Clinical and Experimental Pharmacology and Physiology最新文献

{"title":"Ganglion blockade does not prevent cortisol-induced hypertension in man.","authors":"Paula M Williamson,&nbsp;Sim Hom Tam,&nbsp;John J Kelly,&nbsp;Judith A Whitworth","doi":"10.1111/j.1440-1681.2005.04220.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.2005.04220.x","url":null,"abstract":"<p><p>1. The aim of the present study was to assess the effect of ganglion blockade on blood pressure in cortisol treated human subjects. 2. Four healthy male subjects were treated with cortisol 80 mg/day for a 5-day period. Ganglion blockade was achieved by intravenous trimethaphan. 3. Ganglion blockade did not significantly alter blood pressure in the pretreatment phase or on the last day of cortisol treatment. 4. Taken together with our previous observations that sympathetic activity is unaltered or reduced by cortisol, these results suggest that cortisol induced hypertension in humans is not a result of overactivity of the autonomic nervous system.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"32 4","pages":"294-6"},"PeriodicalIF":0.0,"publicationDate":"2005-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.2005.04220.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25041796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute effects of hydrocortisone on plasma nitrate/nitrite activity and forearm vasodilator responsiveness in normal human subjects.","authors":"Paula M Williamson,&nbsp;Johanna L Kohlhagen,&nbsp;George J Mangos,&nbsp;Judith A Whitworth,&nbsp;John J Kelly","doi":"10.1111/j.1440-1681.2005.04173.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.2005.04173.x","url":null,"abstract":"<p><p>1. The aim of the present study was to examine the acute effects of cortisol infusion on plasma nitrate/nitrite (NO) activity and forearm vascular responsiveness to acetylcholine. 2. We performed two randomized, placebo-controlled, cross-over studies. Study A examined the effects of intravenous hydrocortisone (200 mg over a 3 h period) on blood pressure (BP) and plasma NO activity in six healthy male volunteers. Study B examined the effects of intra-arterial hydrocortisone on cholinergic vasodilator responsiveness in six healthy male volunteers. Vasodilator responsiveness was measured by bilateral strain gauge plethysmography. 3. In study A, there was no significant change in BP during the hydrocortisone infusion. Comparing values obtained following 180 min infusion of hydrocortisone and control, there were significant increases in plasma cortisol (3441 +/- 342 vs 209 +/- 29 nmol/L, respectively; P < 0.001) and glucose (5.7 +/- 0.2 vs 4.6 +/- 0.2 mmol/L, respectively; P < 0.05) and a reduction in plasma renin concentration (PRC) (8.1 +/- 1.2 vs 11.0 +/- 1.8 pg/mL, respectively; P < 0.05) following hydrocortisone infusion. However, there were no significant changes in either plasma NO or in the endogenous NO synthase inhibitors asymmetrical and symmetrical dimethylarginine. 4. In study B, there was no significant change in BP or in cholinergic vasodilator responsiveness during the hydrocortisone infusion. 5. Short-term cortisol infusions do not alter biochemical or physiological markers of NO activity. If cortisol-induced hypertension is mediated by suppression of NO activity in humans, it seems likely that these changes take more than 3 h to become detectable.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"32 3","pages":"162-6"},"PeriodicalIF":0.0,"publicationDate":"2005-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.2005.04173.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24984707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidized low-density lipoprotein-induced apoptosis is attenuated by insulin-activated phosphatidylinositol 3-kinase/Akt through p38 mitogen-activated protein kinase.","authors":"Shun-ichi Nihei,&nbsp;Kazuhito Yamashita,&nbsp;Hiromi Tasaki,&nbsp;Kiyoshi Ozumi,&nbsp;Yasuhide Nakashima","doi":"10.1111/j.1440-1681.2005.04177.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.2005.04177.x","url":null,"abstract":"<p><p>1. The aim of the present study was to investigate whether p38 mitogen-activated protein kinase (p38 MAPK) is involved in oxidized low-density lipoprotein (oxLDL)-induced apoptosis of human umbilical vein endothelial cells (HUVECs). We also sought to determine whether this apoptosis is regulated by the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. 2. Low-density lipoprotein was oxidized with CuSO4 and used as oxLDL. Using HUVEC, we determined whether LDL/oxLDL induces apoptosis by DNA fragmentation and the cell cycle distribution (SubG1 method). The mechanism and activation of p38 MAPK and Akt were determined by western blot analysis. 3. The results showed that oxLDL induced DNA fragmentation, whereas cell cycle distribution showed that it also significantly increased the rate of cell death compared with the LDL group. SB203580 significantly inhibited cell death induced by oxLDL, as did the administration of insulin. Western blot analysis showed the activation of p38 MAPK by oxLDL, but not with LDL. It was found that Akt was activated in the presence of insulin. In the presence of either SB203580 or insulin, activation of p38 MAPK was significantly inhibited compared with stimulation by oxLDL alone. However, application of both insulin and wortmannin resulted in no significant difference compared with HUVEC stimulated by oxLDL only. 4. The results showed that apoptosis in HUVEC can be induced by oxLDL and involves p38 MAPK. It was also demonstrated that insulin inhibited oxLDL-induced apoptosis and may inhibit the activation of p38 MAPK through the PI3K/Akt pathway.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"32 3","pages":"224-9"},"PeriodicalIF":0.0,"publicationDate":"2005-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.2005.04177.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24985097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of heme oxygenase/carbon monoxide pathway on the vascular response to noradrenaline in portal hypertensive rats.","authors":"M A Erario,&nbsp;S Gonzales,&nbsp;S Romay,&nbsp;F X Eizayaga,&nbsp;J L Castro,&nbsp;A Lemberg,&nbsp;M L Tomaro","doi":"10.1111/j.1440-1681.2005.04171.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.2005.04171.x","url":null,"abstract":"<p><p>1. Portal hypertension (PH), a major syndrome in cirrhosis, producing hyperdynamic splanchnic circulation and hyperaemia. In order to elucidate the contribution of heme oxygenase to the vascular hyporeactivity, we assessed the activity of heme oxygenase-1 (HO-1), measured the in vivo pressure response to noradrenaline (NA) and investigated the effects of blocking the carbon monoxide (CO) and nitric oxide (NO) pathways in a prehepatic model of PH in rats. 2. Portal hypertension was induced by partial portal vein ligation (PPVL). Noradrenaline was injected intravenously. Liver, spleen and mesentery homogenates were prepared for measurement of HO-1 activity and expression. Four groups of rats were used: (i) a sham group; (ii) a PPVL group; (iii) a sham group pretreated with Zn-protoporphyrin IX (ZnPPIX); and (iv) a PPVL group pretreated with ZnPPIX. Each group was studied before and after treatment with the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). 3. For basal pressures and the pressure response to NA, inhibition of CO and NO pathways by ZnPPIX and L-NAME, respectively, produced an increase in mean arterial pressure (MAP) in sham-operated and in PH rats. Similarly, when both inhibitors were used together in either sham or PPVL rats, a greater increase in MAP was observed. 4. These results, together with the increased HO-1 activity and expression only in the PH group, have led us to suggest that the heme oxygenase/CO pathway is involved in the vascular response to NA in PH rats.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"32 3","pages":"196-201"},"PeriodicalIF":0.0,"publicationDate":"2005-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.2005.04171.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24985147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of calcineurin increases monocarboxylate transporters 1 and 4 protein and glycolytic enzyme activities in rat soleus muscle.","authors":"Masataka Suwa,&nbsp;Hiroshi Nakano,&nbsp;Shuzo Kumagai","doi":"10.1111/j.1440-1681.2005.04176.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.2005.04176.x","url":null,"abstract":"<p><p>1. The present study was designed to examine the role of calcineurin in muscle metabolic components by the administration of the specific calcineurin inhibitor cyclosporine A (CsA) to rats. 2. Male Wistar rats were divided into either a CsA-treated group (CT) or a vehicle-treated group (VT). Cyclosporine A was administered subcutaneously to rats at a rate of 25 mg/kg bodyweight per day for 10 successive days. Thereafter, changes in muscle enzyme activities and glucose transporter (GLUT)-4 and monocarboxylate transporter (MCT)-1 and MCT-4 proteins in the slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles were examined. 3. There was a significant increase in MCT-1 and MCT-4 proteins in the soleus muscle in the CT group, but not in the EDL muscle. The activities of hexokinase, pyruvate kinase and lactate dehydrogenase in the soleus muscle also increased significantly in the CT group, but a similar increase in enzyme activity was not seen in EDL muscle. The activities of citrate synthase or malate dehydrogenase and the GLUT-4 protein content were not altered by CsA treatment in either the soleus or EDL muscles. 4. These results seem to imply that calcineurin negatively regulates the components of glucose/lactate metabolism, except for GLUT-4, especially in slow-twitch muscle.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"32 3","pages":"218-23"},"PeriodicalIF":0.0,"publicationDate":"2005-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.2005.04176.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24985150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the potential of xenobiotic-metabolising enzymes as biocatalysts: evolving designer catalysts from polyfunctional cytochrome P450 enzymes.","authors":"Elizabeth M J Gillam","doi":"10.1111/j.1440-1681.2005.04165.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.2005.04165.x","url":null,"abstract":"<p><p>1. Biological catalysts have the advantage of being able to catalyse chemical reactions with an often exquisite degree of regio- and stereospecificity in contrast with traditional methods of organic synthesis. 2. The cytochrome P450 enzymes involved in human drug metabolism are ideal starting materials for the development of designer biocatalysts by virtue of their catalytic versatility and extreme substrate diversity. Applications can be envisaged in fine chemical synthesis, such as in the pharmaceutical industry and bioremediation. 3. A variety of techniques of enzyme engineering are currently being applied to P450 enzymes to explore their catalytic potential. Although most studies to date have been performed with bacterial P450s, reports are now emerging of work with mammalian forms of the enzymes. 4. The present minireview will explore the rationale and general techniques for redesigning P450s, review the results obtained to date with xenobiotic-metabolising forms and discuss strategies to overcome some of the logistic problems limiting the full exploitation of these enzymes as industrial-scale biocatalysts.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"32 3","pages":"147-52"},"PeriodicalIF":0.0,"publicationDate":"2005-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.2005.04165.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24984705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of 15-deoxy-Delta12,14-prostaglandin J2 on the expression of Toll-like receptor 4 and 2 in the murine lung in the presence of lipopolysaccharide.","authors":"Ken-ichiro Inoue,&nbsp;Hirohisa Takano,&nbsp;Rie Yanagisawa,&nbsp;Takamichi Ichinose,&nbsp;Kaori Sadakane,&nbsp;Shin Yoshino,&nbsp;Kouya Yamaki,&nbsp;Kazuhiko Uchiyama,&nbsp;Toshikazu Yoshikawa","doi":"10.1111/j.1440-1681.2005.04175.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.2005.04175.x","url":null,"abstract":"<p><p>1. Previously, we have demonstrated that 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) enhances acute lung injury induced by lipopolysaccharide (LPS) in mice. The enhancement in acute lung injury by 15d-PGJ2 was concomitant with the enhanced expression of several pro-inflammatory cytokines in the lung. However, other underlying mechanisms of this enhancement remain to be elucidated. The present study investigated the effects of 15d-PGJ2 on the expression of Toll-like receptor (TLR) 4 and 2 in the lung in the absence or presence of LPS. 2. In the present study, ICR mice were divided into four experimental groups that received (intratracheally) vehicle, LPS (125 microg/kg), 15d-PGJ2 (1 mg/kg) or 15d-PGJ2 + LPS. The mRNA expression of both TLR4 and 2 in the lung was evaluated 4 h after intratracheal administration. 3. 15-Deoxy-Delta12,14-prostaglandin J2 enhanced the mRNA expression of both TLR4 and 2 in the presence of LPS. 4. These results suggest that the enhancing effects of 15d-PGJ2 on LPS-induced acute lung injury may be explained, at least in part, by its effect on the lung expression of TLR4 and 2.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"32 3","pages":"230-2"},"PeriodicalIF":0.0,"publicationDate":"2005-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.2005.04175.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24985098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experimental and clinical study of the combined effect of arterial stiffness and heart rate on pulse pressure: differences between central and peripheral arteries.","authors":"Theodoros G Papaioannou,&nbsp;Athanassios Protogerou,&nbsp;Christos Papamichael,&nbsp;Dimitrios Mathioulakis,&nbsp;Sokratis Tsangaris,&nbsp;Emmanouil Karatzis,&nbsp;Savvas Toumanidis,&nbsp;Nicolaos Zakopoulos,&nbsp;John Lekakis","doi":"10.1111/j.1440-1681.2005.04174.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.2005.04174.x","url":null,"abstract":"<p><p>1. Pulse pressure (PP) constitutes an independent predictor of cardiovascular events and mortality in various populations. Heart rate (HR) and arterial stiffness, in addition to their independent predictive value for cardiovascular complications, seem to interact with regard to the modification of PP. The aim of the present study was to investigate the association of PP with HR under different levels of arterial compliance (AC), revealing their synergistic effects. 2. Seventy-one normotensive and untreated hypertensive subjects were examined. Arterial compliance was measured by the 'area' method, whereas central blood pressures and wave reflections were evaluated using the Sphygmocor system (AtCor Medical, Sydney, NSW, Australia). A hydraulic Windkessel model was also used to evaluate the independent effect of HR and AC on PP. Peripheral PP was associated only with mean pressure and AC. In contrast, central PP was further related to HR (20 b.p.m. decrease in HR resulted in central PP augmentation by 5.6 mmHg) regardless of mean pressure, stroke volume, age and gender. However, this association was statistically significant only for subjects with lower AC (< 1.1 mL/mmHg) and not for those with more compliant arteries. These findings are also in accordance with the experimental data. 3. Aortic PP is affected to a greater degree by HR changes compared with peripheral PP. This response was observed only at high levels of arterial stiffness. 4. The present study provides the first evidence regarding the combined effect of AC and HR on aortic PP, which may lead to larger clinical or epidemiological studies aiming to optimization of drug treatment and to a possible reduction of cardiovascular risk.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"32 3","pages":"210-7"},"PeriodicalIF":0.0,"publicationDate":"2005-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.2005.04174.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24985149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of uninephrectomy on renal structural properties in spontaneously hypertensive rats.","authors":"Hiroyuki Kinuno,&nbsp;Fumihiro Tomoda,&nbsp;Tsutomu Koike,&nbsp;Masanobu Takata,&nbsp;Hiroshi Inoue","doi":"10.1111/j.1440-1681.2005.04167.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.2005.04167.x","url":null,"abstract":"<p><p>1. To investigate effects of a reduction in nephron numbers on renal structural properties in hypertension, either unilateral nephrectomy (UNX) or sham operation (SO) was performed at 5 weeks of age in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats (n = 9 for each operation for each strain). 2. At 10-12 weeks of age, flow-pressure (F-P) and pressure-glomerular filtration rate (P-GFR) relationships were determined for maximally vasodilated, perfused kidneys. Kidneys were then perfusion fixed for histological analysis. 3. In the SO groups, the slope of F-P (minimal renal vascular resistance, reflecting overall luminal dimensions of pre- and post-glomerular vasculature) was greater in SHR than in WKY rats. The threshold pressure for beginning filtration at P-GFR (preglomerular to post-glomerular vascular resistance ratio) was higher in SHR than in WKY rats, but the slope of P-GFR (glomerular filtration capacity) did not differ between the two strains. These results suggest that vascular narrowing occurred, especially in the preglomerular resistance vessels in the kidneys of SHR, although glomerular filtration capacity was normal. 4. In UNX animals, the following results were obtained: (i) the slope of F-P was not affected in either strain; (ii) the pressure for beginning filtration at P-GFR was unchanged in WKY rats, but was decreased in SHR; (iii) the slope of P-GFR increased in WKY rats, but a compensatory adaptive increase was missing in SHR; and (iv) histologically, small increases in the luminal cross-sectional area of interlobular arteries and glomerular tuft area were observed in both strains. However, the increase in vascular lumen was more pronounced in SHR, whereas glomerular enlargement was greater in WKY rats. 5. These results suggested that UNX attenuates vascular narrowing of the preglomerular resistance vessels and glomerular structural adaptations to UNX (i.e. increased filtering capacity and glomerular enlargement) are impaired in SHR.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"32 3","pages":"173-8"},"PeriodicalIF":0.0,"publicationDate":"2005-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.2005.04167.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24984708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sphingosine kinase signalling in immune cells.","authors":"Tay Hwee Kee,&nbsp;Patricia Vit,&nbsp;Alirio J Melendez","doi":"10.1111/j.1440-1681.2005.04166.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.2005.04166.x","url":null,"abstract":"<p><p>1. Sphingolipids are potent second messengers modulating biochemical intracellular events and acting as ligands to mediate extracellular systems. Sphingosine kinase (SPHK) is the enzyme that phosphorylates sphingosine into sphingosine-1-phosphate (S1P), a potent bioactive sphingolipid. 2. The fact that SPHK is highly conserved from protozoa to mammals and is ubiquitous in living tissues reveals important roles of the SPHK pathway for the maintenance of health maintenance. This is also supported by comprehensive reviews on features of its main product, S1P, as having intracellular as well as extracellular roles, inducing a wide range of physiological responses from triggering Ca2+ release from internal stores to promoting growth and cell motility. 3. Immune cell activities have been shown to be modulated by the dynamic balance between ceramide, sphingosine and S1P, conceptualized as a rheostat. Cell proliferation, differentiation, motility and survival have been attributed to the regulatory actions of S1P. The properties of SPHK activity in immune cells are linked to the functions of triggered growth and survival factors, phorbol esters, hormones, cytokines and chemokines, as well as antigen receptors, such as FcgammaRI and FcepsilonRI. 4. Mechanisms of the SPHK signalling pathway are explored as new targets for drug development to suppress inflammation and other pathological conditions.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"32 3","pages":"153-61"},"PeriodicalIF":0.0,"publicationDate":"2005-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.2005.04166.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24984706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}