Carcinoid tumor detected in gastric adenoma during long-term follow-up.
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Adenocarcinoma↗
Biomedical subjects
Y Kawakami
Publications and source records attributed to Y Kawakami.
Suppression of CYP3A2 mRNA expression in the warfarin-resistant roof rat, Rattus rattus: possible involvement of cytochrome P450 in the warfarin resistance mechanism.
1. The continual use of warfarin as a rodenticide has caused the development of populations of warfarin-resistant roof rat. To study the biochemical mechanism of warfarin resistance, the mRNA expression levels of the major P450 forms in the warfarin-resistant and -susceptible roof rat liver following exposure to warfarin were quantified by competitive RT-PCR. 2. The constitutive levels of CYP2C11 and CYP3A2 mRNAs in the warfarin-resistant and -susceptible roof rat were extremely low compared with those in the STD rat. In response to warfarin administration, the CYP3A2 mRNA level in the warfarin-susceptible rat increased to about 3-fold of that before the treatment, whereas in the warfarin-resistant roof rat, CYP3A2 mRNA remained at a low level. 3. The present results suggest the possibility that reduced synthesis of CYP3A2 mRNA is involved in the warfarin-resistant mechanism in the roof rat.
Animals↗
Angiotensin subtype-2 receptor (AT2 ) negatively regulates subtype-1 receptor (AT1 ) in signal transduction pathways in cultured porcine adrenal medullary chromaffin cells.
BACKGROUND: Two distinct types of angiotensin II (AngII) receptors, AT1 and AT2, have been cloned. We have shown previously that stimulation of AT2 reduces intracellular cyclic guanosine monophosphate (cGMP) levels in cultured porcine chromaffin cells in which AT2 is the predominantly expressed receptor. However, it has not been determined whether AT1 or AT2 affects signal transduction pathways involving mitogen-activated protein kinases (MAPKs) and signal transducers and activators of transcription (STATs) in chromaffin cells. Also, it is unclear whether cGMP/protein kinase G (PKG) is involved in the regulation of MAPKs and STATs in these cells. DESIGN: Chromaffin cells were derived from porcine adrenal medulla. The effects of AngII alone (representing physiological conditions), AngII plus CV-11974 (an AT1 antagonist, which simulates specific AT2 stimulation), AngII plus PD 123319 (an AT2 antagonist, which simulates specific AT1 stimulation), and 8-Br-cGMP (a membrane-permeable cGMP analogue) alone on MAPKs (ERKs, JNK, p-38 MAPK) and STATs (STATs 1, 3 and 5) activity were measured. METHODS: Phosphorylated MAPKs (extracellular signal-related kinases (ERKs), c-jun N-terminal kinase (JNK) and p38 MAPK) and STATs (STATs 1, 3 and 5) were measured by immunoprecipitation-Western blot analysis (IP-Western blot). RESULTS: AT1 stimulation markedly increased expression of ERKs, JNK, p38 MAPK via Ca2+-dependent protein kinase C (PKC) isoforms (cPKC), as well as STATs 1, 3 and 5 in cultured porcine chromaffin cells. In contrast, AT2 stimulation markedly decreased the expression of these signaling molecules. Also, 8-Br-cGMP alone induced increases in ERKs, JNK, p38 MAPK, and STATs 1, 3 and 5. Because AT2 inhibits cGMP production, we speculate that AT2 may act to suppress cGMP production, which in turn reduces the activity of both MAPKs and STATs in chromaffin cells. CONCLUSION: AT2 negatively regulates AT1 in signal transduction pathways in chromaffin cells.
Angiotensin II↗
Successful subcutaneous pancreatic islet transplantation using an angiogenic growth factor-releasing device.
INTRODUCTION: Although the subcutaneous tissue is considered as an attractive site for pancreatic islet transplantation, the success rate has been extremely low. AIMS: To use basic fibroblast growth factor (bFGF) to induce neovascularization and sufficient blood flow around the space formed for grafted islets in the subcutaneous tissue to improve the islet survival. METHODOLOGY: In the experimental group, two bFGF-releasing devices were implanted bilaterally into the subcutaneous tissue (back) of diabetic Lewis rats. One week after implantation, in the same site, isolated rat islets were syngeneically transplanted after the removal of the devices. In the control group, two devices without bFGF were implanted before subcutaneous islet transplantation of the same number of islets. RESULTS: One week after the implantation of the bFGF-releasing devices in the experimental animals, the devices induced angiogenesis by slow release of bFGF. After transplantation of islets, the neovascularized recipient rats showed significant decreases in nonfasting blood glucose concentration and maintained normoglycemia for more than 3 months. However, in the control group, all rats failed to achieve normoglycemia after transplantation in the absence of neovascularization. CONCLUSION: This study provides evidence that the subcutaneous tissue is a promising site for pancreatic islet transplantation, which suggests the acceptability of this treatment for diabetic recipients.
Animals↗
Increased apoptosis associated with depressed type of early intestinal gastric cancer.
Early gastric cancer can be macroscopically classified into elevated and depressed types. To clarify the relationship between macroscopic appearance of early gastric cancer and apoptosis or cell proliferation, formalin-fixed paraffin-embedded tissue specimens of 44 intestinal-type early gastric cancers were investigated by the TUNEL method and immunohistochemical techniques. Diffuse type was excluded in this study. When tissue sections of gastric cancer were vertically classified into the 3 compartments of luminar, intermediate and basal, the apoptosis index (%) was significantly higher in the basal compartment of depressed type (1.76 +/- 2.04, mean +/- SD) than in the basal compartment of elevated type (0.63 +/- 0.81, P = 0.01). In depressed type, the apoptosis index (%) was significantly higher in the basal compartment than in the luminar compartment (0.76 +/- 0.85, P = 0.03). Apoptosis-inducing protein, Bax, was expressed more in each of the compartments of depressed type than in those of elevated type, while there were no significant differences in expression of anti-apoptotic protein, Bcl-2, between the two types. Moreover, the apoptosis index (%) of Bax-positive gastric cancer was significantly higher in the basal compartment (P = 0.03), compared to that of Bax-negative gastric cancer, while there were no significant differences in apoptosis index (%) in any compartment between Bcl-2-positive and Bcl-2-negative gastric cancers. There were no significant differences in Ki-67 expression, either between the two types, or among the compartments of depressed type. These results indicate that increased apoptosis with excessive expression of Bax in the basal compartment is involved in the morphogenesis of the depressed type in intestinal-type early gastric cancer.
Aged↗
Serum angiotensin I-converting enzyme is reduced in Crohn's disease and ulcerative colitis irrespective of genotype.
OBJECTIVES: Crohn's disease (CD) is recognized to be a vascular endothelial-associated disease. Angiotensin I-converting enzyme (ACE) exists mainly in endothelial cells. There are some reports on serum ACE levels in patients with CD, but the ACE level is still controversial. Recently, genetic control of serum ACE levels by ACE gene polymorphisms (classified as II, ID, and DD) has been suggested. Although we must consider such polymorphisms to elucidate ACE levels in patients with CD, there is no report about this. METHODS: We studied 341 healthy controls (male/female = 178/162), 39 patients with CD (31/8), 43 patients with ulcerative colitis (UC) (22/21) and 19 patients with infectious enterocolitis (8/11). The polymorphism in intron 16 of the ACE gene was examined by PCR. Serum ACE levels were measured by the method of Kasahara. RESULTS: Serum ACE levels in patients with CD and UC were significantly lower than in healthy controls, irrespective of the genotype of ACE (genotype II: CD 7.0+/-2.5 [mean +/- SD], UC 7.1+/-3.3, controls 11.8+/-2.9, genotype ID: CD 9.7+/-4.1, UC 11.4+/-4.6, controls 15.2+/-3.6, genotype DD: CD 13.9+/-5.8, UC 10.7+/-3.6, controls 19.3+/-3.9 IU/L, controls vs CD, UC; p < 0.01, 0.05). However, there was no significant difference in serum ACE levels between CD and UC. CONCLUSIONS: Considering ACE gene polymorphism, serum ACE levels in patients with inflammatory bowel disease are lower than in controls. Serum ACE levels reflect a part of the pathogenesis of inflammatory bowel disease.
Adult↗
[A case of bacterial peritonitis caused by Neisseria gonorrhoeae].
On January 17, 2001, a 39-year old female with sudden abdominal pain was admitted to her neighboring outpatient clinic and diagnosed as suspicious of infectious enteritis. However, on the next day (January 18, 2001) she was soon transferred to Toyoshina Red Cross Hospital with the chief complaint of severe abdominal pain, high fever, and of conspicuous leucocytosis. Laboratory data on her admission demonstrated apparent signs of inflammation and she was soon undergone an emergency operation. Neisseria gonorrhoeae was recovered from her ascetic fluid, otherwise Chlamydia EIA was negative. The antibiotic chemotherapy of minocycline (200 mg/day) was continued for the first 9 days and sulbactam/cefoperazone (2 g/day) had been administered for the first 5 days. Her symptoms were discontinued on her 10th hospital day, and she was discharged on the 14th hospital day. There have been few reported cases in Japan of bacterial peritonitis due to N. gonorrhoeae. This is, to the best of our knowledge, the first reported case of N. gonorrhoeae peritonitis in Japan.
Adult↗
Lack of evidence for an increased microchimerism in the circulation of patients with Sjögren's syndrome.
OBJECTIVE: To examine the hypothesis that fetal microchimerism plays a part in the pathogenic process of Sjögren's syndrome (SS). METHODS: Genomic DNA samples were extracted from peripheral blood whole nucleated cells and the CD34+ cell enriched fraction of patients with SS and healthy women who had male offspring as well as nulliparous women. A Y chromosome-specific sequence was detected as a marker for fetal cells by a nested polymerase chain reaction (PCR) and by DNA hybridisation combined with PCR using specific primers and probes. All procedures were performed with great care to avoid the contamination of male DNA. RESULTS: A nested PCR and DNA hybridisation combined with PCR was established that can detect a single male cell out of 1.67x10(5) female cells. It was not possible to increase the sensitivity further because the amount of template DNA held in the PCR was limited. When these methods were used, no fetal cells were detected in any samples from patients with SS, though they were detected in whole nucleated cells from two healthy women who had delivered sons previously. CONCLUSIONS: The findings indicate that circulating fetal cells in patients with SS are uncommon (<1 in 1.67x10(5)), if they exist. With the conventional PCR based methods that were used, it is difficult to evaluate the quantitative difference in circulating fetal cells between patients with SS and healthy women.
Adult↗
Enhancement of goblet cell hyperplasia and airway hyperresponsiveness by salbutamol in a rat model of atopic asthma.
BACKGROUND: Goblet cell hyperplasia (GCH) is a prominent feature in animal models of atopic asthma produced by immunisation and following multiple challenges with antigens. The aim of this study was to examine the effect of a beta(2) agonist on the development of GCH induced by the immune response. METHODS: Brown Norway rats were immunised and challenged with an aerosol of ovalbumin for four weeks. Salbutamol (0.5 mg/kg/day) or vehicle was continuously delivered for the four weeks using a subcutaneously implanted osmotic minipump. The density of goblet cells, other morphological changes, and airway responsiveness to methacholine were evaluated 24 hours after the final challenge. RESULTS: Treatment with salbutamol induced a more than twofold increase in the mean (SE) number of goblet cells (53.7 (7.3) vs 114.5 (11.8) cells/10(3) epithelial cells, p<0.01) while it did not significantly influence airway wall thickening and eosinophilic infiltration. Airway responsiveness to methacholine expressed as the logarithmic value of the concentration of methacholine required to generate a 50% increase in airway pressure (logPC(150)Mch) was also enhanced by the beta(2) agonist (-0.56 (0. 21) vs -0.95 (0.05), p<0.05). Additional experiments revealed that the same dose of the beta(2) agonist alone did not cause GCH in non-immunised rats and that the enhancement of GCH by salbutamol was completely abolished by simultaneous treatment with methylprednisolone (0.5 mg/kg/day). CONCLUSIONS: These data suggest that salbutamol enhances goblet cell hyperplasia and airway hyperresponsiveness in this rat model of atopic asthma.
Adrenergic beta-Agonists↗
Influence of static stretching on viscoelastic properties of human tendon structures in vivo.
The purpose of this study was to investigate the influences of static stretching on the viscoelastic properties of human tendon structures in vivo. Seven male subjects performed static stretching in which the ankle was passively flexed to 35 degrees of dorsiflexion and remained stationary for 10 min. Before and after the stretching, the elongation of the tendon and aponeurosis of medial gastrocnemius muscle (MG) was directly measured by ultrasonography while the subjects performed ramp isometric plantar flexion up to the maximum voluntary contraction (MVC), followed by a ramp relaxation. The relationship between the estimated muscle force (Fm) of MG and tendon elongation (L) during the ascending phase was fitted to a linear regression, the slope of which was defined as stiffness of the tendon structures. The percentage of the area within the Fm-L loop to the area beneath the curve during the ascending phase was calculated as an index representing hysteresis. Stretching produced no significant change in MVC but significantly decreased stiffness and hysteresis from 22.9 +/- 5.8 to 20.6 +/- 4.6 N/mm and from 20.6 +/- 8.8 to 13.5 +/- 7.6%, respectively. The present results suggest that stretching decreased the viscosity of tendon structures but increased the elasticity.
Adult↗
Mechanical properties of tendon and aponeurosis of human gastrocnemius muscle in vivo.
Load-strain characteristics of tendinous tissues (Achilles tendon and aponeurosis) were determined in vivo for human medial gastrocnemius (MG) muscle. Seven male subjects exerted isometric plantar flexion torque while the elongation of tendinous tissues of MG was determined from the tendinous movements by using ultrasonography. The maximal strain of the Achilles tendon and aponeurosis, estimated separately from the elongation data, was 5.1 +/- 1.1 and 5.9 +/- 1.6%, respectively. There was no significant difference in strain between the Achilles tendon and aponeurosis. In addition, no significant difference in strain was observed between the proximal and distal regions of the aponeurosis. The results indicate that tendinous tissues of the MG are homogeneously stretched along their lengths by muscle contraction, which has functional implications for the operation of the human MG muscle-tendon unit in vivo.
Achilles Tendon↗
Influences of repetitive muscle contractions with different modes on tendon elasticity in vivo.
The present study aimed to investigate the effects of repetitive muscle contractions on the elasticity of human tendon structures in vivo. Before and after each endurance test, the elongation of the tendon and aponeurosis of vastus lateralis muscle (L) was directly measured by ultrasonography while the subjects performed ramp isometric knee extension up to maximal voluntary isometric contraction (MVC). Six male subjects performed muscle endurance tests that consisted of knee extension tasks with four different contraction modes: 1) 50 repetitions of maximal voluntary eccentric action for 3 s with 3 s of relaxation (ET1), 2) three sets of 50 repetitions of MVC for 1 s with 3 s of relaxation (ET2), 3) 50 repetitions of MVC for 3 s with 3 s of relaxation (ET3), and 4) 50 repetitions of 50% MVC for 6 s with 6 s of relaxation (ET4). In ET1 and ET2, there were no significant differences in L values at any force production levels between before and after endurance tests. In the cases of ET3 and ET4, however, the extent of elongation after the completion of the tests tended to be greater. The L values above 330 N in ET3 and 440 N in ET4, respectively, were significantly greater after endurance tests than before. These results suggested that the repeated longer duration contractions would make the tendon structures more compliant and that the changes in the elasticity might be not be affected by either muscle action mode or force production level but by the duration of action.
Adult↗
Muscle fiber and tendon length changes in the human vastus lateralis during slow pedaling.
Muscle fascicle lengths of vastus lateralis (VL) muscle were measured in five healthy men during slow pedaling to investigate the interaction between muscle fibers and tendon. Subjects cycled at a pedaling rate of 40 rpm (98 W). During exercise, fascicle lengths changed from 91 +/- 7 (SE) to 127 +/- 5 mm. It was suggested that fascicles were on the descending limb of their force-length relationship. The average shortening velocity of fascicle was greater than that of muscle-tendon complex in the first half of the knee extension phase and was less in the second half. The maximum shortening velocity of fascicle in the knee extension phase was less than that of muscle-tendon complex by 22 +/- 9%. These discrepancies in velocities were mainly caused by the elongation of the tendinous tissue. It was suggested that the elasticity of VL tendinous tissue enabled VL fascicles to develop force at closer length to their optimal length and kept the maximum shortening velocity of VL fascicles low during slow pedaling.
Adult↗
A rare case of bronchial glomus tumor.
A 48-year-old man was admitted because of bloody sputum in whom a chest computed tomography (CT) scan and fiberoptic bronchoscopy demonstrated a polypoid tumor in the left main bronchus. The tumor was surgically resected, and the pathological and immunohistochemical findings led to diagnosis of the tumor as a bronchial glomus tumor.
Biopsy, Needle↗
Ca(2+) mobilization, tyrosine hydroxylase activity, and signaling mechanisms in cultured porcine adrenal medullary chromaffin cells: effects of leptin.
Leptin acts as a satiety factor, but there is also evidence that it affects energy expenditure. Leptin's effects are mediated by its receptors, which function as activators of a Janus family of tyrosine kinases-signal transducer and activator of transcription (JAK-STAT) pathway. We have previously shown that murine recombinant leptin markedly induces both the release of catecholamine and tyrosine hydroxylase (TH) (rate-limiting enzyme in the biosynthesis of catecholamine)-messenger RNA (mRNA) levels, probably through Ob-Rb expressed in cultured porcine chromaffin cells. In the present study, we examined the effect of leptin on Ca(2+) mobilization, TH enzyme activity, and signaling. Ca(2+) channel blockers, nicardipine and omega-Conotoxin GVIA, each at 1 microM, were effective in inhibiting leptin-induced catecholamine secretion. When intracellular Ca(2+) ([Ca(2+)](i)) was measured in fura 2-loaded chromaffin cells, leptin was found to cause a sustained increase of Ca(2+) by mobilizing Ca(2+) from both extra- and intracellular pools. Additionally, leptin significantly stimulated inositol 1.4.5-triphosphate IP(3) production in a dose-dependent manner. TH-activity is regulated by both TH enzyme activity and increased TH-mRNA levels accompanied by increased TH protein synthesis. Leptin (>/=1 nM) significantly stimulated TH enzyme activity and increased the TH protein level, indicating that it stimulates catecholamine biosynthesis. In addition, removal of external Ca(2+) completely inhibited leptin (100 nM)-induced TH enzyme activity. Leptin (>/=1 nM) caused an increase in the activity of mitogen-activated protein kinases (MAPKs) that was accompanied by increased phosphorylation of STAT-3 and -5, but not STAT-1. Moreover, MAPK activity evoked by leptin(100 nM) and TH-mRNA caused by leptin (10 nM) were inhibited by 50 and 30 microM of PD-98059 (the MAP kinase kinase-1 inhibitor), respectively. These findings indicate that leptin activates voltage-dependent Ca(2+) channels (VDCC), presumably L-type and N-type Ca(2+) channels, as well as phospholipase C, and suggest that leptin-induced catecholamine secretion is mainly mediated by activation of VDCC. In addition, leptin stimulates the JAK-STAT pathway as well as increasing the levels of TH-mRNA levels through the MAPK pathway in porcine chromaffin cells.
Adrenal Medulla↗
Leptin stimulates catecholamine synthesis in a PKC-dependent manner in cultured porcine adrenal medullary chromaffin cells.
We have previously shown that murine recombinant leptin directly stimulates catecholamine synthesis through the long form of the leptin receptor (Ob-Rb) expressed in cultured porcine chromaffin cells. Additionally, we found that leptin activates IP3 production after PLC activation. It is well established that activation of PLC elicits IP3 production as well as an increase in diacylglycerol, a compound that stimulates PKC. Therefore, we investigated the involvement of PKC in leptin-induced catecholamine synthesis. Leptin was found to induce significant increases in PKC activity in a dose-dependent manner (1, 10, and 100 nM); chelation of extracellular Ca(2+) by EDTA abolished this PKC stimulatory activity. We also confirmed by Western blot analysis that leptin (at 100 nM) induced significant increases in Ca(2+)-dependent PKC alpha, -beta(I), and -gamma expression. The activity of the rate-limiting enzyme tyrosine hydroxylase (TH) in the biosynthesis of catecholamine is regulated at the transcriptional and posttranscriptional levels. TH enzyme activity and TH mRNA levels induced by 100 nM leptin were significantly inhibited by the PKC inhibitor Ro 32-0432 as well as by EDTA. In addition, increases in TH protein and intracellular catecholamine content stimulated by leptin were completely inhibited by Ro 32-0432. Leptin markedly activated ERKs and, to a lesser extent, JNK; these stimulatory effects on ERKs and JNK were completely inhibited by Ro 32-0432 as well as EDTA. In contrast, leptin did not activate P38 MAPK. Similar to leptin, PMA activated ERK and JNK. Nicardipine and omega-conotoxin GVIA, each at 1 microM, were effective at inhibiting leptin-induced TH enzyme activity, TH mRNA accumulation, PKC activity, and ERK activity. Leptin increased activating protein-1 DNA-binding activity, and this was diminished by Ro 32-0432 as well as EDTA, similar to the reduction of TH mRNA levels. In addition, using supershift analysis, we documented the involvement of c-Fos and, to a lesser extent, c-Jun in leptin-induced activating protein-1 activity. These results indicate that leptin stimulates Ca(2+)-dependent PKC isoform-dependent catecholamine synthesis in porcine chromaffin cells. Previously, we had shown that leptin stimulated cAMP. The present study also showed that H89 (a PKA inhibitor) moderately, but significantly, inhibited leptin-induced ERK and TH mRNA. Consistent with this finding, leptin is shown here to activate novel PKC epsilon, which is assumed to stimulate Raf, upstream of ERKs, via cAMP, supporting the suggestion that Ca(2+)-independent novel PKC may also play some physiological role in regulating catecholamine synthesis.
Adrenal Medulla↗
Activation of angiotensin II subtype 2 receptor induces catecholamine release in an extracellular Ca(2+)-dependent manner through a decrease of cyclic guanosine 3',5'-monophosphate production in cultured porcine adrenal medullary chromaffin Cells.
We have previously demonstrated that CGP 42112 (AT(2) agonist > or =1 nM) markedly reduces catecholamine biosynthesis through AT(2), which is the major angiotensin II (AngII) receptor subtype in cultured porcine chromaffin cells. Also, we have shown that CGP 42112 (> or =1 nM) induces a reduction in cGMP production in these cells. The present study showed that AngII reduced cGMP production via AT(2) in a manner similar to that found with CGP 42112. AngII (1 nM) significantly increased catecholamine secretion from cultured porcine adrenal medullary chromaffin cells. The stimulation was significantly inhibited by PD 123319 (AT(2) antagonist). The stimulation was moderately, but significantly, attenuated by CV-11974 (AT(1) antagonist, > or =10 nM), suggesting an involvement of AT(1). Moreover, CGP 42112 (> or =10 nM) markedly increased catecholamine release from these cells. The stimulation by CGP 42112 was abolished by PD 123319, whereas CV-11974 had no effect, indicating that this response is also mediated by AT(2). We further examined whether extracellular Ca(2+) is involved in the stimulatory effect of AT(2) on catecholamine secretion. Removal of external Ca(2+) significantly suppressed either AngII plus CV-11974 (100 nM; which simulates specific AT(2) stimulation) or CGP 42112- induced catecholamine secretion. AngII plus CV-11974 or CGP 42112 caused a sustained increase in intracellular Ca(2+) ([Ca(2+)](i)), as determined in fura-2-loaded chromaffin cells in an extracellular Ca(2+)-dependent manner. In the presence of EGTA, the subsequent addition of AngII with CV-11974 and CGP 42112 did not cause any increase in [Ca(2+)](i) levels. Consistent with this finding, CGP 42112 (10 nM to 1 microM) did not alter inositol triphosphate (IP(3)) production, a messenger for mobilization of Ca(2+) from intracellular storage sites. In addition, the intracellular Ca(2+) chelator 1,2-bis(2-amino-phenoxy)ethane-N,N,N',N'- tetraacetic acid acetoxymethylester (BAPTA) did not affect CGP 42112-induced catecholamine release. We tested whether a decrease in cGMP was the cause of the stimulatory effect of AT(2) on catecholamine secretion. Pretreatment with 8-bromo-cGMP (1 mM) prevented the stimulatory effect of AngII plus CV-11974 and CGP 42112 on both catecholamine secretion and [Ca(2+)](i). When 8-bromo-cGMP was added after application of AngII plus CV-11974 or CGP 42112, [Ca(2+)](i) induced by these agents was gradually reduced toward the baseline values. Similarly, guanylin completely abolished the AngII- plus CV-11974-induced increase in both NE secretion and [Ca(2+)](i). The Ca(2+) channel blockers, nicardipine and omega-conotoxin G VIA, at 1 microM in both cases, were also effective in inhibiting AT(2) stimulation-induced secretion. On the other hand, neither T-type voltage-dependent Ca(2+) channel blockers, flunarizine, nor Ni(2+) affected catecholamine release caused by AT(2) stimulation. These findings demonstrate that AT(2) stimulation induces catecholamine secretion by mobilizing Ca(2+) through voltage-dependent Ca(2+) channels without affecting intracellular pools and that these effects could be mediated by a decrease in cGMP production.
Adrenal Medulla↗
Wnt signaling and PKA control Nodal expression and left-right determination in the chick embryo.
Expression of the Nodal gene, which encodes a member of the TGFbeta superfamily of secreted factors, localizes to the left side of the developing embryo in all vertebrates examined so far. This asymmetric pattern correlates with normal development of the left-right axis. We now show that the Wnt and PKA signaling pathways control left-right determination in the chick embryo through Nodal. A Wnt/beta-catenin pathway controls Nodal expression in and around Hensen's node, without affecting the upstream regulators Sonic hedgehog, Car and Fibroblast Growth Factor 8. Transcription of Nodal is also positively regulated by a protein kinase A-dependent pathway. Both the adhesion protein N-cadherin and PKI (an endogenous protein kinase A inhibitor) are localized to the right side of the node and may contribute to restrict Nodal activation by Wnt signaling and PKA to the left side of the node.
Alkaline Phosphatase↗