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Biomedical subjects

F Izumi

Publications and source records attributed to F Izumi.

At least 55 records · Page 3Linked to original sources
PubMed1996

Inhibitory effects of propofol on catecholamine secretion and uptake in cultured bovine adrenal medullary cells.

In the central and peripheral noradrenergic neurons, the balance between noradrenaline release and reuptake determines the level of noradrenaline at the synaptic cleft or the nerve ending. In the present study, we examined the effects of propofol, an intravenous general anaesthetic, on catecholamine secretion and noradrenaline uptake in cultured bovine adrenal medullary cells and on the serum noradrenaline and blood pressure in rats. In cultured adrenal medullary cells, propofol (10-50 mumol/l) concentration-dependently inhibited catecholamine secretion stimulated by carbachol. Propofol suppressed carbachol-evoked 22Na+ influx as well as 45Ca2+ influx at concentrations similar to those which suppressed the catecholamine secretion. Propofol (10-50 mumol/l) also inhibited veratridine-evoked 22Na+ influx, 45Ca2+ influx and catecholamine secretion, whereas it had little effect on the 45Ca2+ influx and catecholamine secretion induced by 56 mmol/l K+. Cultured adrenal medullary cells show [3H] noradrenaline uptake which is sensitive to imipramine. Propofol (10-50 mumol/l) significantly inhibited the imipramine-sensitive uptake of [3H] noradrenaline. In rats, intravenous administration of propofol (2.5 mg/kg) lowered serum noradrenaline and arterial blood pressure. From these findings, in spite of inhibiting noradrenaline uptake, propofol at anaesthetic concentrations (10-30 mumol/l) seems to reduce catecholamine secretion by interfering with Na+ influx through voltage-dependent Na+ channels as well as nicotinic acetylcholine receptor-associated ion channels in the adrenal medulla and, probably, in the sympathetic nervous system. This may explain the propofol-induced hypotension during anaesthesia.

Adrenal Medulla↗
PubMed1996

Proadrenomedullin N-terminal 20 peptide (PAMP) reduces inward currents and Ca2+ rises induced by nicotine in bovine adrenal medullary cells.

It has been recently reported that proadrenomedullin N-terminal 20 peptide (PAMP), which is secreted with adrenomedullin and catecholamines from the adrenal medulla, inhibits catecholamine release stimulated with nicotine. In the present study, to elucidate anticholinergic mechanisms of PAMP we employed the whole-cell patch-clamp and the intracellular Ca2+ imaging techniques in cultured bovine adrenal medullary cells. PAMP inhibited nicotinic currents and [Ca2+]i rises induced by nicotine in a dose-dependent manner (10(-9)-10(6) M). These inhibitions were selective, since PAMP alone did not induce any ionic currents, moreover it did not affect voltage-dependent Ba2+ currents or high K+ (50 mM)-induced [Ca2+]i rises. The onset of the inhibitory effect of PAMP (10(-6) M) was very rapid and reached a steady-state level within 10 sec. The effect of PAMP (10(-6) M) lasted for about 10-15 min. Desensitization process of the nicotinic current fitted to a single exponential function with a time constant of 6.4 +/- 0.3 sec. When PAMP (10(-6) M) simultaneously added with nicotine (10(-5) M), the desensitization process was facilitated and fitted to two exponentials with time constants of 0.46 +/- 0.08 and 2.5 +/- 0.8 sec. From the present results, the inhibition by PAMP of nicotinic currents which was well associated with that of nicotine induced [Ca2+]i rises leads to the attenuation of catecholamine release probably, at least in part, due to the facilitation of the desensitization process of the nicotinic currents.

Adrenal Medulla↗
PubMed1996

Ca(2+)/calmodulin-dependent protein kinase II inhibitor KN-62 inhibits adrenal medullary chromaffin cell functions independent of its action on the kinase.

KN-62, an inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II), inhibited significantly catecholamine secretion and tyrosine hydroxylase activity stimulated by acetylcholine in cultured bovine adrenal medullary cells. KN-62, however, showed an additional inhibitory effect on acetylcholine-induced 45Ca2+ influx, which is essential for functional responses. Carbachol-stimulated 22Na+ influx, veratridine-induced 22Na+ influx, and 56 mM K(+)-evoked 45Ca2+ influx were also attenuated by KN-62. Inhibitions by KN-62 of these ion influxes were correlated closely with those of catecholamine secretion. KN-04, which is a structural analogue of KN-62 but does not inhibit CaM kinase II activity, elicited inhibitory effects on the three kinds of stimulant-evoked ion influxes with an inhibitory potency similar to KN-62. These results suggest that KN-62 inhibits catecholamine secretion and tyrosine hydroxylase activation due to mainly its ion channel blockade on the plasma membrane rather than the inhibition of CaM kinase II activity in the cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1996

Inhibition by protamine of catecholamine secretion and ion influxes in bovine adrenal medullary cells in culture.

To elucidate the mechanism of protamine-induced hypotension, we examined the effects of protamine on catecholamine secretion in bovine adrenal medullary cells and on the serum norepinephrine in the rat. 1) in bovine adrenal medullary cells in culture, protamine at concentrations of 10 to 100 micrograms/ml inhibited catecholamine secretion stimulated by carbachol. The inhibitory effect of protamine was diminished by heparin at concentrations of 3.5 to 14 U/ml. Protamine suppressed carbachol-stimulated 22Na+ influx and 45Ca++2 influx at a concentration similar to that which inhibited catecholamine secretion. Protamine (10-100 micrograms/ml) also inhibited veratridine-induced 22Na+ influx and 45Ca++ influx and 56 mM K(+)-evoked 45Ca++ influx. The inhibition of these ion influxes by protamine was closely correlated with that of catecholamine secretion. 2) In rats, i.v. administration of protamine (10 mg/kg) attenuated the arterial blood pressure and the serum norepinephrine. There was a high correlation (r = 0.96) between the serum norepinephrine and the arterial blood pressure in protaminetreated rats. Furthermore, pretreatment with heparin (1000 U/kg) abolished the protamine-induced decreases in arterial blood pressure and serum norepinephrine. Because protamine seems to inhibit catecholamine secretion by interfering with Na+ influx and Ca++ influx to adrenal medullary cells, the protamine-induced hypotension may be, at least in part, due to inhibition of norepinephrine release and ion channel activities of sympathetic nerve terminals in rats.

Adrenal Medulla↗
PubMed1995

Effect of lidocaine on alpha 1-adrenoceptors in cultured neonatal rat cardiocytes.

The effect of lidocaine on alpha 1-adrenoceptors in cultured neonatal rat ventricular cardiocytes was studied by binding assay. When the cells were cultured in the presence of lidocaine, the binding of (+/-)-beta-([125I]iodo-4-hydroxyphenyl)-ethyl-aminomethyl-tetralone to the cells increased in a concentration- and time-dependent manner. The effect was due to an increase in maximum binding but not due to a change in the dissociation constant for the ligand. The increased number of alpha 1-adrenoceptors returned to the control level after culturing the cells without lidocaine. The stimulating effect on the number of alpha 1-adrenoceptors of lidocaine was also observed in the presence of norepinephrine. Other class I antiarrhythmic drugs such as procainamide. disopyramide, mexiletine and flecainide increased the number of alpha 1-adrenoceptors in the cells. These results suggest that cardiac responsiveness mediated by alpha 1-adrenoceptors is increased by class I antiarrhythmic drugs.

Adrenergic alpha-Antagonists↗
PubMed1995

Surgical excision of adrenal masses; a ten-year experience.

We reviewed the records of 13 patients with adrenal masses operated on over a ten-year period to clarify clinical characteristics of adrenal tumors. Tumors were found incidentally in seven of nine patients with primary adrenal tumors (78%); however, three of these seven patients (43%) proved to have shown symptoms related to adrenal hyperfunction when re-evaluated. Other adrenal tumors (metastatic in three patients and inflammatory in one) were found without any symptoms referable to the tumors. In nine of 13 patients (69%), tumors were discovered by computerized tomography (CT). All patients with primary tumors have been gotten free of disease postoperatively. In contrast, although all three patients with metastatic adrenal tumors underwent resection of all known disease tissue, they died of the recurrence of malignancies within 10 months. This study suggests that a number of functional adrenal tumors are possibly left undiagnosed until found incidentally, and that CT is the most powerful tool to detect adrenal tumors. Our data did not support surgical intervention in cases of metastatic adrenal tumors.

Adolescent↗
PubMed1995

Inhibition by carbamazepine of various ion channels-mediated catecholamine secretion in cultured bovine adrenal medullary cells.

The effects of carbamazepine (CBZ) on 22Na+ influx, 45Ca2- influx, catecholamine secretion and cyclic GMP production were examined in cultured bovine adrenal medullary cells. 1) CBZ (40-120 mumol/l) inhibited 22Na+ influx evoked by carbachol in a concentration-dependent manner. CBZ inhibited carbachol-evoked 45Ca2- influx and catecholamine secretion at concentrations similar to those which suppressed 22Na+ influx. 2) CBZ (4-120 mumol/l) inhibited veratridine-induced 22Na+ influx, 45Ca2+ influx and catecholamine secretion. 3) CBZ (12 or 40-120 mumol/l) suppressed 56 mmol/l K(+)-evoked 45Ca2+ influx and catecholamine secretion, respectively. 4) Combination of CBZ with nitrendipine or omega-agatoxin-IVA produced further inhibition of 56 mmol/l K(+)-evoked 45Ca2+ influx and catecholamine secretion, compared to the effect of CBZ alone, whereas CBZ plus omega-conotoxin-GVIA did not produce any further inhibition. 5) CBZ (40 mumol/l) attenuated the production of cyclic GMP caused by muscarine. These results suggest that CBZ at therapeutic concentrations (16-48 mumol/l; 4-12 micrograms/ml) inhibits catecholamine secretion by interfering with nicotinic acetylcholine receptor-associated ion channels, voltage-dependent Na+ channels and N-type voltage-dependent Ca2+ channels, and may have an antimuscarinic effect in adrenal medullary cells.

Adrenal Medulla↗
PubMed1995

The expression of Na+/K(+)-ATPase beta-subunit cRNA injected into Xenopus oocytes is affected by coinjection with alpha-subunit cRNA.

The cRNA for Torpedo californica Na+/K(+)-ATPase beta-subunit (cRNA beta) was injected into Xenopus oocytes alone or with the cRNA for the Na+/K(+)-ATPase alpha-subunit (cRNA alpha). When cRNA beta was injected alone, the amount of the beta-subunit that accumulated in oocytes increased with increasing amounts of injected cRNA beta. When cRNA beta and cRNA alpha were injected simultaneously, less beta-subunit accumulated than when cRNA beta was injected alone, whereas the Na+/K(+)-ATPase activity increased markedly. The decrease in the accumulation of the beta-subunit was dose-dependent upon the cRNA alpha. The mutant beta-subunit unable to assemble with the alpha-subunit accumulated in oocytes independently of cRNA alpha, suggesting that post-translational control mechanisms may serve to reduce the accumulation of the beta-subunit.

Animals↗
PubMed1995

Adrenomedullin increases cyclic AMP more potently than CGRP and amylin in rat renal tubular basolateral membranes.

In rat renal tubular basolateral membranes, the potency to increase cAMP of adrenomedullin (AM), a novel vasorelaxant peptide originally isolated from human pheochromocytoma, was compared with those of calcitonin gene-related peptide (CGRP) and amylin. Although all three peptides raised cAMP in a time- and concentration-dependent manner with a 4-fold increase at 10(-6)-10(-5) M, the EC50 value (10(-9) M) of AM was 100-fold smaller than those of CGRP and amylin. CGRP[8-37], an antagonist for CGRP receptors, attenuated cAMP elevation induced by these peptides with the essentially similar concentration-inhibition curves. These results suggest that the receptors for AM, CGRP and amylin share a common structural homology, and that the receptors sensitive to AM are preferentially expressed in renal tubular basolateral membranes.

Adrenomedullin↗
PubMed1995

Functional consequences of substitution of the disulfide-bonded segment, Cys127-Cys150, located in the extracellular domain of the Na,K-ATPase beta subunit: Arg148 is essential for the functional expression of Na,K-ATPase.

The Cys127-Cys150 disulfide-bonded loop (L1) of the Torpedo californica Na,K-ATPase beta 1 subunit was substituted with the corresponding loop of the rat beta 1, mouse beta 2, or pig H,K-ATPase beta subunit. All the substituted mutant beta subunits assembled with the Na,K-ATPase alpha subunit in a trypsin-resistant manner. The mutants with L1 from the Na,K-ATPase beta subunit isoforms (rat beta 1 and mouse beta 2) each formed a functional complex with the Na,K-ATPase alpha subunit. On the other hand, the complex of the alpha subunit with the mutant beta subunit that was substituted with the pig H,K-ATPase beta subunit L1 was inactive as to ATP hydrolysis. Ser131 and Phe148 located within L1 of the pig H,K-ATPase beta subunit-substituted mutant were back-mutated to Pro131 and Arg148, respectively. The Phe148 to Arg mutation restored the ability of the mutant beta subunit substituted with the H,K-ATPase beta subunit L1 to form a functional complex with the alpha subunit. These results suggested that the Cys127-Cys150 loop of the Na,K-ATPase beta 1 subunit, especially Arg148, plays a critical role in the functional expression of Na,K-ATPase.

Amino Acid Sequence↗
PubMed1995

Stimulatory effect of interleukin-1 alpha on proliferation through a Ca2+/calmodulin-dependent pathway of a human thyroid carcinoma cell line, NIM 1.

NIM 1 cells, a human thyroid cell line established from a patient with thyroid papillary adenocarcinoma, produce cytokines such as interleukin-1 alpha (IL-1 alpha) and granulocyte-colony stimulating factor. In the present study, we investigated the signal transduction pathway in the proliferation of NIM 1 cells evoked by IL-1 alpha. Incubation of NIM 1 cells with IL-1 alpha for 48 h increased the incorporation of 3H-thymidine (3H-TdR). The stimulatory effect of IL-1 alpha was evident at 0.01 ng/ml and the maximal effect was seen at 10 ng/ml. IL-1 alpha evoked an influx of 45Ca into NIM 1 cells within 3 min in a concentration-dependent manner (0.01-1 ng/ml). These stimulatory effects of IL-1 alpha on both 3H-TdR incorporation and 45Ca influx were similarly inhibited by nicardipine, an inhibitor of voltage-dependent Ca2+ channels, in a concentration-dependent manner (10-1000 nM). The stimulatory effect of IL-1 alpha on 3H-TdR incorporation was inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), an antagonist of calmodulin, but not by 1-(5-isoquinoline sulfonyl)-2-methylpiperazine (H-7), an inhibitor of protein kinase C. While the culture medium initially contained 0.75 mM Ca2+, inhibition of 3H-TdR incorporation by nicardipine and W-7 under these baseline conditions was also recognized. These results suggest that IL-1 alpha stimulates cell proliferation through a Ca2+/calmodulin-dependent pathway in NIM 1 cells.

Biological Transport↗
PubMed1995

Plasma catecholamines and cyclic AMP response during head-up tilt test in patients with neurocardiogenic (vasodepressor) syncope.

To examine hemodynamic, plasma catecholamines, and cyclic AMP changes during tilt in patients with neurocardiogenic (vasodepressor) syncope, six patients underwent 80 degrees head-up tilt test for 10 minutes with isoproterenol infusion (1-3 micrograms/min). Venous blood was sampled in the supine position, at 3 minutes of tilt, and at the onset of vasodepressor reaction during tilt. All patients had previous tilt studies in which vasodepressor syncope had been induced reproducibly (mean 3.3 episodes in each patient). Syncope was induced at 6.1 +/- 0.4 minutes of tilt with an infusion of isoproterenol (mean 1.7 +/- 0.3 micrograms/min). Although arterial pressure and heart rate did not change significantly between in the supine position and at 3 minutes of tilt, plasma norepinephrine increased significantly at 3 minutes of tilt (0.44 +/- 0.10 ng/mL; P < 0.05) and at the onset of vasodepressor reaction (0.49 +/- 0.12 ng/mL; P < 0.01) compared to the supine position with isoproterenol (0.34 +/- 0.10 ng/mL). Also, cyclic AMP (cAMP) increased significantly at 3 minutes of tilt (25.3 +/- 2.0 pmol/mL; P < 0.005) and at the onset of vasodepressor reaction (29.6 +/- 1.7 pmol/mL; P < 0.005) compared to the supine position with isoproterenol (20.4 +/- 1.9 pmol/mL). After administration of selective beta 1-blocker, metoprolol (40 mg/day), plasma norepinephrine, and cAMP during tilt did not change significantly compared to baseline tilt. However, metoprolol prevented the syncope in 3 of 6 patients. After administration of beta 1-, beta 2-blocker, propranolol (30 mg/day), cAMP at 3 minutes of tilt decreased significantly compared to the baseline tilt (16.9 +/- 1.4 pmol/mL vs 25.3 +/- 2.0 pmol/mL; P < 0.05) and propranolol prevented the syncope in all six patients. We concluded that the increase of cAMP may play an important role for the induction of vasodepressor reaction in patients with neurocardiogenic (vasodepressor) syncope. The concentration of cAMP showed more sensitive response to vasodepressor reaction than that of norepinephrine.

Adrenergic beta-Agonists↗
PubMed1995

Differential changes in alpha- and beta-adrenoceptors in the cerebral cortex and hippocampus of the Mongolian gerbil after unilateral brain ischemia.

BACKGROUND AND PURPOSE: Changes in adrenoceptors in the cerebral cortex and hippocampus of Mongolian gerbils after brain ischemia were investigated. METHODS: Twenty-four hours after unilateral occlusion of the common carotid artery, alpha 1-, alpha 2-, and beta-receptors of the membrane fraction of the cerebral cortex or the hippocampus were analyzed by binding assay with the use of [3H]prazosin, [3H]p-aminoclonidine, and [125I]cyanopindolol as radioligands, respectively. RESULTS: In the cerebral cortex, the number of binding sites (Bmax) and the dissociation constant (Kd) of [3H]prazosin were not altered, whereas the Bmax value of [3H]p-aminoclonidine binding was decreased by 30% and that of [125I]cyanopindolol binding by 16% without a change in Kd values for the ligands. In the hippocampus, the Bmax values of [3H]prazosin, [3H]p-aminoclonidine, and [125I]cyanopindolol bindings were decreased by 21%, 53%, and 19%, respectively, but there was no change in the Kd values for the ligands. The bindings of [3H]prazosin and [3H]p-aminoclonidine of the contralateral side of the cerebral cortex and the hippocampus were not altered by ischemia, but that of [125I]cyanopindolol was decreased when compared with normal tissues. CONCLUSIONS: These results show that ischemia results in a decrease in brain alpha 1-, alpha 2-, and beta-adrenoceptors to various degrees, depending on the brain area and the types of receptors, and suggest that vulnerability of the brain to ischemia is different depending on brain areas and that the regulatory mechanisms of alpha 1-, alpha 2-, and beta-receptors are different.

Animals↗
PubMed1995

Effect of cAMP-dependent protein kinase on catecholamine secretion from bovine adrenal chromaffin cells.

We examined the role of cAMP-dependent protein kinase in Ca(2+)-elicited catecholamine secretion from bovine adrenal chromaffin cells. When the digitonin-treated cells were incubated with the catalytic subunit of cAMP-dependent protein kinase, the secretion of catecholamines from the cells occurred in the absence of Ca2+. The effect of the catalytic subunit was dependent on its activity (50-100 units/ml) and the presence of ATP-Mg2+ in the incubation medium. However, incubation of the cells with the regulatory subunit of cAMP-dependent protein kinase did not affect the secretion. Ca2+ (43 nM-10 microM) also increased the secretion, which was ATP-Mg(2+)-dependent. The catalytic subunit (25-200 units/ml) enhanced the Ca(2+)-evoked secretion at the suboptimal but not optimal Ca2+ concentration, which induced maximal secretion. A potent synthetic peptide inhibitor of cAMP-dependent protein kinase abolished the catalytic subunit-induced secretion, but not the Ca(2+)-evoked secretion. On the other hand, K-252a, a potent inhibitor of protein kinases, inhibited both the catalytic subunit-induced and the Ca(2+)-evoked secretion, but not KT5823, a much less potent inhibitor of protein kinases. These results strongly suggest that the catalytic subunit of cAMP-dependent protein kinase produces the secretion of catecholamines via protein phosphorylation. The results further suggest that the cAMP-dependent protein kinase does not participate in an intrinsic process of Ca(2+)-elicited secretion but it may act as a modulator.

Adrenal Cortex↗
PubMed1994

Pituitary adenylate cyclase-activating polypeptides (PACAPs) increase cAMP in rat cerebral microvessels.

Effect of PACAP on cAMP level in the rat cerebral microvessels was investigated. The cerebral microvessels were prepared from rat cerebral cortex by albumin flotation and glass beads filtration technique. When the microvessels were incubated with PACAP 27, PACAP 38 and VIP, cAMP in the microvessels was increased rapidly reaching a plateau value within 60 s. PACAP 27, PACAP 38 and VIP increased cAMP level in a dose-dependent manner with EC50 values of 4.7, 7.0 and 34 nM, respectively. These results suggest that PACAPs play a role in the regulation of the cerebral microvessel function.

Animals↗