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Biomedical subjects

Y Kasuya

Publications and source records attributed to Y Kasuya.

At least 325 records · Page 18Linked to original sources
PubMed1983

Synthesis and antihypertensive activity of stereoisomers of 4-piperidyl-1,3-dihydro-2-oxo-2H-benzimidazoles. Enhanced potencies of (+) isomers.

To elucidate the relationship between the pharmacological activity and stereochemical structure, we resolved 1-[2-(3-,4,5-trimethoxyphenyl)-2-hydroxy-1-methylethyl]-4-(1,3-dihydro-2-oxo-2H -benzimidazol-1-yl)piperidine (1 and 2) and 1-[2-(3,4-dimethoxyphenyl)-2-hydroxy-1-methylethyl]-4-(1,3-dihydro-2-oxo-2H-benzimidazol-yl)piperidine (3), which produced hypotensive effects mainly through their alpha-blocking actions. Threo isomers 1 and 3 were resolved via diastereomeric carbamates. Erythro isomer 2 was obtained by an oxidation and reduction sequence from optically active 1. No significant difference was found between the pharmacological activities of the threo and erythro isomers of the corresponding compounds. However, a clear difference was found between the pharmacological activities of the optical isomers. Difference was most clearly shown in the hypotensive actions of normotensive rats and in alpha-adrenergic blocking activities of isolated rat vas deferens. In these actions, (+) isomers were always more potent than the corresponding (-) isomers.

Animals↗
PubMed1983

Studies on the hypotensive effects of platelet activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine) in rats, guinea pigs, rabbits, and dogs.

Platelet activating factor (PAF) showed profound and long-lasting hypotensive effects in normotensive and spontaneously hypertensive rats, guinea pigs, rabbits and dogs. Sensitivity to PAF was different among the animal species. The magnitude and duration of the hypotensive effect was dose-dependent. Pharmacological studies suggested that the hypotensive action was unlikely to be caused by the actions on the central or autonomic nervous systems but seemed to be mainly due to some direct action(s) on the peripheral blood vessels.

Animals↗
PubMed1983

The pharmacokinetics of insulin after continuous subcutaneous infusion or bolus subcutaneous injection in diabetic patients.

Pharmacokinetic models of insulin were examined in order to describe a plasma concentration-time profile after subcutaneous (s.c.) administration of insulin to the patients with insulin-dependent diabetes mellitus (IDDM) or non-insulin-dependent diabetes mellitus (NIDDM). Diabetic subjects were restricted to those with fasting plasma insulin levels around the lowest limit for insulin assay (5 microU/ml). A one-compartment open model with first-order absorption and elimination was appropriate for estimating the plasma concentration-time profile of insulin injected or infused subcutaneously. In the case of continuous s.c. insulin infusion (CSII) for 1 h at the rate of 3 ml/h (2--3 U/ml), the absorption rate constant (Ka), elimination rate constant (Ke), and distribution volume (Vd) were 0.026 +/- 0.001 min-1 (mean +/- SEM; absorption half-life: 27 min), 0.013 +/- 0.005 min-1 (elimination half-life: 53 min), and 1.99 +/- 0.49 L/kg body wt, respectively. These values did not differ significantly from those generated by single bolus s.c. injection of undiluted insulin (40 U/ml). The calculated areas under the plasma insulin concentration-time curves from time zero to infinity ([AUC] 0 infinity) did not differ after each mode of administration, while the [AUC] 0 infinity after CSII was about 32% of that following intravenous bolus injection (P less than 0.01). The following conclusions can be drawn from these results: (1) the plasma concentration-time profile of insulin after CSII or bolus s.c. injection can be analyzed by pharmacokinetic modeling, (2) the absorption kinetics of insulin did ot differ significantly between two modes of s.c. insulin administration in the patients with IDDM or NIDDM, and (3) the insulin after CSII or single bolus s.c. injection seems to be degraded at the s.c. site to the same extent.

Adult↗
PubMed1983

Hypotensive action of a new benzimidazolinone derivative, threo-1-(2-hydroxy-2-(3,4,5-trimethoxyphenyl)-1-methylethyl)-4-(1,3-dihydro-2H-benzimidazol-2-one-1-yl)piperidine (KF-4942): prazosin-like mode of action.

Among a series of benzimidazolinone derivatives, KF-4942 was examined on its mode of hypotensive action. It was found that KF-4942 was a potent hypotensive agent, and that the hypotension was produced mostly by alpha-adrenergic blockade. Alpha-adrenergic blocking action of KF-4942 was suggested to be selective to the postsynaptic receptor. Thus, KF-4942 was concluded to be an agent with properties similar to prazosin.

Adrenergic alpha-Antagonists↗
PubMed1982

The effect of denervation of the cyclic nucleotides levels of the vas deferens.

We measured the cyclic nucleotides in levels of the rat vas deferens surgically denervated in order to investigate the relationship between denervation supersensitivity and cyclic nucleotides. Two days after denervation, cyclic AMP slightly decreased to 90.4% of control and cyclic GMP also decreased but not significantly. So it is assumed that almost all of the cyclic nucleotides are not neurogenic but myogenic. When the rat vas deferens was incubated with l-norepinephrine 10(-4) for 3 min, the cyclic GMP level in the vas deferens denervated for seven d was significantly higher than that in the intact specimen, and the cyclic AMP level in the intact one was almost the same as in the denervated preparation. Denervation produced leftward shift of the dose response curve in cyclic GMP level to l-norepinephrine. After incubation with acetylcholine (10(-4)M), however, cyclic GMP and cyclic AMP levels in the denervated vas deferens were almost the same as in the intact one. Therefore, it is suggested that cyclic nucleotides don't relate to the induction of nonspecific supersensitivity by denervation in the rat vas deferens.

Acetylcholine↗
PubMed1982

Effect of various drugs and extrinsic denervation on the non-adrenergic inhibitory neurons in the rat stomach.

The effects of various drugs and extrinsic denervation on the non-adrenergic inhibitory nerves in the rat stomach were examined. Stimulation of the intramural nerves supplying the longitudinal smooth muscle strips taken from the rat stomach produced responses consisting initial contractions followed by relaxations in the presence of guanethidine in case of the tone of the preparation maintained with serotonin. After scopolamine treatment, transmural nerve stimulation (TMS) caused a relaxation or a relaxation followed by a transient after-contraction. All of these responses were abolished reversibly with tetrodotoxin. After cold storage of rat stomach strips for 5 d at 4 degrees C, the TMS-induced response was not observed, but noradrenaline still relaxed these strips. The TMS-induced relaxation reached a maximum amplitude at 2-5 Hz, and was entirely independent of alpha- and beta-blockers, or a combination of them. It was not affected by treatment of 6-hydroxydopamine and reserpine. These results strongly suggested that the relaxation was not myogenic, but neurogenic, and was not elicited by stimulation of adrenergic neurons. Strychnine and poly-L-lysine inhibited the relaxation elicited by TMS even in normal and transection-treated rats. Histochemical studies showed degenerative changes due to the dissection at the axons of a ganglion in the Auerbach's plexuses by transection. The effect of various drugs and extrinsic denervation on the response to TMS in relation to non-adrenergic inhibitory nerves in the rat stomach is discussed.

Adenosine Triphosphate↗
PubMed1982

A comparative study of changes in innervation and development of supersensitivity in the rat vas deferens after various procedures.

The relationship between morphological and functional changes in adrenergic nerves and the development of supersensitivity in the rat vas deferens was comparatively investigated after surgical denervation, chemical sympathectomy by 6-hydroxydopamine, daily treatment of animals with reserpine, or local application of colchicine to the hypogastric plexus. The order of ability to produce supersensitivity, as judged by the extent of the increase in the pD2 value of norepinephrine and the maximum response to norepinephrine, was as follows: denervation = colchicine greater than 6-hydroxydopamine greater than reserpine. These procedures produced alterations in morphological characteristics of the nerve ending with severeness of degeneration in the following order: denervation greater than 6-hydroxydopamine greater than colchicine greater than reserpine. Twitch contractions induced by transmural nerve stimulation were slightly reduced after colchicine or 6-hydroxydopamine treatment, markedly reduced by reserpine, and abolished by denervation. Therefore, the development of supersensitivity in the rat vas deferens is not necessarily in proportion to the morphological or functioning changes in adrenergic nerves. The results suggest that some neurofactor, e.g. trophic factor, is involved in the control of the drug sensitivity of smooth muscle in addition to the neurotransmitter itself.

Animals↗
PubMed1982

A new device for the determination of microsomal cytochrome P-450 in renal tissue preparations from various species contaminated with mitochondria and hemoglobin.

Using a spectrophotometer connected to a microcomputer, the carbon monoxide difference spectrum of renal microsomal dithionite-reduced cytochrome P-450 was measured avoiding the effects of the contaminating mitochondrial cytochromes and hemoglobin by subtracting the CO difference spectrum of a succinate-treated microsomal suspension from that of a dithionite-treated one. By this method, we quantitatively determined the microsomal cytochrome P-450 in kidneys from various species. The absorption peak of the renal microsomal cytochrome P-450 was about 452 nm in rats and about 450 nm in mice, hamsters, rabbits, guinea pigs, dogs, and pigs. Compared with the renal cytochrome P-450 contents in rats, the contents on a g tissue basis were greater in pigs, dogs, and mice and were about the same in hamsters and rabbits. The renal cytochrome P-450 contents in guinea pigs were less than those in rats.

Animals↗
PubMed1982

Postjunctional supersensitivity in young rat heart produced by immunological and chemical sympathectomy.

Postnatal changes in sensitivity to norepinephrine (NE) were studied in normal and sympathectomized rat hearts. The sensitivity of left atria to NE was highest at birth, after which it declined, reaching the adult level by 2 weeks of age. Developmental changes in NE sensitivity of the left atria seemed to be related to the density of sympathetic innervation, and the high sensitivity at birth was most likely due to the lack or immaturity of the uptake function of the nerve endings. In contrast to the atria, right ventricular papillary muscle did not change in NE sensitivity with age. Immunological and chemical sympathectomy was performed by repetitive administration of antiserum to nerve growth factor and 6-hydroxydopamine, respectively. Both atria and papillary muscles from immunologically and chemically sympathectomized rats were supersensitive to NE at all ages tested. Inasmuch as the supersensitivity to NE was most marked at the 4th week of age, atria of this age were used for the study on the mechanisms of supersensitivity. Left atria from sympathectomized 4-week-old animals were also supersensitive to isoproterenol and phenylephrine. Because isoproterenol and phenylephrine are not taken up into sympathetic nerve endings, it was concluded that the postjunctional mechanisms were involved in the genesis of the denervation supersensitivity of left atria.

Animals↗
PubMed1981

Effects of hypoxia and metabolic inhibitors on the electrical and mechanical activities of isolated guinea pig papillary muscles.

Electrical and mechanical activities of the isolated guinea pig papillary muscle were measured simultaneously, and the effects of various degrees of hypoxia and metabolic inhibitors were examined. Hypoxia selectively diminished the action potential duration (APD) dependently upon the degree of hypoxia with little affecting the other parameters of the action potential. Hypoxia concomitantly depressed the contractile force (CF), but the decrease in CF always preceded the decrease in APD; thus, the complete excitation-contraction uncoupling was sometimes observed. Metabolic inhibitors (dinitrophenol, DNP and monoiodoacetic acid, IAA) produced qualitatively the same changes in the electrical and mechanical activities. However, DNP mimicked hypoxia better than IAA which produced rather parallel decreases in CF and APD. The slow response action potential (elicited after inactivation of the excitatory fast Na system of the membrane) was completely blocked by hypoxia and metabolic inhibitors, which was partially restored by isoproterenol, histamine and tetraethylammonium. When isoproterenol was present in the bathing solution, the decreases in CF and APD produced by hypoxia were accelerated, but ATP and propranolol did not significantly modify the hypoxically induced changes.

2,4-Dinitrophenol↗
PubMed1981

Effects of cocaine on Ca-mobility in microsomal fraction from rat vas deferens.

Cocaine (3 x 10(-5) M) has been reported to potentiate maximal contraction induced by several stimulants, and this phenomenon might be ascribed to the postsynaptic action. The present study was undertaken to observe the influences of cocaine on Ca-movements, that is, Ca-uptake and Ca-release, in the microsomal fraction of the prostatic half of the rat vas deferens. In this study, it was shown that cocaine potentiated Ca-uptake at the lower concentration (10(-6) M) of Ca2+, but had no influence upon Ca-release and also that cocaine significantly increased the rate of Ca-uptake. These results suggest that cocaine promotes binding of Ca ions with the surface sites of smooth muscle membrane concerned with Ca-influx process and thereby potentiates maximal contractions elicited by different stimulants.

Animals↗