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Biomedical subjects

K Tamura

Publications and source records attributed to K Tamura.

At least 991 records · Page 55Linked to original sources
PubMed1990

General pharmacological profiles of the new beta-adrenoceptor antagonist carvedilol.

General pharmacological properties of carvedilol (BM 14.190) were investigated in comparison with propranolol. 1. Central nervous system: Carvedilol caused reduction of awareness, motor activity and muscle tone, and staggering gait in Irwin's test (mice). It decreased spontaneous motor activity and potentiated hexobarbital anesthesia (mice). It lacked anticonvulsant activity (mice) and did not have any effect on body temperature (rabbits). Various changes were produced in mono- and polysynaptic spinal reflex (cats). In EEG, a slight arousal pattern was observed (cats). These effects of carvedilol were weaker than those observed after propranolol administration in general. Carvedilol, however, caused potentiation of hexobarbital anesthesia at lower doses than propranolol. Carvedilol inhibited acetic acid-induced writhing syndrome, whereas it failed to show analgesic activity in the tail-pinch test (mice). Propranolol inhibited both pain reactions. 2. Respiratory and cardiovascular system (dogs): Carvedilol increased respiratory rate and decreased expiratory velocity. It produced hypotension and bradycardia. Cardiac contractility was reduced and femoral blood flow was transiently increased after carvedilol administration. Propranolol induced weaker hypotension and greater bradycardia in comparison with carvedilol. It decreased femoral blood flow. 3. Autonomic nervous system: Carvedilol had little or no effects on pupil size, whereas propranolol produced mydriasis (rabbits). Carvedilol inhibited pressor response to norepinephrine (rats), and it also reduced the nictitating membrane contraction induced by pre- and postganglionic sympathetic nerve stimulation (cats). Propranolol did not show any inhibitory effect on pressor response to norepinephrine and on the contractile response induced by preganglionic sympathetic nerve stimulation. 4. Smooth muscle: Carvedilol produced inhibitory effects on spontaneous motility, and contractile responses to acetylcholine, histamine, nicotine, serotonin and BaCl2 in isolated ileum (guinea pigs). It also inhibited contractile responses to acetylcholine and histamine in isolated trachea (guinea pigs), and spontaneous motility in isolated uterus (rats). Carvedilol reduced norepinephrine-induced contraction of isolated vas deferens at lower concentration (guinea pigs). 5. Digestive system: Decrease in intestinal motility was observed after intravenous administration of carvedilol and propranolol (rabbits). However, carvedilol failed to influence on gastric motility and tonus, whereas propranolol increased them (rabbits). Carvedilol, like propranolol, induced little or no effects on gastro-intestinal transit (mice) and gastric emptying rate (rats). Both drugs decreased gastric secretion at similar dose (rats). Carvedilol at higher doses produced lesion of gastric mucosa, whereas propranolol did not show these effects (rats). 6. Skeletal muscle: In in vitro experiment, carvedilol, like propranolol, reduced the contractile response of diaphragm to nerve and muscle stimulation (rats)...

Adrenergic beta-Antagonists↗
PubMed1990

Two pharmacologically distinct alpha 1-adrenoceptor subtypes in the contraction of rabbit aorta: each subtype couples with a different Ca2+ signalling mechanism and plays a different physiological role.

Using the alpha 1-adrenoceptor subtype-selective antagonists chlorethylclonidine (CEC), WB4101, and 5-methyl-urapidil, we have examined the possible heterogeneity in the alpha 1-adrenoceptor populations in rabbit aorta. The alpha 1-adrenoceptor alkylating agent CEC selectively inhibited the phasic component of the norepinephrine-induced contractile response, with little effect on the tonic component. The alpha 1-adrenoceptor occupancy-response relationship defined by the phenoxybenzamine inactivation method was rectangular hyperbolic for the tonic response, whereas that for the phasic response was linear, indicating the different degree of receptor reserve for the two responses. Radioligand binding studies with the nonselective alpha 1-adrenoceptor antagonist radioligand 125I-BE2254 showed that 73-87% of the binding sites in rabbit aorta are CEC sensitive and they are predominantly low affinity sites both for WB4101 (pKd = 8.1) and for 5-methylurapidil (pKd = 7.1). Moreover, alpha 1-adrenoceptor-mediated phosphatidylinositol (PI) hydrolysis was CEC sensitive, and fractional inactivation of alpha 1 receptors with CEC showed equivalent increments in the reduction of PI hydrolysis and phasic contractile response, suggesting that both responses are linearly related to the CEC-sensitive receptor sites. The Schild plots for the competitive antagonists WB4101 and 5-methyl-urapidil against alpha 1a-adrenoceptor-selective agonist methoxamine-induced contraction were linear and had slopes not significantly different from unity, with a pA2 of 9.07 +/- 0.07 (n = 5) for WB4101 and 9.09 +/- 0.05 (n = 3) for 5-methyl-urapidil. However, the Schilod plots for these antagonists against norepinephrine were curvilinear. Computer-assisted analysis of these curvilinear Schild plots in a two-receptor system indicated that alpha 1-adrenoceptor populations responsible for the constrictive response are predominantly (approximately 80-90%) low affinity sites for the two antagonists (pKd approximately 8.1 for WB4101 and pKd approximately 7.1 for 5-methyl-urapidil) and a small population (approximately 10-20%) are high affinity sites (pKd approximately 9.1 for both WB4101 and 5-methyl-urapidil), which was in good agreement with radioligand binding studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1990

A transfected m5 muscarinic acetylcholine receptor stimulates phospholipase A2 by inducing both calcium influx and activation of protein kinase C.

Receptor-mediated arachidonic acid release and its relationship to phospholipase A2 and phospholipase C activation were investigated in Chinese hamster ovary cells transfected with and expressing the m5 muscarinic receptor. Carbachol, a muscarinic receptor agonist, stimulated the release of arachidonic acid and inositol phosphates with similar potencies. In addition, carbachol and the phorbol ester, phorbol-12-myristate, 13-acetate (PMA), stimulated protein kinase C (PKC) activity. PMA potentiated the carbachol-stimulated release of arachidonic acid, but had no effect on release of inositol phosphates. Long-term preincubation with PMA or carbachol inhibited PKC activity and prevented carbachol-stimulated release of arachidonic acid, but not inositol phosphates, suggesting that release of arachidonic acid, but not release of inositol phosphates, required activation of PKC. Carbachol stimulated the release of [3H]lysophosphatidylcholine from [3H]choline prelabeled cells, suggesting that phospholipase A2 was involved in the release of arachidonic acid. The role of calcium in carbachol-stimulated release of arachidonic acid was also investigated. Carbachol stimulated a transient followed by a sustained increase in intracellular calcium. In the absence of extracellular calcium, the transient rise in intracellular calcium was maintained but the sustained increase in intracellular calcium and the release of arachidonic acid were abolished. Carbachol stimulated a sustained influx of 45Ca++. We conclude that the combined effect of PKC activation and sustained elevation of intracellular calcium, from an extracellular source, is essential for m5 muscarinic receptor activation of phospholipase A2.

Animals↗
PubMed1990

[Organ specific ESR features in mouse main organs and ESR application to the model of pancreatic disorders].

Nine main organs in the mouse were studied by ESR spectroscopy at 77K. Manganese ions were readily detected in the pancreas, small intestine, stomach and kidney. In particular, the pancreas gave strong ESR signals for the transition metal, suggesting that Mn(II) plays an important role in pancreatic function. All organs reveal different ESR spectra indicating organ specificity. C-centered radical, R-OO radical and C0Q10 or ascorbate radical are stable in the tissue. In the brain, heart and pancreas, N-centered radical heme-NO adduct was detected at 6 and 24 h after excision since common process is involved in tissue degeneration and ESR is sensitive to proteolysis and necrosis of tissues. In endotoxemia and/or CDE-diet-induced pancreatic lesions, R-OO radical and Mn(II) ion were detected in the signal at 77K. By the spin-trapping method (DMPO) at 25 degrees C, DMPO-OH adduct and 3-Line and 6-Line were detected in CDE diet-induced acute pancreatitis. These results suggest that damaged pancreatic tissues are in a highly oxidative environment that probably contains oxygen radicals, and that free radicals are considered to play an important role in the development of pancreatic lesions.

Animals↗
PubMed1990

[A case of malignant aortico-pulmonary paraganglioma].

A 64-year-old male was admitted to our hospital suffering from dysphagia and dyspnea. The chest X-ray films and chest CT films revealed huge tumor in his upper-anterior mediastinum. The filling defect at lower rim of the left brachiocephalic vein on venography indicated malignant potential of the tumor. There was no abnormal value in blood and urine examinations except CA 19-9 which was 31.8 U/ml. The tumor was resected with bilateral pleura, pericardium and left brachiocephalic vein. Macroscopically the specimen accompanied with a lot of bleeding spots was soft and yellow and has no capsule. The size of tumor was 15 X 13 X 8 cm and its weight was 865 gm. No tumor recurrence was found until present time: two years after surgical therapy followed by adjuvant radiation therapy (60 Gray). Though histological findings of anterior part of the tumor were consisted of "Zellballen" cells and bleedings, the posterior part had cell atypia and invasion into vessels. These cells were slightly positive on Keratin stain and on NSE stain. Typical findings of paraganglioma were also indicated by electron microscopy: those findings were more chief cells, fewer sustentacular cells, abundant mitochondria and few dense-cored granules which are thought to secrete hormonal substances. Judging from these clinical and pathological results, this tumor was diagnosed nonfunctional aortico-pulmonary paraganglioma. Mediastinal paraganglioma is a very rare tumor. There is no report of malignant aortico-pulmonary paraganglioma in Japan after Glenner and Grimelys' study concerning extra-adrenal paraganglion system.

Aorta↗
PubMed1990

[Inflammatory reaction and laboratory tests: IAP (immunosuppressive acidic protein)].

The immunosuppressive acidic protein (IAP), a type of alpha 1-acid glycoprotein has been used as to monitor cancer and inflammation in patients, though it lacks disease specificity. We studied the serum IAP values in 41 patients with renal cell carcinoma. The normal upper limit of serum IAP concentration is 500 micrograms/ml, and a higher value was determined as positive. Serum IAP values and its positive ratios as determined by Robson stage analysis were respectively, 495 + 118 micrograms/ml and 35% (6/17), 757 + 333 micrograms/ml and 90% (9/10), and 921 + 277 micrograms/ml and 100% (14/14), at low (1 + 2) stage, stage 3, and stage 4, respectively. We also studied serum IAP values of the 41 patients above according to Satomi's classification. The positive ratio as 100% (14/14) for the quick type, and 67% (18/27) for the slow type. In addition, we studied the serial serum IAP values in these patients. The serum IAP values decreased to or were within the normal range by one month after operation in 10 patients with curative nephrectomy, while in 8 patients with non-curative nephrectomy abnormally high levels of serum IAP were seen one month after operation except in one case. The serum IAP value was considered as a useful factor in determining the prognosis of patients with renal cell carcinoma.

Biomarkers, Tumor↗
PubMed1990

[Experimental study on liver accumulation of N-isopropyl-p-iodoamphetamine].

In order to clarify the mechanism of N-isopropyl-p-iodoamphetamine (IMP) liver accumulations, liver dynamic study by the portal injection of 123I-IMP and liver microautoradiography by 125I-IMP were performed using 5, 2 male rats, respectively. The initial uptake of 123I-IMP in the liver was very high and thereafter 123I-IMP showed relatively rapid wash-out (count ratio of lung to liver at 10 min after the injection was 0.12, 0.15). On the other hand, the addition of 5 mg, 8 mg ketamine hydrochloride decreased the initial 123I-IMP liver uptake and its lung accumulation was noted immediately after the injection (count ratio of lung to liver at 10 min was 0.20). Microautoradiography of the liver using 125I-IMP showed grain density in the central vein and sinusoids, but not in the liver parenchymal cell. These results suggest that non-specific amine receptor (binding site) may exist in the endothelial cell in the central vein, although the number of experimental rats in this series was small for conclusion.

Amphetamines↗