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1. |
Ca2+-lnduced Cortisol Secretion from Permeabilized Bovine Adrenocortical Cells: The Roles of Calmodulin, Protein Kinase C and Cyclic AMP |
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Pharmacology,
Volume 46,
Issue 4,
1993,
Page 181-192
Tomokazu Yoshida,
Mitsunobu Mio,
Kenji Tasaka,
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摘要:
In order to clarify the role of intracellular second messenger systems in the cortisol secretion from bovine adrenocortical (BAC) cells, the cells were permeabilized with β-escin and stimulated intracellularly with various compounds. When the permeabilized BAC cells were exposed to submicromolar concentrations of Ca2+, a prompt cortisol secretion was elicited in a concentration-dependent manner. As the cells were stimulated with 12-O-tetradecanoyl-phorbol-13-acetate and 1 oleoyl-2-acetyl-glycerol, slow but persistent cortisol secretion was elicited, but in the case of 4α-phorbol-12,13-didecanoate, no such effect was observed. The Ca2+-induced cortisol secretion was inhibited by simultaneous applications of calmodulin and protein kinase C (C kinase) inhibitors, but no significant inhibition was elicited by protein kinase A (A kinase) inhibitor. The results seem to indicate that in the Ca2+-induced cortisol secretion calmodulin may stimulate the initial stage, while C kinase may be involved mainly in the late phase of the secretion. In addition, cyclic AMP (cAMP) was also effective in activating cortisol secretion from permeabilized BAC cells. The cAMP-induced cortisol secretion was suppressed by an A kinase inhibitor but not affected by calmodulin or C kinase inhibitor. When Ca2+ and cAMP were added simultaneously at concentrations lower than those required to induce the cortisol secretion separately, a marked cortisol secretion was elicited, suggesting that a synergic action exists between Ca2+- and cAMP-activated systems. The Ca2+-induced cortisol secretion was suppressed by ruthenium red, an inhibitor of Ca2+ transport in the mitochondria. Although both NADP+ and NADPH elicited only a transient cortisol secretion, simultaneous addition of Ca2+ with NADP+ or NADPH caused a potent and sustained cortisol secretion. The augmentation due to Ca2+ on the NADP+ (or NADPH)-induced cortisol secretion was inhibited by the addition of a calmodulin inhibitor or a C kinase inhibitor, but no such effect was caused by A kinase inhibitor. From the present investigation, it was concluded that the Ca2+-dependent intracellular signal transduction may simulate the cortisol synthesis systems in the mitochondria of BAC cell
ISSN:0031-7012
DOI:10.1159/000139044
出版商:S. Karger AG
年代:1993
数据来源: Karger
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2. |
Effects of Calcium Antagonists on K+-Induced Contraction in Isolated Aorta from Diabetic and Age-Matched Control Rats |
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Pharmacology,
Volume 46,
Issue 4,
1993,
Page 193-197
J.B. Heijnis,
P.A. van Zwieten,
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摘要:
The effects of nifedipine, verapamil and diltiazem on K+-induced contraction were investigated in isolated aortic rings from diabetic and age-matched control rats. Six weeks after streptozotocin injection there was no significant difference between the maximum isometric contraction to KCl (80 mmol/l), when expressed per milligram tissue weight, in aortic rings from diabetic rats and those from controls. A concentration-dependent inhibition of the K+-induced contraction was observed for the three Ca antagonists in aortic rings from both diabetic and age-matched control rats. Notably, the K+-induced contraction in aortic preparations from diabetic rats was more sensitive to nifedipine compared to control preparations (pD2: 8.61 vs. 8.31, p < 0.05), while no significant change in sensitivity towards verapamil (pD2 0.05) or diltiazem (pD2 0.05) could be demonstrated. Our data indicate a greater interference of nifedipine with voltage-operated channels in diabetic aortas compared with controls. Since a similar antispasmodic activity was found for diltiazem and verapamil it might be specific for dihydropyridine Ca antagonists.
ISSN:0031-7012
DOI:10.1159/000139045
出版商:S. Karger AG
年代:1993
数据来源: Karger
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3. |
Effect of Chronic Treatment with Losartan Potassium (DuP 753) on the Elevation of Blood Pressure during Chronic Exposure of Rats to Cold |
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Pharmacology,
Volume 46,
Issue 4,
1993,
Page 198-205
Melvin J. Fregly,
Fabian Rossi,
Patricia Van Bergen,
Margarethe Brummermann,
Robert Cade,
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摘要:
Elevation of diastolic, systolic, and mean blood pressures and cardiac hypertrophy occur in rats exposed to cold (5°C) for 1-3 weeks. The renin-angiotensin-aldosterone system is believed to play a role in the development of cold-induced hypertension since plasma renin activity increases within the first 2 weeks, presumably initiating the hypertensive process, and then returns to control level. The present study was designed to assess the role of angiotension II (Ang II) in the hypertensive process by chronic administration of losartan potassium, an Ang II i receptor antagonist. Twenty-four rats were divided into four equal groups. After a 1-week control period, one group was kept at 25°C while the remaining three groups were exposed to cold (5°C). One of the cold-treated groups was untreated while the remaining two were given losartan in drinking water at a concentration calculated to provide 56 and 112 mg/kg/day. The untreated cold-exposed group had a significant elevation of systolic blood pressure within 1 week of exposure to cold. Losartan at both doses prevented the elevation of blood pressure and blocked both the dipsogenic and vascular responses to administration of Ang II. Exposure to cold increased food intake, urine output and water intake significantly above that of warm-adapted controls. Treatment with losartan tended to decrease each of these toward the level of controls. At the conclusion of the seventh week of exposure to cold, the rats were sacrificed and heart, kidneys, and brown fat removed and weighed. Chronic exposure to cold increased the weight of heart, kidneys, and brown fat above that of warm-adapted controls. Treatment with losartan failed to prevent the increases in these organ weights. Thus, although treatment with losartan prevented the elevation of systolic blood pressure induced by chronic exposure to cold, it did not prevent cardiac and renal hypertrophy and the increase in brown fat. It would appear that losartan does not affect these and that an elevation of blood pressure does not sustain th
ISSN:0031-7012
DOI:10.1159/000139046
出版商:S. Karger AG
年代:1993
数据来源: Karger
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4. |
Effect of Methylene Blue on Blood Pressure in Rats |
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Pharmacology,
Volume 46,
Issue 4,
1993,
Page 206-210
Side Oktay,
Filiz Onat,
Funda Karahan,
Inci Alican,
Uğur Özkutlu,
Berrak Ç. Yegen,
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摘要:
Methylene blue (MB) is a soluble guanylate cyclase inhibitor, and known as an endothelium-derived relaxing factor (EDRF) inhibitor in vitro. In the present study, it was demonstrated that intravenous administration of MB caused a dose-dependent hypertensive effect in rats. The hypertensive responses to the higher doses (10 and 20 mg/kg) of MB was followed by a reflex hypotension which did not appear in pithed rats. Nor-adrenaline depletion by reserpine pretreatment did not inhibit MB-induced hypertension, but abolished the hypotensive response. Both hypertensive and hypotensive phases were not altered by indometacin. These results may suggest that in vivo guanylate cyclase inhibition leads to an increase in blood pressure; prostaglandins and noradrenaline release from sympathetic nerve endings do not contribute to MB-induced hypertension and it may be due in part to the inhibition of EDRF.
ISSN:0031-7012
DOI:10.1159/000139047
出版商:S. Karger AG
年代:1993
数据来源: Karger
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5. |
Production of 15-HETE by Cultured Smooth Muscle Cells from Cerebral Artery |
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Pharmacology,
Volume 46,
Issue 4,
1993,
Page 211-223
Richard Schulz,
Christel Krueger,
V. Manickavel,
Joy A. Steele,
David A. Cook,
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摘要:
Hydroperoxyeicosatetraenoic acids (HPETEs) are potent vasoconstrictors which have been implicated in the pathogenesis of the delayed cerebrovascular spasm which follows subarachnoid haemorrhage. We have previously shown that one of their stable breakdown products, 15-hydroxyeicosatetraenoic acid (15-HETE), is the major lipoxygenase product released from isolated cerebral arteries. To investigate the vascular cell type responsible for their production we have established the culture of smooth muscle cells from cerebral arteries and have measured their release of HETEs upon stimulation with arachidonic acid. The cultured cells isolated from bovine cerebral arteries expressed smooth muscle phenotype as they stained positively for smooth muscle α-actin and not factor VIII-related antigen. Furthermore, these cells possessed the calcium and potassium conductances characteristic of smooth muscle cells. Upon incubation with arachidonic acid, the major lipoxygenase product was 15-HETE; no leukotrienes were detected. The formation of 15-HETE was concentration-dependent and was attenuated by nordihydroguaiaretic acid, but not by indometacin. Similar to intact cerebral artery, cultured cerebrovascular smooth muscle cells have lipoxygenase activity, the major product of which is 15-HETE. These results are consistent with a possible role of the HPETEs in the pathogenesis of cerebral vasospasm
ISSN:0031-7012
DOI:10.1159/000139048
出版商:S. Karger AG
年代:1993
数据来源: Karger
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6. |
Ro 5-4864 and PK 11195, but Not Diazepam, Depress Cardiac Function in an Isolated Working Rat Heart Model |
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Pharmacology,
Volume 46,
Issue 4,
1993,
Page 224-230
Yeouda Edoute,
Jacob Giris,
Shlomo A. Ben-Haim,
Amanda Lochner,
Abraham Weizman,
Gal Hayam,
Yeshayahu Katz,
Moshe Gavish,
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摘要:
The present study was designed to investigate the effects of diazepam, a benzodiazepine (BZ) with high affinity to central BZ receptors and moderate affinity to mitochondiral BZ receptors, and of Ro 5-4864 and PK 11195, ligands specific for mitochondrial BZ receptors, on cardiac function in the isolated working rat heart model. Five concentrations of these drugs (10–9–10–5 mol/l) were used, and the chronotropic (heart rate) and inotropic [maximum elastance of the left ventricle at end systole (Emax), maximal first derivative of left ventricular (LV) pressure (dP/dtmax), LV pressure at dP/dtmax (pressure at dP/dtmax), aortic flow, stroke work, and total pressure-volume area] cardiac parameters were measured. Diazepam, Ro 5-4864, and PK 11195 showed no significant chronotropic activity up to 10–5 mol/l. Diazepam did not alter the inotropic properties of the heart. Ro 5-4864 at 10–5 mol/l significantly decreased the indices of contractility, namely, Emax, dP/dtmax, and pressure at dP/dtmax. Aortic flow, stroke work, and total pressure-volume area were significantly depressed at the same concentration. The negative inotropism of PK 11195 appeared to be identical, by most indices, to that of Ro 5-4864, both qualitatively (same pattern) and quantitatively (similar maximal variations); however, for some indices a depressant effect was also found at 10–7 mol/l. These results show that at high concentrations Ro 5-4864 and PK 11195, but not diazepam, have a depressant effect on mechanic
ISSN:0031-7012
DOI:10.1159/000139049
出版商:S. Karger AG
年代:1993
数据来源: Karger
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7. |
Inhibitory Cholinergic Effects of Esaprazole on Gastric Secretion and Plasma Gastrin Levels in the Dog |
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Pharmacology,
Volume 46,
Issue 4,
1993,
Page 231-240
Corrado Blandizzi,
Grazia Mengozzi,
Luigi Intorre,
Giianfranco Natale,
Giulio Soldani,
Mario Del Tacca,
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摘要:
The effects of esaprazole, a novel antiulcer drug, on gastric acid secretion and plasma gastrin levels were investigated in dogs provided with a gastric fistula or Heidenhain pouch. Esaprazole affected in a different extent the tests performed on dogs with a gastric fistula. The greatest inhibitory effect was obtained against 2-deoxy-D-glucose-induced acid output and gastrin release. An intermediate inhibition by esaprazole was detected on bethanechol-evoked secretion, and the lowest activity was found versus histamine-stimulated secretion. All these responses were strongly inhibited by the antimuscarinic drug pirenzepine used as reference drug. Moreover, both esaprazole and pirenzepine prevented the acid secretory response to a test meal in dogs with a Heidenhain pouch, without significantly affecting plasma gastrin levels. The present results suggest that the depressant action of esaprazole on gastric secretion depends on its peripheral anticholinergic activity, consisting of a partial blockade of acid output and a main reduction of vagally mediated gastrin release. On the basis of these findings, the antiulcer activity of esaprazole might be in part ascribed to its inhibitory effects on gastric secretion.
ISSN:0031-7012
DOI:10.1159/000139050
出版商:S. Karger AG
年代:1993
数据来源: Karger
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