Biomedical subjects

T Nakane

Publications and source records attributed to T Nakane.

At least 55 records · Page 3Linked to original sources

PubMed1996

Purinergic and adrenergic transmission and their presynaptic modulation in canine isolated perfused splenic arteries.

Vasoconstrictions induced by periarterial electrical stimulation were analysed pharmacologically in the canine isolated perfused splenic artery. Phentolamine enhanced the vasoconstrictions at 1 Hz but inhibited those at 10 Hz. Suramin and P2x purinoceptor desensitization with alpha,beta-methylene ATP abolished the phentolamine-enhanced and -resistant vasoconstrictions. alpha,beta-Methylene ATP inhibited the vasoconstrictions at 1 Hz and by exogenous ATP but did not change those at 10 Hz and by exogenous noradrenaline. Suramin reduced the vasoconstrictions by the electrical stimulations and alpha,beta-methylene ATP but did not affect those by exogenous ATP. Prazosin did not affect the vasoconstrictions at 1 Hz but inhibited those at 10 Hz. Rauwolscine enhanced the prazosin-resistant vasoconstrictions. These results suggest that the electrical stimulation at 1 Hz releases purinergic transmitters (ATP or a closely related compound) as a dominant candidate for the vasoconstrictions, and a co-released noradrenaline may inhibit the release of purinergic transmitters through presynaptic alpha 2-adrenoceptors in the canine splenic artery.

Adenosine Triphosphate↗

PubMed1996

Immunolocalization of cellular glutathione peroxidase in adult rat lungs and quantitative analysis after postembedding immunogold labeling.

To determine the distribution of cellular glutathione peroxidase in rat lungs, the tissues were stained immunohistochemically. Quantitative analysis was performed in certain cell types of alveolar linings, after the ultrathin sections were stained by a postembedding immunogold technique. Immunoblot analysis revealed that homogenates of rat liver, heart, and lungs all gave a single band. Under the light microscope, the following tissues were stained intensely: epithelial cells, smooth muscle cells and glands of bronchi and bronchioles, type II alveolar cells, and alveolar macrophages. Under immunoelectron microscopy, type II alveolar cells and macrophages were abundant in mitochondria. The mitochondria, nucleus, and cytoplasm of macrophages were labeled almost twice as densely as the respective compartments of type II alveolar cells. Within cell types, the mitochondria were labeled twice as densely as the nuclei. The other particles were less than half as densely labeled as the nuclei. The labeling was slightly less dense in the cytoplasm than in the nucleus. The present study revealed that glutathione peroxidase occurred predominantly in the epithelial linings and metabolically active sites in rat lungs. The tissues that were previously found to be rich in superoxide dismutases were also rich in glutathione peroxidase.

Animals↗

PubMed1996

Immunohistochemical localization and quantitative analysis of cellular glutathione peroxidase in foetal and neonatal rat tissues: fluorescence microscopy image analysis.

To quantitate the developmental changes in selenium-dependent cellular glutathione peroxidase during the perinatal period, tissue sections from foetal (day 12 to day 22) and neonatal (day 6) rats were stained immunohistochemically using specific polyclonal antiserum. The intensity of the staining was quantified by fluorescence microscopy image analysis. There was a general trend of enriched glutathione peroxidase in the epithelial linings and metabolically active sites. Significant fluorescence was detected in cardiomyocytes, hepatocytes, renal tubular epithelium, bronchiolar epithelium and intestinal epithelium at day 15. The intensity increased in a stepwise manner thereafter. The overall increase in the intensity of staining in the heart, liver, kidneys, lungs and intestine was 1.5-, 2.3-, 1.6-, 1.7- and 3.0-fold, respectively. The phase of most rapid increase occurred during the foetal period in the liver, intestine and heart. In the kidneys and lungs, glutathione peroxidase increased significantly during foetal life, and to a similar extent postnatally. These results suggest that the intracellular H2O2-scavenging system develops during the foetal period as an essential mechanism for living under atmospheric oxygen conditions. The late development observed in the kidneys and lungs is consistent with the relative biological immaturity of these organs in full-term neonates.

Animals↗

PubMed1995

In vitro antibacterial activity of DU-6859a, a new fluoroquinolone.

The in vitro antibacterial activity of DU-6859a, a new fluoroquinolone, against a wide variety of clinical isolates was evaluated and compared with those of tosufloxacin, ofloxacin, ciprofloxacin, and sparfloxacin. DU-6859a showed potent broad-spectrum activity against gram-positive, gram-negative, and anaerobic bacteria, and its activity was greater than those of the control quinolones. By comparison of MICs at which 90% of strains are inhibited, DU-6859a had potent activity against bacteria resistant to the control quinolones. The time-killing curves of quinolones showed that the number of viable cells decreased rapidly during 2 to 4 of incubation, and regrowth was not seen even after 8 h incubation. At a concentration of four times the MIC, the frequencies of appearance of spontaneous mutants of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa resistant to DU-6859a were < or = 4.0 x 10(-9) to 1.9 x 10(-8). The 50% inhibitory concentrations of DU-6859a were 0.86 and 1.05 micrograms/ml for the supercoiling activities of DNA gyrases isolated from E. coli and P. aeruginosa, respectively. The rank order of the 50% inhibitory concentrations observed for both DNA gyrases roughly paralleled the MICs.

Anti-Infective Agents↗

PubMed1994

Serum antioxidant status in streptozotocin-induced diabetic rat.

To determine whether decrease in serum antioxidants contributes to the increased oxidative stress, we measured the antioxidant activity (AOA), total peroxyl radical-trapping antioxidant parameter (TRAP), and their component individual antioxidants in the serum of diabetic rats. AOA was assayed as the ability of serum to inhibit lipid autoxidation in brain homogenates. TRAP was assayed as the ability to delay lipid peroxidation induced by an azo initiator. Antioxidants measured were ceruloplasmin, unsaturated iron binding capacity (UIBC) and albumin as components of AOA; and uric acid, protein sulfhydryl and alpha-tocopherol as components of TRAP. AOA was decreased markedly in the diabetics due to the decrease in ceruloplasmin, UIBC and albumin. On the other hand, the directly measured TRAP in the diabetics was unaltered. Uric acid and alpha-tocopherol were increased in the diabetics. However, decrease in unidentified scavengers offset the increase brought about by those antioxidants These results suggest that the decreased metal binding capacity contributes to the increased oxidative stress in the diabetic rats.

Animals↗

PubMed1994

Differential effects of omega-conotoxin GVIA and tetrodotoxin on vasoconstrictions evoked by electrical stimulation and nicotinic receptor stimulation in canine isolated, perfused splenic arteries.

1. The effects of omega-conotoxin GVIA (omega-CgTX) and tetrodotoxin (TTX) on vasoconstrictions induced by acetylcholine (ACh) and nicotine were investigated and compared with those induced by periarterial electrical stimulation in the isolated and perfused canine splenic arteries. 2. ACh and nicotine at doses of 0.01 to 1 mumol constricted the splenic artery, dose-dependently. ACh induced consistent responses, but the vasoconstrictor responses to nicotine became significantly smaller with repeated administration of nicotine. 3. Periarterial electrical stimulation produced a vasoconstriction that was abolished by either TTX (30 nmol) or omega-CgTX (3 nmol), but the vasoconstrictor response to nicotine was not significantly affected by the same doses of TTX and omega-CgTX. Inhibitions by TTX and omega-CgTX of ACh-induced vasoconstrictions were small but statistically significant, showing that the percentage inhibition was less than 15%. TTX and omega-CgTX did not affect the vasoconstrictor responses to exogenous noradrenaline (NA). 4. ACh did not produce any vasoconstriction in the preparations treated either with alpha-adrenoceptor antagonists (10 microM bunazosin and 10 microM midaglizole) or with 30 microM guanethidine. NA-induced responses were abolished by alpha-adrenoceptor antagonists, but not affected by guanethidine treatment. 5. Vascular responses to ACh were completely inhibited by 1 mumol hexamethonium. In the preparations treated with 100 nmol nicotine, ACh did not produce any vasoconstriction. However, the NA-induced vasoconstriction was affected by neither hexamethonium nor nicotine treatment. 6. Atropine (1 microM) significantly inhibited but did not abolish the vasoconstrictor responses to ACh. The vascular responses to nicotine and NA were also significantly inhibited by atropine treatment. 7. These results indicate that (1) ACh constricts the splenic artery through the activation of presynaptic nicotinic receptors present on the sympathetic nerves; (2) differential effects of TTX and omega-CgTX on the vascular responses to ACh and nicotine, and to electrical stimulation suggest that the receptor-operated ion channels are mainly responsible for NA release induced by nicotinic receptor stimulation, but N-type VOCCs are responsible for that by electrical stimulation; (3) atropine may have an inhibitory action on nicotine-related responses, in addition to its inhibitory action on NA.

Acetylcholine↗

PubMed1994

Characteristics of the responses of isolated and perfused canine splenic arteries to vasoactive substances and to periarterially electrical stimulation.

Pharmacological characteristics of the canine isolated splenic artery were investigated by the cannula insertion method for observing vascular responses to vasoactive agents and periarterial nerve stimulation. Four alpha-adrenoceptor agonists and tyramine induced vasoconstrictions in a dose-dependent manner, and the order of potency was noradrenaline (NA) > phenylephrine > clonidine > methoxamine > tyramine. Xylazine (a selective alpha 2-adrenoceptor agonist) did not elicit any vasoconstriction. Several autacoids and KCl also constricted the splenic artery dose-dependently, and the order of potency was 5-hydroxytryptamine (5-HT) >> ATP = histamine >> KCl. The dose-response curves for clonidine and NA were shifted to the right by bunazosin (a selective alpha 1-adrenoceptor antagonist), but were not affected by midaglizole (a selective alpha 2-adrenoceptor antagonist). The parameters of electrical stimulation to elicit a clear and constant vasoconstriction were 0.2 msec of pulse duration, 6 V and 0.1 Hz. The vasoconstrictive responses to electrical stimulation at 6-12 V, 0.1-10 Hz and 0.2-1 msec of pulse duration were completely inhibited by tetrodotoxin (TTX) and strongly inhibited by guanethidine. The results in this study suggest that: 1) in contrast with other regional arteries, the canine splenic artery has an alpha 1-adrenoceptor-related and clonidine-sensitive vasoconstrictive response, 2) this artery has no functional postsynaptic alpha 2-adrenoceptors, 3) it may be easier to observe the vascular responses to vasoactive agents in the isolated and perfused arterial segments, and 4) the isolated and perfused canine splenic artery is useful as a preparation to study the sympathetic nerve transmission.

Adrenergic alpha-Agonists↗

PubMed1994

Primary Ewing's sarcoma of the skull base with intracerebral extension--case report.

A 32-year-old female presented with an uncommon primary Ewing's sarcoma of the skull involving the middle cranial fossa with an extremely unusual extension into the cerebral parenchyma. She was treated with surgical excision, irradiation, and chemotherapy. Two years after surgery she demonstrated no evidence of local recurrence or distant metastasis. Ewing's sarcoma of the skull may achieve a better survival rate under adequate management than this lesion in other sites.

Adult↗

PubMed1993

Characterization of 5-HT receptors in simian isolated gastroepiploic artery.

The vascular responses of simian gastroepiploic arteries to 5-hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5-CT, a selective 5-HT1-like receptor agonist), 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, a selective 5-HT1A receptor agonist), m-trifluoromethylphenylpiperazine (TFMPP, a selective 5-HT1B receptor agonist), noradrenaline and KCl were examined in isolated, cannulated and perfused preparations. 5-HT induced dose-dependent vasoconstrictions more potently than noradrenaline did. The rank order of potency was 5-HT > noradrenaline > 5-CT >> 8-OH-DPAT = TFMPP. 5-HT- and 5-CT-induced vasoconstrictions were not significantly changed by endothelial denudation, although acetylcholine-induced vasodilatations were abolished. 5-HT-induced vasoconstrictions were depressed by phentolamine (an alpha-adrenoceptor antagonist), diltiazem (a calcium ion channel inhibitor), methysergide (a 5HT1- and 5HT2-receptor antagonist) and ketanserin (a selective 5-HT2 receptor antagonist). Noradrenaline-induced vasoconstrictions were readily inhibited by phentolamine and ketanserin. 5-CT-, 8-OH-DPAT- and TFMPP-induced vasoconstrictions were inhibited by both methysergide and ketanserin. KCl-induced vasoconstrictions were blocked by diltiazem. From these results, we conclude that (1) the simian gastroepiploic artery contains 5-HT receptors, (2) 5-HT1-like and 5-HT2 receptors are involved in the vasoconstriction of the simian gastroepiploic artery, and (3) the vasoconstriction is at least partially related to the activation of calcium ion channels.

Animals↗

PubMed1993

Antioxidants in the serum of children with insulin-dependent diabetes mellitus.

To determine whether alteration in serum antioxidant status is related to the increased oxidative stress as a cause of diabetic angiopathy, we measured both the antioxidant activity (AOA) and total peroxyl radical-trapping antioxidant parameter (TRAP), and their component individual antioxidants in serum of children with insulin-dependent diabetes mellitus (IDDM). The AOA was measured as the ability to inhibit lipid autoxidation in brain homogenates. TRAP was assayed as the ability to delay lipid peroxidation induced by an azo initiator. Antioxidants measured were ceruloplasmin, transferrin, and albumin as components of AOA; and ascorbic acid, uric acid, protein sulfhydryl, and alpha-tocopherol as components of TRAP. Serum AOA appeared to be decreased in the diabetics in relation to poor glycemic control, corresponding to the decrease in transferrin and albumin. Serum haptoglobin level was also decreased in the diabetics. Similarly, the directly measured TRAP value was decreased in the diabetic serum mainly due to the decreased contribution of unidentified chain-breaking antioxidants, despite the increase in ascorbic acid and alpha-tocopherol. The decrease in both types of antioxidant activity in the diabetic serum, as new findings, suggests that a defective serum antioxidant status contributes to the increased oxidative stress in IDDM.

Adolescent↗

PubMed1993

In-vitro evaluation of the four beta-lactamase inhibitors: BRL42715, clavulanic acid, sulbactam, and tazobactam.

The in-vitro synergic activities of BRL42715, a new beta-lactamase inhibitor, clavulanic acid, sulbactam, and tazobactam combined with ampicillin, piperacillin, cephalothin, or cefoperazone were tested against various bacteria producing known types of beta-lactamase. BRL42715 showed the best synergistic activity among the inhibitors tested against strains producing penicillinases of type I, II, III, V, and that from Klebsiella pneumoniae, cephalosporinases, and oxyiminocephalosporinases (except that from Klebsiella oxytoca). Clavulanic acid combined with the beta-lactams tested showed the best synergic activity of the inhibitors against strains producing type IV penicillinase and oxyiminocephalosporinase from K. oxytoca. The 50% inhibitory doses of BRL42715 were superior to those of clavulanic acid against various types of beta-lactamases except for type IV penicillinase and the oxyiminocephalosporinase from K. oxytoca. The inhibitory activity of BRL42715 against cephalosporinases from various bacteria was 10(4) to 10(6)-fold greater than that of clavulanic acid. The synergic effects of BRL42715 and clavulanic acid on the activity of piperacillin were compared against six clinical isolates of bacteria resistant to piperacillin. The synergic activity of BRL42715 was greater than that of clavulanic acid in all six isolates.

Anti-Bacterial Agents↗

PubMed1993

Muscarinic receptor subtypes mediating vasodilation and vasoconstriction in isolated, perfused simian coronary arteries.

Using the cannula insertion method, we investigated the vascular responses of isolated simian coronary artery to acetylcholine (ACh). When the preparation was partially precontracted by 20 mM KCl, ACh and carbachol induced vasodilation dose dependently in coronary artery with endothelium, but ACh and carbachol contracted the coronary artery after removal of the endothelium by 1 mg saponin. A selective M1 receptor agonist 4-[N-(3-chlorophenyl)carbamoyloxy]-2-butinyltrimethylammonium++ + chloride (McN-A-343) did not affect the perfusion pressure of the precontracted coronary arteries significantly. Both these responses to ACh were inhibited by the M3 receptor antagonist 4-dipheny-lacetoxy N-methylpiperidine methobromide (4-DAMP) in a dose-dependent manner, but not by a selective M2 receptor antagonist AF-DX 116 (11-[[2-[(diethylamino)methyl]-1-piperidinyl] acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzo-diazepine-6-one). A selective M1 receptor antagonist pirenzepine did not affect ACh-induced vasoconstriction significantly and inhibited the vasodilation partially only at the highest dose (100 nmol). The effects of three antagonists on the vasodilative responses to carbachol were also studied and almost the same results were observed. Removal of the endothelium did not affect sodium nitroprusside (SNP)-induced vasodilation significantly. Pirenzepine, AF-DX 116, and 4-DAMP did not affect the action of isoproterenol. These data suggest that the vasodilation elicited by ACh is mediated by release of endothelium-derived relaxing factors (EDRF) consequent to the activation of M3 receptors on endothelial cells, and the constriction is mediated by stimulation of M3 receptors on smooth muscle cells in isolated simian coronary arteries.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗

PubMed1993

Mechanism of pindolol-induced vasoconstriction in isolated and perfused dog coronary arteries.

The mechanism of pindolol-induced vasoconstriction in isolated and perfused dog coronary arteries was studied. Single injections of pindolol (1-100 micrograms), propranolol (1-30 micrograms), and 5-hydroxytryptamine (5-HT, 0.001-1 microgram) produced a dose-related vasoconstriction in dog coronary arteries which were dilated by acetylcholine. l-Pindolol constricted coronary arteries, but d-pindolol did not. The responses to pindolol and propranolol were not affected by any of the following compounds (100 micrograms): bunazosin (a selective alpha 1-adrenergic antagonist), DG 5128 (a selective alpha 2-adrenergic antagonist), atropine (a muscarinic antagonist), chlorpheniramine (a selective H1-antagonist), cimetidine (a selective H2-antagonist), and ketanserin (a selective 5-HT2 antagonist). Methysergide (10 micrograms, a 5-HT1 and 5-HT2 antagonist) significantly reduced pindolol- and propranolol-induced vasoconstrictions, although it did not reduce norepinephrine-induced vasoconstriction in the presence of 5 microM propranolol. Methysergide (10 micrograms) and ketanserin (100 micrograms) significantly suppressed 5-HT-induced vasoconstriction. Diltiazem (100 micrograms, a calcium antagonist) and the incubation in Ca(2+)-free solution containing 1 mM EGTA for 1 hr significantly reduced the vasoconstrictions induced by pindolol and propranolol. The Ca(2+)-free solution containing 1 mM EGTA abolished the vasoconstriction induced by 5-HT in the presence of 1 microM ketanserine. In a solution containing 20 mM KCl, the vasoconstrictions caused by pindolol and propranolol were enhanced in dog coronary arteries. These results indicate that the direct contractile effects of pindolol on dog coronary arteries are mediated, at least partly, through 5-HT1-like receptors, but not through alpha-adrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1993

Pharmacological analysis of vasodilation induced by extracellular adenosine 3',5'-cyclic monophosphate in the isolated and perfused canine coronary artery.

We studied how extracellular cyclic AMP (cAMP) dilates the isolated and perfused canine coronary artery using pharmacological tools. Single injections of cAMP (1-1000 nmol), adenosine 3',5'-cyclic monophosphorothioate Sp-isomer (Sp-cAMPS) (10-1000 nmol, an agonist of the cell surface cAMP receptor in Dictyostelium discoideum and of cAMP-dependent protein kinase), adenosine (0.1-1000 nmol) and 5'-AMP (0.1-1000 nmol) dilated the canine coronary artery dose dependently. The potency order for vasodilation was adenosine > 5'-AMP > cAMP > Sp-cAMPS > 8-bromo-cyclic GMP > 3'-AMP > 8-bromo-cAMP > N6,O2'-dibutyryl-cAMP. 2'-Deoxy-cAMP, 2',3'-cAMP, guanosine, cGMP, 3'-GMP and 5'-GMP did not produce vasodilation. Adenosine antagonists such as aminophylline (1-100 microM, nonselective), 8-phenyltheophylline (0.1-10 microM, A1 selective), 8-cyclopentyl-1,3-dipropylxanthine (0.01-1 microM, A1 selective) and 3,7-dimethyl-1-proparglyxanthine (0.01-1 microM, A2 selective) shifted the dose-response curve of adenosine in parallel to the right, but they shifted that of cAMP to the right and downwards. 8-Phenyltheophylline (1 and 10 microM) inhibited the response to Sp-cAMPS (100 nmol) dose dependently. Aminophylline (10 microM) did not affect isoproterenol- and forskolin-induced vasodilations. Adenosine deaminase (3 U/ml) completely inhibited the response to adenosine, but not those to 5'-AMP, cAMP, 8-bromo-cAMP and Sp-cAMPS. 5'-Nucleotidase inhibitors, adenosine-5'-(alpha,beta-methylene) diphosphate (10 microM) and 5'-GMP (1 mM), inhibited the responses to cAMP and 5'-AMP, but not that to adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMed1992

Selective regulation of beta 2-adrenergic receptor gene expression by interleukin-1 in cultured human lung tumor cells.

The regulation of beta 1- and beta 2-adrenergic receptors (beta 1AR and beta 2AR) and receptor gene expression by interleukin-1 alpha (IL-1 alpha) was studied in cultured A549 human lung adenocarcinoma cells. The density and affinity of beta 1 AR and beta 2 AR were analyzed by computerized curve fitting of 125I-pindolol binding and its displacement by subtype selective antagonists. Steady state levels of receptor mRNAs were quantified by DNA excess solution hybridization assays. A549 cells in preconfluent cultures had fewer beta 1AR than beta 2AR (beta 1: 1.9 +/- 0.3 vs beta 2: 4.0 +/- 0.5 fmol/mg protein, means +/- SE), but lost most of their beta 2 AR upon reaching confluency (beta 1: 2.7 +/- 0.4, beta 2: 0.8 +/- 0.3 fmol/mg). Incubation of preconfluent cells for 24 hr with 20 pM of human recombinant IL-1 alpha did not modify the density of either of the beta AR subtypes. Similar incubations of confluent cells increased the density of beta 2 AR from 0.8 +/- 0.3 to 4.2 +/- 0.9 fmol/mg, while the density of beta 1 AR and the antagonist affinities of both receptors remained unaltered. The IL-1 alpha-induced increase in beta 2 AR density in confluent cells was antagonized in a concentration-dependent manner by a recombinant protein antagonist of type I IL-1 receptors (IC50: 0.2 nM). The IL-1 alpha-induced increase in beta 2AR density was preceded by an increase in the steady state level of beta 2AR mRNA, while levels of beta 1AR mRNA remained unchanged. IL-1 alpha increased the stability as well as the rate of transcription of beta 2AR mRNA. These findings demonstrate for the first time that activation of type I IL-1 receptors in A549 cells leads to a cell density-dependent, selective upregulation of beta 2AR, and that the mechanism of this effect involves increased formation and stability of the beta 2AR message.

Cell Count↗

PubMed1991

Anti-muscarinic effect of alinidine on acetylcholine-induced vasodilation in isolated and perfused dog coronary arteries.

The effect of alinidine, a bradycardic agent, on the vasodilator responses to acetylcholine was examined in isolated and perfused dog coronary arteries. Single injections of acetylcholine (10(-12)-10(-6) mol) and carbachol (10(-10)-10(-6) mol) produced dose-dependent vasodilations. The endothelial removal by a bolus injection of saponin (1 mg) inhibited those vasodilations. Alinidine (10(-6) M) shifted the dose-response curves of acetylcholine and carbachol to the right, but it did not affect those for isosorbide dinitrate, isoproterenol and adenosine. The rank order of potency of muscarinic antagonists for inhibiting the acetylcholine-induced vasodilation was 4-DAMP greater than or equal to atropine greater than AF-DX 116 greater than or equal to pirenzepine greater than alinidine. Alinidine was approximately 100 times less potent than atropine. Single injection of alinidine (10(-8)-10(-6) mol) dilated the dog coronary artery in a dose-related manner. The vasodilation was not affected by the pretreatment with phentolamine (10(-6) M), pindolol (10(-6) M), atropine (10(-6) M), chlorpheniramine (10(-6) M), cimetidine (10(-6) M) or methysergide (10(-6) M). These results suggest that alinidine has a weak anti-muscarinic effect on the endothelium-dependent vasodilation of the dog coronary artery.

Acetylcholine↗

PubMed1990

Effects of IL-1 and cortisol on beta-adrenergic receptors, cell proliferation, and differentiation in cultured human A549 lung tumor cells.

The effects of IL-1 and cortisol, and their interactions on the density of beta-adrenergic receptors (beta AR), cell proliferation, and the adherence of cells to plastic were studied in cultured human A549 lung tumor cells. The density of beta AR, assayed by 125I-pindolol binding, was increased two- to threefold by a 24-h incubation of the cells with IL-1 alpha, IL-1 beta, and TNF-alpha (EC50: 2.7, 8.2, and 24 pM, respectively), although a series of other cytokines and growth factors did not have this effect. Cortisol also increased beta AR density (EC50: 30 nM) and markedly potentiated the effects of IL-1 alpha, IL-1 beta, and TNF-alpha. Neither IL-1 nor cortisol influenced the proportion of cell surface vs internalized beta AR. The IL-1-induced increase in beta AR density was half-maximal after 6 h, was reversible at a similar rate, and was blocked by 1 microM of cycloheximide. The effect of IL-1 on beta AR was specific, as the density of glucocorticoid receptors, measured by 3H-dexamethasone binding, was reduced by IL-1. Both cortisol and IL-1 potentiated the isoproterenol-induced increase in cAMP accumulation. IL-1 inhibited cell proliferation and thymidine uptake, and increased the adherence of A549 cells to the plastic culture flask, as quantified by a cell detachment assay. The effect of IL-1 on cell adherence was not inhibited by cycloheximide. Cortisol decreased cell adherence and prevented the IL-1-induced increase in adherence. The results indicate that multiple effects of IL-1 in a cultured tumor cell line involve different mechanisms, suggesting heterogeneity of IL-1R and/or coupling of IL-1R to distinct, nuclear, and nonnuclear, effector pathways.

Cell Adhesion↗

PubMed1990

Adenosine constricts the isolated and perfused monkey coronary artery.

Adenosine constricted 37 of 58 isolated and perfused monkey coronary arteries, whereas it dilated dog coronary arteries in all cases. The vasoconstriction induced by 0.1-10 micrograms (0.37-37.4 nmol) of adenosine was examined, since adenosine in large doses produced tachyphylaxis. The adenosine-induced vasoconstriction was significantly attenuated by diltiazem (100 micrograms [0.24 mumol]), although it was not affected by aminophylline (100 micrograms [0.23 mumol]), phentolamine (100 micrograms [0.36 mumol]), or methysergide (10 micrograms [28 nmol]. Forty-minute treatment with indomethacin (5 x 10(-6) mol/l) completely prevented the adenosine-induced vasoconstriction, but it did not significantly inhibit vasoconstriction induced by KCl (3 mg [40 mumol])- or norepinephrine (NE, 0.1 micrograms [0.59 nmol]). These results suggest that: (1) adenosine constricts monkey coronary arteries by increasing Ca2+ influx across the smooth muscle cell membrane; (2) cyclooxygenase products may be involved in the adenosine-induced vasoconstriction; (3) adenosine receptors may not be involved in the vasoconstriction.

Adenosine↗