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Biomedical subjects

Y Kasuya

Publications and source records attributed to Y Kasuya.

At least 361 records · Page 20Linked to original sources

Effects of nonspecific smooth muscle relaxants on tissue concentrations of high energy phosphates and mechanical activity of normal polarized and depolarized intestinal smooth muscles from guinea pig.

Effects of nonspecific smooth muscle relaxants, an uncoupler and removal of Ca ions from physiological solution on the tissue concentrations of high energy phosphates, such as ATP and creatine phosphate (CP) and tension of the normal polarized and KCl-depolarized intestinal smooth muscles of guinea pig were studied. Decrease of CP-concentration induced by dinitrophenol (DNP; 10(-4) M) was accompanied by relaxation of the normal polarized and KCl-depolarized smooth muscles. DNP slightly (but significantly) decreased ATP-concentration in the normal polarized and KCl-depolarized smooth muscles. Application of papaverine ( 3 x 10(-5) M) relaxed the normal polarized taenia immediately but increased CP-concentration at 5 and 10 min and decreased the concentration at 20 min. When the depolarized smooth muscle was considerably relaxed by papaverine (3 x 10(10-5) M), there was little influence on the CP-concentration. After relaxation of the depolarized taenia as induced by papaverine had reached a maximal amplitude, CP-concentration decreased significantly. ATP-concentration was little influenced by papaverine in the normal polarized and KCl-depolarized muscles. Although the treatments with a synthetic antispasmodic drug, Aspaminol (3 x 10(-4) M), which was found to inhibit Ca-uptake by the intestinal smooth muscles, a Ca-blocker, D-600 (10(-6) M) and removal of Ca ions from physiological solution relaxed the polarized and depolarized smooth muscles, the tissue concentrations of CP and ATP increased. These phenomena are considered to be due to decrease of the intracellular Ca-concentration.

Adenosine Triphosphate↗

Selective abolition of Ca-dependent responses of smooth and cardiac muscles by flunarizine.

The inhibitory effect of flunarizine on the Ca-dependent responses was compared with that of verapamil in isolated smooth and cardiac muscles. Flunarizine at a small dose shifted to the right the dose-response curve for Ca2+ of the phasic contraction due to electric stimuli in rabbit basilar strips, while in a large dose, flunarizine reduced the maximum tension and slope of the dose-response curve. The high K+-induced vasoconstriction of the rabbit basilar artery was inhibited by flunarizine. However, the action of flunarizine was about 30 times slower than findings with verapamil. The spontaneous activity of the rat portal vein was less susceptible to flunarizine, whereas that of rat uterus was completely inhibited by flunarizine. Flunarizine possessed moderate negative chronotropic and inotropic actions on the right atria and papillary muscles of the rabbit. Our experiments indicate that flunarizine is selective in antagonizing Ca-dependent contraction of the rabbit basilar artery, probably by blockade of the transmembrane Ca. It is also possible that the slow onset of action and nonsurmountable antagonism produced by flunarizine is due to other pharmacological interventions such as delayed effect of metabolites, stabilizing action or tight binding on the cell membrane of vascular smooth muscles.

Animals↗

Enhancement by elevated external potassium of the maximal responses to acetylcholine and norepinephrine in the rat vas deferens.

In the rat vas deferens, the maximal response to acetylcholine increased almost linearly as a function of external potassium concentration, [K+]0. The magnitudes of the maximal responses in 10, 15 and 20 mM [K+]0 were 128, 155 and 184% of the maximal response in 6 mM [K+]0, respectively. The response to carbachol also increased in 20 mM [K+]0 to almost the same extent. The enhancement of the norepinephrine response was observed only in 20 mM [K+]0; its magnitude was only 125%. The increase in [K+]0 from 6 to 20 mM did not affect the sensitivity (expressed as the geometric mean ED50) either to norepinephrine or to acetylcholine. Denervation of the postganglionic nerves to the vas deferens did not affect the enhancement of the maximal responses in 20 mM [K+]0, indicating that the release of neuronal transmitters may not be involved.

Acetylcholine↗

Determination of plasma testosterone by mass fragmentography using testosterone-19-d3 as an internal standard. Comparison with radioimmunoassay.

Analytical procedures for the measurement of testosterone by mass fragmentography (MF) using trideuterated testosterone (testosterone-19,19,19-d3) are described. For the calculation of plasma testosterone, peak height ratios were measured by MF performed on the molecular ions of the TFA derivative of testosterone (m/e 480) and testosterone-19,19,19-d3 (m/e 483). The sensitivity of the method was judged from the lower limit of detection of the mass spectrometer which was at 10 pg. For the measurement of the precision, the inter- and intra-assay coefficients of variation (C.V.) were calculated by using a pooled plasma sample; they were 3.15% and 1.79%, respectively. The specificity was investigated by the use of 5 alpha-dihydrotestosterone and the MF method was found to afford a highly selective technique. These results obtained by MF have been compared with the results obtained by a radioimmunoassay method.

Gas Chromatography-Mass Spectrometry↗

Rhythmic contractions induced by vagotomy in the fundus of rat stomach.

Continuous rhythmic contractions were observed in longitudinal muscle strips of fundus obtained from the chronically vagotomized rat stomach. These vagotomy-induced rhythmic contractions (VRC) were not blocked either by tetrodotoxin (3 x 10(-6) M) or atropine (3 x 10(-7) M), indicating that the VRC was myogenic in origin. It was also found that the VRC had the following characteristics. 1) The VRC blocked either by 10(-5) M D600 or by Ca2+ deprivation from the medium. 2) On replacement of Na+ with sucrose or of K+ with Na+, the tone of fundus strips was concomitantly elevated with the cessation of the VRC. 3) 10(-5) M ouabain blocked the VRC. 4) The VRC was blocked by cooling. 5) The VRC disappeared under anoxic conditions. Based on these results possible mechanisms of the VRC are discussed in relation to an energy dependent activity of the cell membrane.

Animals↗

Inhibitory alpha-adrenergic action of phenylephrine in guinea pig taenia caecum.

Phenylephrine, a selective alpha-adrenergic stimulant, caused a maximal relaxation of the taenia from guinea pig caecum in the concentration of 10(-6) g/ml. Phenylephrine in this concentration did not influence intracellular cyclic AMP and cyclic GMP levels. Although phenylephrine abolished the spontaneous spike discharge, no change was detected in 45Ca-uptake and 45Ca-efflux on the tissue level after phenylephrine. Ca-uptake and Ca-release on the subcellular level were also not influenced by phenylephrine. In Ca free-solution phenylephrine inhibited the response to CaCl2. Phenylephrine increased 42K-efflux in the normally polarized taenia and also in the K-depolarized taenia.

Action Potentials↗

Effects of smooth muscle stimulants on 1-isoprenaline-beta-adrenoceptor interaction in taenia from guinea pig caecum.

An increase in intracellular cyclic AMP levels induced by 1-isoprenaline (1-Iso) was significantly depressed in coexistence with BuTMA or histamine, but not with KCl or BaCl2. An analysis of steady state data for d,1-[3H]-isoprenaline binding to single cells of taenia from guinea pig caecum in the presence of histamine or KCl by Scatchard plots was performed. The affinity for 1-Iso for beta-adrenoceptor sites was decreased in the presence of histamine but not in the presence of KCl. These results suggest that the interaction of 1-Iso with the beta-adrenoceptors is interfered with by histamine and butyltrimethylammonium, for which the specific receptors were postulated, but not with KCl and BaCl2, nonspecific smooth muscle stimulants. These phenomena demonstrate the heterotropic negative cooperatively among the heterogeneous receptors.

Animals↗

The mechanism of aggravation of indomethacin-induced gastric ulcers by adrenalectomy in the rat.

Bilateral adrenalectomy markedly aggravated gastric ulcers in rats induced by 5 or 20 mg/kg of indomethacin. The degree of aggravation was much the same in experiments done 1 and 14 days after operation. Pretreatment with prednisolone 10 mg/kg or cortisone acetate 10 mg/kg given subcutaneously significantly suppressed the aggravated ulceration in response to 20 mg/kg of indomethacin in these adrenalectomized rats. Desoxycorticosterone acetate 10 mg/kg, however, had no effect on the aggravation of indomethacin-induced ulcers. Epinephrine 0.1 or 1 mg/kg given subcutaneously markedly suppressed the indomethacin-induced ulcers in adrenalectomized rats. Removal of the adrenal medulla alone did not appreciably influence the development of indomethacin-induced ulcers. These results indicate that the adrenal cortex, particularly the area containing glucocorticoids, plays an important role in suppression of the noxious effect of indomethacin on the rat gastric mucosa.

Adrenal Glands↗

Denervation-like supersensitivity in the rat vas deferens induced by local application of colchicine to the hypogastric plexus.

In an attempt to induce denervation-like supersensitivity in the smooth muscle of the vas deferens without depriving the tissue of its innervation, a small amount of colchicine was locally applied to the hypogastric plexus of the rat. Colchicine produced supersensitivity and a partial depletion of the tissue norepinephrine. These effects were dose-dependent. The supersensitivity produced by colchicine was qualitatively and quantitatively similar to that induced by denervation. Following application of 20 micrograms of colchicine, the supersensitivity was fully developed by the 4th day. The supersensitivity began to decline by the 6th day but was measurable even after 16 days. Functional neuromuscular transmission was maintained even on the 4th day after colchicine application, although it was significantly less than the control. The time course of the development of supersensitivity was dependent on the length of the adrenergic nerve between the colchicine-applied site and the effector cells. The results indicate that supersensitivity is independent of an irreversible degeneration of the adrenergic nerves. The possible mechanisms of action of colchicine are discussed in relation to the known effects of colchicine on axoplasmic transport.

Animals↗

Variation of postjunctional natures along the length of the rat vas deferens as a cause of regional difference in the sensitivity to norepinephrine.

Sensitivity to norepinephrine (expressed as pD2) was different between the prostatic and the epididymal half of the rat vas deferens. The epididymal half was more sensitive than the prostatic half; difference in pD2 was 0.826 +/- 0.095 (mean +/- S.E., 13 experiments). Between the two halves, nearly the same difference in pD2, 0.745 +/- 0.125 (6 experiments), was observed in the responses to methoxamine, which is not incorporated into the adrenergic nerve terminals. In the two halves, 3 x 10(-6) M phentolamine produced a smiliar decrease in pD2 of norepinephrine: 1.485 +/- 0.056 and 1.282 +/- 0.080 in the prostatic and epididymal half, respectively (6 experiments). Only in the prostatic half, 10(-5) M propranolol produced a slight increase in pD2 of norepinephrine, 0.344 +/- 0.133 (6 experiments). Sensitivity to K+ was also different between the two halves. These results suggest that the difference in the sensitivity to norepinephrine between the prostatic and the epididymal half is due to postjunctional natures varying along the length of the rat vas deferens.

Animals↗

A difference in effects of physiological Ca2+ concentrations on activity of guanylate cyclase preparations obtained from the taenia caecum of guinea pig and from the longitudinal muscle of rat duodenum.

A cholinergic stimulant, butyltrimethylammonium bromide and serotonin increased the tissue levels of cyclic GMP in the taenia caecum of guinea pig but not those in the longitudinal muscle of rat duodenum. On the other hand, physiological Ca2+ concentrations enhanced the activity of a guanylate cyclase preparation obtained from the taenia caecum of guinea pig, while guanylate cyclase in the longitudinal muscle of rat duodenum was not influenced by Ca2+. The difference in the effects of the smooth muscle stimulants on the tissue levels of cyclic GMP in two different smooth muscles in attributed to differences in the properties of guanylate cyclase of smooth muscles.

Animals↗