-terminus of ET(1-20) further attenuated the activity. Replacement of Trp21 with D-Trp, reduction and carboxamidomethylation of the four Cys residues, or cleavage at Lys9 by lysyl endopeptidase all lowered the potency approximately 200 fold. While both native ET and [D-Trp21]ET induced a very slow and sustained vasoconstriction, the other derivatives of ET listed above showed a much more rapid kinetics of vasoconstriction. These results indicate that the C-terminal Trp of ET is especially important for the potent and extremely long-lasting vasoconstrictor activity characteristic to ET.

Animals↗
PubMed1988

Supersensitivity of 5,7-dihydroxytryptamine-treated rats to the respiratory depressant and antitussive effects of dihydrocodeine.

The present study sought to determine whether rats, treated neonatally with 5,7-dihydroxytryptamine (5,7-DHT), have an increased sensitivity to the respiratory and cough-depressant effects induced by dihydrocodeine. The serotonin (5-HT) levels in the whole brain of 5,7-DHT-treated rats were reduced to 19% of the corresponding control values. The 5,7-DHT-treated rats were supersensitive to the depression in frequency of respiration and cough reflex produced by i.p. administration of dihydrocodeine. The increased sensitivity to dihydrocodeine in terms of the depression of frequency of respiration and the cough reflex in 5,7-DHT-treated rats could possibly have been due to changes in the sensitivity of serotonergic receptors.

5,7-Dihydroxytryptamine↗
PubMed1988

Determination of cortisol in human plasma by capillary gas chromatography-mass spectrometry using [2H5] cortisol as an internal standard.

A capillary gas chromatographic-mass spectrometric method for the determination of cortisol in human plasma using cortisol M + 5 as an internal standard is described. For calculation of plasma cortisol, peak areas were measured by selected-ion monitoring of the characteristic fragment ions of the dimethoxime-tri (trimethylsilyl) derivatives of cortisol and cortisol M + 5 (m/z 605 and 610, respectively). The inter- and intra-assay coefficients of variation for plasma sample were 3.07 and 1.77%, respectively. The method needed no complex corrections for contributions and provides a sensitive and reliable technique with good accuracy, precision and reproducibility.

Deuterium↗
PubMed1988

Determination of cortisol in human plasma by stable isotope dilution mass spectrometry.

Cortisol selectively labelled with 2H at the 19-methyl and the C-1 position (cortisol-d5) was synthesized and used as an internal standard in stable isotope dilution mass spectrometry in order to determine cortisol in human plasma. A capillary gas chromatographic/mass spectrometric method provided a sensitive and reliable technique with good accuracy, precision and reproducibility without complex corrections for contributions by using cortisol-d5 as an internal standard. For calculation of plasma cortisol, peak areas were measured by selected ion monitoring on the characteristic fragment ions of the dimethoxime tri(trimethylsilyl) derivatives of cortisol and cortisol-d5 (m/z 605 and 610, respectively). The sensitivity of the gas chromatographic/mass spectrometric assay was 1.02 ng per injection, with a signal-to-noise ratio of about 6. The inter- and intra-assay coefficients of variation for plasma sample were 3.07% and 1.77%, respectively.

Deuterium↗
PubMed1988

Stable isotope dilution mass spectrometry for the diagnostic study of histidinaemia.

Stable isotope dilution mass spectrometry for a diagnosis to detect the heterozygote state of histidinaemia has been developed. We have synthesized L-[3-15N, 5,beta,beta-2H3]histidine (histidine-[M + 4]) for use as a biological internal standard and DL-[1,3-15N2, 5,alpha,beta,beta-2H4]histidine (histidine-[M + 6]) as an analytical internal standard. For the gas chromatographic/mass spectrometric assay of stable isotopically substituted histidine in human plasma, histidine was derivatized to alpha N-trifluoroacetyl-imN-ethoxycarbonylhistidine n-butyl ester. Quantification was carried out by selected ion monitoring on the molecular ions (m/z 379, 383 and 385) of the respective gas chromatographic derivatives of non-labelled histidine, histidine-[M + 4] and histidine-[M + 6]. The calibration curve was linear over the range of 5-2000 ng ml-1 plasma (r = 0.9999). The intra- and inter-assay coefficients of variation were in the range 1.1-3.9%. The sensitivity, specificity, precision and accuracy of the method were demonstrated to be satisfactory for application to a pharmacokinetic study of histidine after administration of a trace amount of stable isotopically substituted histidine in man.

Amino Acid Metabolism, Inborn Errors↗
PubMed1988

Similarities between the relaxations induced by vasoactive intestinal peptide and by stimulation of the non-adrenergic non-cholinergic neurons in the rat stomach.

The characteristics of the non-adrenergic, non-cholinergic inhibitory response of the rat stomach fundus to transmural nerve stimulation were compared with the relaxation induced by vasoactive intestinal polypeptide (VIP). Treatment with alpha-chymotrypsin (5 U/ml) or VIP antiserum (1:200) significantly reduced the relaxation induced by transmural nerve stimulation at 30 Hz, indicating that the possible transmitter in the non-adrenergic, non-cholinergic nerves is a peptide and may be VIP or a closely related peptide. VIP was able to relax, fully and dose-dependently, the stomach fundus that had previously been constricted by treatment with 10(-6) M serotonin, and the IC50 value for VIP was 2.4 X 10(-9) M. VIP elevated levels of cyclic AMP in a dose-dependent manner and the EC50 value was 2.8 X 10(-9) M in the presence of 10(-6) M atropine and 10(-6) M guanethidine. The stomach fundus was relaxed by transmural nerve stimulation (30 Hz, 50 mA) and transmural nerve stimulation also caused production of cyclic AMP in the rat stomach in the presence of atropine and guanethidine. The basal level of cyclic AMP in the stomach was 8.7 +/- 0.26 pmole/mg protein. When transmural nerve stimulation was applied for 5 min, the contraction of the stomach, induced by 10(-6) M serotonin, was inhibited by 54% in the presence of atropine and guanethidine and the level of cyclic AMP was increased to 13.0 +/- 0.73 pmol/mg protein. Apamin inhibited the transmural nerve stimulation-induced relaxation and shifted the dose-response curve for VIP to the right.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Primary structure, synthesis, and biological activity of rat endothelin, an endothelium-derived vasoconstrictor peptide.

Endothelin is a potent vasoconstrictor/pressor peptide, which we recently characterized from the conditioned culture medium of porcine aortic endothelial cells. We report here the cloning and partial sequencing of the rat endothelin gene. The nucleotide sequence predicted a 21-residue peptide similar to, but distinct from, porcine endothelin; 15 residues of rat endothelin were identical and 3 residues were substitutions by chemically similar amino acid residues to those in the porcine peptide. Synthetic rat endothelin was then prepared according to its deduced amino acid sequence. This synthetic peptide had (i) potent vasoconstrictor activity in the rat aortic strip and in perfused rat heart and (ii) a characteristically long-lasting in vivo pressor activity by intraaortic bolus injection in the conscious rat.

Amino Acid Sequence↗
PubMed1988

Altered responsiveness to autonomic transmitters of hearts from neonatal spontaneously hypertensive rats.

Responsiveness to autonomic neurotransmitters of isolated hearts from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were compared in 1-day-old and 4-week-old neonates and adults. Chronotropic responses to norepinephrine (NE) and acetylcholine (Ach) were examined using right atrial preparations. There was no difference in the basal beating rate between SHR and WKY at all ages tested. The maximum beating rate produced by NE was higher in SHR only at 1 day after birth; there was no difference in the 4-week-old neonate and the adult. The sensitivity (pD2 values) to Ach was lower in SHR at both 1 day and 4 weeks after birth, but not in the adult. Inotropic responses to NE were examined using right ventricular preparations. The sensitivity was slightly higher in SHR at 1 day after birth, but no difference was observed in the 4-week-old neonate and the adult. These results suggested that the neonatal SHR heart has an increased function due to altered responsiveness to autonomic neurotransmitters, which may play a role in the initiation of hypertension.

Acetylcholine↗
PubMed1988

Organ culture of rat heart: maintained high sensitivity of fetal atria before innervation to norepinephrine.

Changes in sensitivity to norepinephrine (NE) of fetal and neonatal rat right atria placed in organ culture were examined. The high sensitivity to NE of the 17-day fetal atria was maintained during organ culture for 5 days. The pD2 value for NE at the 17th day of gestation was 8.66 +/- 0.09, and that after organ culture for 5 days was 8.62 +/- 0.09. The sensitivity of 1-day-old neonatal artia was significantly lower than that of fetal atria; but when they were cultured for 24 h, there was a 10-fold increase in sensitivity. The pD2 value before culture was 7.59 +/- 0.05, and that after culture was 8.54 +/- 0.04. NE added to the culture medium prevented this increase in sensitivity. Similar changes were observed in the sensitivity to isoproterenol, but not in the sensitivity to forskolin, indicating that these sensitivity changes were of a postjunctional nature and most likely due to some changes in the beta-receptor and (or) its coupling to adenylate cyclase. Therefore, the decrease in myocardial sensitivity to NE observed during the late fetal period is most likely to be caused by factor(s) related to sympathetic innervation.

Animals↗
PubMed1988

Changes in sensitivity of rat heart to norepinephrine and isoproterenol during pre- and postnatal development and its relation to sympathetic innervation.

Possible correlation between sympathetic innervation and sensitivity to adrenergic agonists was examined with developing rat hearts. Chronotropic responses of right atria to tyramine (TYR) was absent until the 15th day of gestation. After the 17th day of gestation, the maximum chronotropism by TYR was equal to that by norepinephrine (NE), indicating the development of functional sympathetic innervation to sinus node during this period. In ventricle, TYR responsiveness was low at birth and increased with age, indicating an increased sympathetic innervation during early postnatal period. Both in atria and ventricle, sensitivity to NE was high in early fetal ages followed by a 10-fold decrease after the onset of sympathetic innervation. Similar changes were observed in the sensitivity to isoproterenol, suggesting the postjunctional nature of this sensitivity change. There was no difference in sensitivities to dibutyryl cyclic AMP and forskolin between ventricles from 1-day- and 1-week-old neonates, suggesting changes in beta-receptor-adenylate cyclase system as a cause of this sensitivity change. The observed parallelism between functional sympathetic innervation and postjunctional sensitivity changes supports the hypothesis that sympathetic nerve exerts trophic influence upon cardiac muscle development to regulate the sensitivity to agonists.

Animals↗
PubMed1988

Kinetic analysis of the positive inotropic action (PIA) of ouabain in isolated perfused rabbit heart. Slow onset of PIA and slow binding to Na+, K+-adenosine triphosphatase.

The positive inotropic action (PIA) of ouabain was analyzed kinetically using isolated perfused rabbit heart. The input function of the ouabain concentration in the perfusate (Ci) into the heart was controlled by changing the volume of the reservoir and the rate of ouabain infusion into the reservoir fixed in front of the heart. The time courses of PIA were measured continuously with different infusion rates. The relationship between Ci and PIA clearly depended on the infusion rate in isolated perfused rabbit heart. The binding kinetics of ouabain to Na+, K+-adenosine triphosphatase (ATPase) in the cardiac homogenate showed two kinds of binding sites. The association rate constant (kappa 1), the dissociation rate constant (kappa-1) and the binding capacity of each site was estimated by the simultaneous fitting method. The occupation curve of the high affinity site corresponded well with the PIA measured in the isolated perfused heart at steady state. These results indicate that ouabain binding to the high affinity site is related to the PIA, and the slow binding process of ouabain to Na+, K+-ATPase may be one of the principal reasons for the infusion-rate dependence of ouabain PIA.

Animals↗
PubMed1988

Effects of double-enkephalin (biphalin), an enkephalin analogue, on respiration and the cough reflex in rats.

The pharmacological actions of double-enkephalin (biphalin; (HCl-Try-D-Ala-Gly-Phe-NH-)2) an analogue of enkephalin, on nociception, respiration and the cough reflex were compared with those of morphine in anesthetized rats. Double-enkephalin (D-Enk), injected i.p., produced significant analgesia at doses of 10 and 20 mg/kg in a hot-plate test. The analgesic effect of D-Enk was antagonized by pretreatment with naloxone (5 mg/kg, i.p.). D-Enk and morphine (M) produced a dose-dependent decrease in the frequency of respiration (RF) and in the tidal volume (Vt). However, the effects of D-Enk on RF and Vt were significantly weaker than those of M. The 50% antitussive dose (AtD50) of D-Enk and M were 0.63 and 0.48 mg/kg, i.p., respectively. The antitussive effect of D-Enk was antagonized by pretreatment with naloxone (0.4 mg/kg, i.p.). These results suggest that D-Enk exerted an antitussive effect similar to that of morphine, and that the involvement of opiate receptors is associated with the antitussive effect of D-Enk.

Analgesics↗
PubMed1988

Mechanisms of increased responses of the aorta to alpha-adrenoceptor agonists in streptozotocin-induced diabetic rats.

To investigate the influence of diabetes on the responsiveness of the cardiovascular system, we have examined the effects of various agents on the reactivity of the vascular smooth muscle of aortic strips obtained from age-matched control and diabetic rats. Norepinephrine (NE) contracted the aortic strips obtained from age-matched control and diabetic rats in a concentration-dependent manner, but maximal contraction of aortic strips in response to NE was enhanced in diabetic rats. The EC50 value for NE in the diabetic aortic strips was similar to that in the aorta from age-matched controls. Ca-induced contracture of the aortic strips which were depolarized with isotonic K+ (60 mM) was potentiated in aortic strips from diabetic rats, when compared with those from age-matched controls. Ca-induced contracture of aortic strips, preincubated with 10(-6) M NE and 10(-6) M nicardipine in Ca2+-free Krebs-Henseleit solution (KHS), was not significantly different in age-matched control and diabetic rats. Bay K 8644, an activator of calcium channels, produced an increase in the force of contraction of the slightly depolarized aorta from diabetic rats. Phasic contraction induced by phenylephrine (PE) in the presence of 10(-6) M nicardipine in Ca2+-free KHS was significantly enhanced in aortic strips obtained from diabetic rats. These results demonstrate that NE-induced contraction of the aortic strips obtained from diabetic rats was significantly enhanced, and that this increased contractile response of the aorta to NE may be due to an increased influx of extracellular calcium through the voltage-dependent Ca2+ channels, but not through the receptor-operated Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

Changes in sensitivity of the rat stomach fundus to various drugs in streptozotocin-induced diabetic rats.

The changes in sensitivity of the rat stomach fundus to acetylcholine (ACh), norepinephrine (NE), isoproterenol (ISO) and to vasoactive intestinal peptide (VIP) were examined in control rats and in streptozotocin (STZ)-induced diabetic rats. The dose-response curves for drugs were constructed 8 weeks after treatment with STZ. The dose-response curve for ACh in diabetic rats was shifted to the left as compared to the control curve, whereas the dose-response curves for NE, ISO and VIP were shifted to the right. These results suggest that functional changes in the autonomic nervous systems of the rat stomach fundus may occur in STZ-induced diabetic rats.

Acetylcholine↗