[High-intensity interval training (HIIT) induces hepatic ketone body production possibly through altering expression of mTORC1, PPARα and FGF21 in mice].

The present study aims to investigate the production of ketone body in the liver of mice after 6 weeks of high-intensity interval training (HIIT) intervention and explore the possible mechanisms. Male C57BL/6J mice (7-week-old) were randomly divided into control and HIIT groups. The control group did not engage in exercise, while the HIIT group underwent a 6-week HIIT (10° slope treadmill exercise). Changes in weight and body composition were recorded, and blood ketone body levels were measured before, immediately after, and 1 h after each HIIT exercise. After 6-week HIIT, the levels of free fatty acids in the liver and serum were detected using reagent kits, and expression levels of regulatory factors and key enzymes of ketone body production in the mouse liver were detected by Western blot and qPCR. The results showed that, the blood ketone body levels in the HIIT group significantly increased immediately after a single HIIT and 1 h after HIIT, compared with that before HIIT. The body weight of the control group gradually increased within 6 weeks, while the HIIT group mice did not show significant weight gain. After 6-week HIIT, compared with the control group, the HIIT group showed decreased body fat ratio, increased lean body weight ratio, and increased free fatty acid levels in liver and serum. Liver carnitine palmitoyl transferase-I (CPT-I), peroxisome proliferator activated receptor α (PPARα), and fibroblast growth factor 21 (FGF21) protein expression levels were up-regulated, whereas mammalian target of rapamycin complex 1 (mTORC1) protein expression level was significantly down-regulated in the HIIT group, compared with those in the control group. These results suggest that HIIT induces hepatic ketone body production through altering mTORC1, PPARα and FGF21 expression in mice.

[Research advances on high-intensity interval training and cognitive function].

High-intensity interval training (HIIT) has proven to be a time-saving and efficient exercise strategy. Compared with traditional aerobic exercise, it can provide similar or even better health benefits. In recent years, a number of studies have suggested that HIIT could be used as a potential exercise rehabilitation therapy to improve cognitive impairment caused by obesity, diabetes, stroke, dementia and other diseases. HIIT may be superior to regular aerobic exercise. This article reviews the recent research progress on HIIT with a focus on its beneficial effect on brain cognitive function and the underlying mechanisms. HIIT may become an effective exercise for the prevention and/or improvement of brain cognitive disorder.

[Aerobic exercise reduces the expression of pyroptosis-related proteins and inflammatory factors in hippocampus of mice with insulin resistance].

The aim of the present study was to observe the expression of pyroptosis- and inflammation-related proteins in the hippocampus of mice with insulin resistance (IR) after aerobic exercise, and to explore the possible mechanism of exercise to improve IR. C57BL/6J male mice of 6 weeks old were randomly fed with normal diet (n = 12) and high-fat diet (HFD) (n = 26) for 12 weeks respectively. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed to determine whether IR occurred in HFD mice. Then the mice were randomly divided into control group (n = 12), IR group (n = 10) and IR + aerobic exercise group (AE, n = 10). Mice in AE group performed a 12-week progressive speed treadmill training after being adapted to the treadmill for one week. After the intervention, the expression of pyroptosis- and inflammation-related proteins in hippocampus was detected by Western blot. The results showed that compared with control group, NFκB, Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), pyroptosis-related proteins like pro-Caspase-1, gasdermin D (GSDMD), GSDMD-N, and inflammatory factors IL-1ß, IL-18 were significantly increased. The inflammasome-related protein NIMA-related kinase 7 (NEK7) and pyroptosis-related protein Caspase-1 showed an increasing trend, but there was no significant difference. Compared with the IR group, progressive speed treadmill training significantly reduced the expression of NFκB, NLRP3, NEK7, ASC, pro-Caspase-1, GSDMD, GSDMD-N, IL-1ß, and IL-18 in the hippocampus of mice with IR. These results suggested 12-week progressive speed treadmill training can significantly reduce the expression of pyroptosis-related proteins and inflammatory factors in the hippocampus of mice with IR, and inhibit pyroptosis.

[Effects of resistance exercise on pyroptosis-related proteins in hippocampus of insulin resistant mice].

Objective: To investigate the changes of pyroptosis-related proteins in the hippocampus of insulin-resistant mice and the regulation of resistance training on pyroptosis-related proteins. Methods: Six-week-old male C57BL/6J mice were randomly divided into control group (C, n=12) and high-fat diet group (HFD, n=26) for normal or high-fat diet for 12 weeks. Subsequently, according to the results of glucose tolerance test (GTT) and insulin tolerance test (ITT), the rats fed with high-fat diet were divided into insulin resistance group (IR, n=10) and resistance exercise group (RT, n=10) as well as to maintain high-fat diet. At the same time, mice in the RT group were subjected to resistance training. After 12 weeks, all mice were sacrificed after anesthesia, brain was removed and hippocampus was exfoliated, and the expressions of pyroptosis-related proteins were detected by Western blot. Results: Compared with the C group, NF-κB, the NLRP3 inflammasome proteins, their downstream pyroptosis-related proteins GSDMD-N and GSDMD as well as inflammation factors IL-1ß and IL-18 in hippocampus of IR group were significantly increased (P＜0.05), and the expression levels of SIRT1 and p-AMPK protein were significantly decreased (P＜0.05). Compared with the IR group, NF-κB, the NLRP3 inflammasome proteins, their downstream pyroptosis-related proteins GSDMD-N and GSDMD as well as inflammation factors IL-1ß and IL-18 in hippocampus of RT group were significantly decreased (P＜0.05), and the expression levels of SIRT1 and p-AMPK protein were significantly increased (P＜0.01). Conclusion: NLRP3 inflammasome in the hippocampus of insulin-resistant mice is activated, which mediates pyroptosis in the hippocampus. Twelve weeks of resistance training can effectively inhibit the activation of NLRP3 inflammasome and decrease pyroptosis and improve inflammation in the hippocampus.

Excessive endoplasmic reticulum stress and decreased neuroplasticity-associated proteins in prefrontal cortex of obese rats and the regulatory effects of aerobic exercise.

Studies have shown high fat diet induced obesity may cause cognition impairment and down-regulation of neuroplasticity-associated proteins, while aerobic exercise could improve that damage. Endoplasmic reticulum stress (ERS) has been reported to play a key role in regulating neuroplasticity-associated proteins expression, folding and post-translational modification in hippocampus of obese rodent models, however, the effects of ERS on neuroplasticity-associated proteins and possible underlying mechanisms in prefrontal cortex are not fully clear. In order to clarify changes of neuroplasticity-associated proteins and ERS in the prefrontal cortex of obese rats, male SD rats were fed on high fat diet for 8 weeks to establish the obese model. Then, 8 weeks of aerobic exercise treadmill intervention was arranged for the obese rats. Results showed that high fat diet induced obesity caused hyperlipidemia, and significantly promoted FATP1 expression in the prefrontal cortex, meanwhile, we found up-regulation of GRP78, p-PERK, p-eIF2α, caspase-12, CHOP, and Bax/Bcl-2, reflecting the activation of ERS and ERS-mediated apoptosis. Moreover, reduced BDNF and SYN was found in obese rats. However, FATP1, GRP78, p-PERK, p-eIF2α, caspase-12, CHOP, and Bax/Bcl-2 expressions were obviously reversed by aerobic exercise intervention. These results suggested that dietary obesity could induce Prefrontal ERS in SD rats and excessive ERS may play a critical role in decreasing the levels of neuroplasticity-associated proteins. Moreover, aerobic exercise could relieve ERS, thus promoted the expression of neuroplasticity-associated proteins.

[Research advances on anti-inflammatory, antioxidant and anti-apoptotic biological effects of methane].

Methane (CH4) is the simplest hydrocarbons and endogenous CH4 has been thought only to be generated by methanogens in the oral cavity and gastrointestinal tract of the mammals. However, recent animal studies have shown that endogenous CH4 can also be generated from choline and its metabolites in the mammals to protect the plasma membrane from reactive oxygen species attack and repair the membrane. In addition, exogenous CH4 can ameliorate the oxidative stress injury of multiple tissues and organs through its anti-inflammatory, antioxidant and anti-apoptosis effects. This paper reviews the recent researches about CH4 synthetic metabolism and biological functions, and highlights its potential of wide application in the prevention and treatment of oxidative stress related diseases and the significance for the development of gas medicine.

The signaling mechanisms of hippocampal endoplasmic reticulum stress affecting neuronal plasticity-related protein levels in high fat diet-induced obese rats and the regulation of aerobic exercise.

High fat diet (HFD)-induced obesity has been shown to reduce the levels of neuronal plasticity-related proteins, specifically brain-derived neurotrophic factor (BDNF) and synaptophysin (SYN), in the hippocampus. However, the underlying mechanisms are not fully clear. Endoplasmic reticulum stress (ERS) has been reported to play a key role in regulating gene expression and protein production by affecting stress signaling pathways and ER functions of protein folding and post-translational modification in peripheral tissues of obese rodent models. Additionally, HFD that is associated with hyperglycemia could induce hippocampal ERS, thus impairing insulin signaling and cognitive health in HFD mice. One goal of this study was to determine whether hyperglycemia and hyperlipidemia could cause hippocampal ERS in HFD-induced obese SD rats, and explore the potential mechanisms of ERS regulating hippocampal BDNF and SYN proteins production. Additionally, although regular aerobic exercise could reduce central inflammation and elevate hippocampal BDNF and SYN levels in obese rats, the regulated mechanisms are poorly understood. Nrf2-HO-1 pathways play roles in anti-ERS, anti-inflammation and anti-apoptosis in peripheral tissues. Therefore, the other goal of this study was to determine whether aerobic exercise could activate Nrf2-HO-1 in hippocampus to alleviate obesity-induced hippocampal ERS, which would lead to increased BDNF and SYN levels. Male SD rats were fed on HFD for 8weeks to establish the obese model. Then, 8weeks of aerobic exercise treadmill intervention was arranged for the obese rats. Results showed that HFD-induced obesity caused hyperglycemia and hyperlipidemia, and significantly promoted hippocampal glucose transporter 3 (GLUT3) and fatty acid transport protein 1 (FATP1) protein expression. These results were associated with the activation of hippocampal ERS and ERS-mediated apoptosis. At the same time, we found that excessive hippocampal ERS not only significantly decreased proBDNF-the precursor of mature BDNF, but also attenuated p38/ERK-CREB signaling pathways and activated NLRP3-IL-1ß pathways in obese rats. These results were associated with reduced BDNF and SYN protein production. However, these adverse changes were obviously reversed by aerobic exercise intervention through activating the Nrf2-HO-1 pathways. These results suggest that dietary obesity could induce hippocampal ERS in male SD rats, and excessive hippocampal ERS plays a critical role in decreasing the levels of BDNF and SYN. Moreover, aerobic exercise could activate hippocampal Nrf2 and HO-1 to relieve ERS and heighten BDNF and SYN production in obese rats.

[Effects of supplement of corn peptides combined with aerobic exercise on lipolysis key enzymes:adipose triglyceride lipase and lipoprotein lipase of obese rats].

OBJECTIVE: To investigate the effects of supplement of corn peptides plus aerobic exercise on fat loss and blood lipid profile in obese rats resulted from high fat diet and the mechanism:the role of adipose triglyceride lipase (ATGL) and lipoprotein lipase (LPL). METHODS: One hundred and fifty male SD rats (4 weeks age) were randomly divided into control group (C, n=15) fed with ordinary diet and obese model group (M, n=135) fed with high fat diet for 8 weeks. Forty obese rats whose body weight increased by 20% of the mean value of con-trol group were selected and randomly divided into 5 groups(n=8):obesity control group, casein group, corn peptides group, exercise group and exercise+corn peptides group. The rats of the latter two groups completed aerobic excise for 4 weeks at speed of 15 m/min and duration of 60 min per time (6 times/week). After 4 weeks of intervention, the bloods of rats were collected and blood lipid profile plasma levels of triglyceride(TG), total cholesterol (TC), high density lipoprotein(HDL), low density lipoprotein(LDL) were detected. The perirenal fat and epididymal fat were collected and weighed, and the protein levels of ATGL in livers and LPL in adipose tissues were detected by Western blot. RESULTS: ①Compared with obesity control group, the body weight and the masses of perirenal fat and epididymal fat in exercise group and corn peptides+exercise group were decreased obviously, with more obvious decrease in the corn peptides+exercise group compared with the exer-cise group. No difference was found in the rats of corn peptides group and casein group. ②Compared with obesity control group, the plasma TG was decreased in exercise group, and the plasma levels of TG and TC were reduced in the rats of corn peptides+exercise group, while they remained unchanged in the rats of corn peptides group and casein group. The plasma levels of HDL and LDL had no significant difference a-mong groups. ③The protein levels of ATGL in livers and LPL in adipose tissues were significantly increased in the rats of exercise group and corn peptides+exercise group, with more obvious in the latter group. No difference was shown in the rats of corn peptides group and casein group compared with obesity control group. CONCLUSIONS: Significant decrease of body weight, perirenal fat and epididymal fat as well as plasma TG, TC were induced by 4-week aerobic exercise or supplement of corn peptides plus exercise, with more obvious effects induced by corn pep-tides plus exercise than exercise, while no effect was induced by corn peptides alone, which may be related to the enhancements of the protein levels of ATGL in livers and LPL in adipose tissues.

WNK1 is involved in Nogo66 inhibition of OPC differentiation.

LINGO-1 is a transmembrane receptor expressed primarily in the central nervous system (CNS) and plays an important role in myelination. Recent studies have indicated that it is also involved in oligodendrocyte precursor cell (OPC) survival and differentiation; however, the downstream signaling pathway underlying OPC development is unknown. In our previous study, we found that LINGO-1 is associated with WNK1 in mediating Nogo-induced neurite extension inhibition by RhoA activation. In an effort to identify the role of LINGO-1-WNK1 in OPCs, we first confirmed that WNK1 is also expressed in OPCs and co-localized with LINGO-1, which suppresses WNK1 expression by RNA interference-attenuated Nogo66-induced inhibition of OPC differentiation. Furthermore, we mapped the WNK1 kinase domain using several fragmented peptides to identify the key region of interaction with LINGO-1. We found that a sequence corresponding to the D6 peptide is necessary for the interaction. Finally, we found that using the TAT-D6 peptide to introduce D6 peptide into primary cultured OPC inhibits the association between LINGO-1 and WNK1 and significantly attenuates Nogo66-induced inhibition of OPC differentiation. Taken together, our results show that WNK1, via a specific region on WNK1 kinase domain, interacts with LINGO-1, thus mediating Nogo66-inhibited OPC differentiation.

[Effects of hypoxia conditioned medium of cerebral cortex cells on the differentiation of neural stem cells and related signal pathways].

The aim of this study was to investigate the effects of hypoxia conditioned medium (HCM) of cerebral cortex cells on the differentiation of neural stem cells (NSCs) and to clarify the signal transduction mechanism. The cerebral cortex cells from newborn SD rats were primarily cultured for 5 d, and then the cells were cultured in environments of 4% O2, 1% O2 and normal oxygen concentration, respectively, for 6 h. The culture mediums were collected and centrifuged as the HCM and normoxia conditioned medium (NCM). The neurospheres of NSCs were obtained from the rat cerebral cortex by suspending culture. Immunohistochemical staining was used after adherence culture for 48 h to identify neurons and astrocytes in the progeny of NSCs. LY294002, a PI3-K inhibitor, and SP600125, a JNK inhibitor, were added into the HCM to culture NSCs for 48 h. The results showed that NSCs in the cerebral cortex could differentiate into ß-Tubulin III immunoreactive neurons and GFAP immunoreactive astrocytes in three conditioned mediums, and the neurons proportion in progeny of NSCs was higher than astrocytes in all three groups. The proportion of neurons in 4% HCM was higher than that in NCM (P < 0.01). But the proportion of neurons in 1% HCM was less than that in NCM (P < 0.01). Both LY294002 and SP600125 inhibited NSCs to differentiate into high proportion neurons induced by 4% HCM (P < 0.01), but the inhibitory effect of LY294002 was stronger than that of SP600125 (P < 0.01). In conclusion, 4% HCM can induce NSCs to differentiate into more neurons mainly through the PI3-K pathway.

A meta-analysis of core stability exercise versus general exercise for chronic low back pain.

OBJECTIVE: To review the effects of core stability exercise or general exercise for patients with chronic low back pain (LBP). SUMMARY OF BACKGROUND DATA: Exercise therapy appears to be effective at decreasing pain and improving function for patients with chronic LBP in practice guidelines. Core stability exercise is becoming increasingly popular for LBP. However, it is currently unknown whether core stability exercise produces more beneficial effects than general exercise in patients with chronic LBP. METHODS: Published articles from 1970 to October 2011 were identified using electronic searches. For this meta-analysis, two reviewers independently selected relevant randomized controlled trials (RCTs) investigating core stability exercise versus general exercise for the treatment of patients with chronic LBP. Data were extracted independently by the same two individuals who selected the studies. RESULTS: From the 28 potentially relevant trials, a total of 5 trials involving 414 participants were included in the current analysis. The pooling revealed that core stability exercise was better than general exercise for reducing pain [mean difference (-1.29); 95% confidence interval (-2.47, -0.11); P = 0.003] and disability [mean difference (-7.14); 95% confidence interval (-11.64, -2.65); P = 0.002] at the time of the short-term follow-up. However, no significant differences were observed between core stability exercise and general exercise in reducing pain at 6 months [mean difference (-0.50); 95% confidence interval (-1.36, 0.36); P = 0.26] and 12 months [mean difference (-0.32); 95% confidence interval (-0.87, 0.23); P = 0.25]. CONCLUSIONS: Compared to general exercise, core stability exercise is more effective in decreasing pain and may improve physical function in patients with chronic LBP in the short term. However, no significant long-term differences in pain severity were observed between patients who engaged in core stability exercise versus those who engaged in general exercise. SYSTEMATIC REVIEW REGISTRATION: http://www.crd.york.ac.uk/PROSPERO PROSPERO registration number: CRD42011001717.

Hippocampal neurogenesis and gene expression depend on exercise intensity in juvenile rats.

Exercise can increase neurogenesis and affect gene expression in the brains of adult rats. Little is known about how exercise intensity affects neurogenesis and associated gene expression in juvenile rats. Here, we show that exercise influenced neurogenesis and mRNA expression of brain derived neurotrophic factor (BDNF), N-methyl-d-aspartate receptor type 1 (NMDAR1), vascular endothelial growth factor (VEGF) and fetal liver kinase-1 (Flk-1) in the hippocampus of 5 weeks old rats in an intensity-dependent manner. One week of low- or moderate-intensity exercise in a treadmill running task enhanced neurogenesis in the dentate gyrus of hippocampus. The low-, but not the high-, intensity exercise paradigm resulted in significantly increased expression of BDNF, NMDAR1, and Flk-1 mRNA. Gene expression levels in the low-intensity exercise group were greater than the high-intensity group for these four molecules.

[Treadmill running enhances the ability of learning in young rats.].

To investigate the effect of treadmill running on the ability of learning in young rats, male Sprague-Dawley rats (5 weeks of age) were used for the experiment. Animals were randomly divided into the control and running groups (n=15 in each group). The rats in running group were made run on a motor-driven treadmill for 1 week at a speed of 2 m/min for the first 5 min, at a speed of 5 m/min for the next 5 min, then at a speed of 8 m/min for the last 20 min. Then the Morris water maze was used to observe learning and memory ability of rats in both groups. The tests consisted of place navigation and spatial probe test. We found that, in place navigation training, the latency of rats in running group was less than that in control group (P<0.05); and from the third training session on, there was significant difference between the rats in control and running groups in swimming velocity (P<0.01); furthermore, it was observed that the rats in running group had stronger motivation and more exact orientation in searching for platform, which could be indicated by the index of turn angle and angular velocity. In spatial probe test, there was no significant difference between the two groups in swimming velocity, percentage of swimming distance and frequency of crossing platform in D quadrant, where the platform situated (P>0.05). These findings suggest that low speed treadmill running can enhance the ability of learning in young rats.

Rapid nongenomic effects of glucocorticoids on allergic asthma reaction in the guinea pig.

Glucocorticoids (GCs) are routinely believed to work solely through genomic mechanisms. Recent evidence indicates that GCs can act at the membrane to exert rapid nongenomic effects on various tissues and cells. To ascertain whether nongenomic effects of GCs exist on the allergic asthma reaction, Hartley guinea pigs were sensitized with ovalbumin and challenged with the same antigen given by aerosol. Some animals received inhaled budesonide (3 mg/ml suspended in Hydroxypropyl methylcellulose vehicle) for 5 minutes before ovalbumin challenge; Other animals received saline or blank vehicle as control. We measured the changes of lung resistance and dynamic lung compliance, the pulmonary function used to evaluate allergic asthma severity. Inhaled budesonide inhibited allergic reaction within 10 minutes, which would preclude genomic-mediated responses that normally takes several hours to occur. This study infers for the first time that rapid nongenomic effect of GCs exists on allergic asthma reaction, and provides a new way to investigate nongenomic mechanism of GCs. Further study would raise the possibility of new therapeutic strategies for allergic disease including asthma.

[Effect of tumor necrosis factor-alpha on differentiation of mesencephalic neural stem cells and proliferation of oligodendrocytes in the rat].

To observe the influence of tumor necrosis factor-alpha (TNF-alpha) on differentiation of rat mesencephalic neural stem cells (NSCs), the numbers of neurons, astrocytes and oligodendrocytes generated from NSCs were analyzed after differentiation for 3 days by using immunocytochemistry technique. The results show that: (1) TNF-alpha enhanced the proportions of neurons and oligodendrocytes in progeny of NSCs; and (2) TNF-alpha induced the proliferation of oligodendrocytes derived from NSCs, but the proliferation of astrocytes was not influenced by TNF-alpha. We conclude that the TNF-alpha could influence the application of NSCs.

The effect of bone marrow stromal cells on neuronal differentiation of mesencephalic neural stem cells in Sprague-Dawley rats.

There are numerous parallels between the heamatolymphopoietic and nervous systems in terms of the mechanisms regulating their development. We proposed that neural stem cells (NSCs) may respond to the microenvironmental signals provided by bone marrow stromal cells (BMSCs) which regulate the differentiation and maturation of hematolymphopoietic stem cells. First, we isolated and proliferated BMSCs from the femur and tibia, and NSCs from the midbrain of Sprague-Dawley (SD) rats, and then investigated the effects of BMSCs on the differentiation of NSCs into neurons, astrocytes and oligodendrocytes by directly plating neurospheres on BMSC monolayers in serum-free conditions. The results confirmed that BMSCs induced NSCs to differentiate selectively into neurons. The percentage of neurons significantly increased in 7 days in vitro co-cultures of NSCs and BMSCs as compared to NSCs cultures alone. When the duration of the cultures was extended to 12 days in vitro, BMSCs enhanced the survival of neurons derived from these NSCs; our investigation then focused on the underlying mechanism for this effect of BMSCs. NSCs were cultured with BMSC conditioned-medium and co-cultured with membrane fragments of live BMSCs or paraformaldehyde fixed BMSCs, the inducing activity of BMSCs was solely detectable in BMSC conditioned-medium, indicating that soluble factors secreted by BMSCs were responsible for its effect on the neuronal differentiation of NSCs. Therefore, BMSCs may provide a powerful tool for therapeutic neurological applications.

[Effects of different frequency electromagnetic fields on the differentiation of midbrain neural stem cells].

Objective. To examine the effect of electromagnetic fields (EMF) (20 Hz, 8 mT; 5 Hz, 8 mT) on the neuron-orientated differentiation of neural stem cells (NSCs) from midbrains of new-bom rats. Method. Differentiated NSCs were exposed to EMF for 2 x 15 min per day lasting for I d, 5 d, or 10 d. The sham-exposure controls were correspondingly established. Cells were fixed and processed for immunofluorescent staining using the antibody against neuron-specific marker MAP2, then the percentage of MAP2+ cells was calculated. Result. The two EMFs promoted the differentiation of a neuronal fate in different ways. Both of them came into effect even after 1 d exposure. When cells exposed to the 20 Hz EMF, the percentage of neuron-orientated cells gradually increased with longer-term exposure and the most significant effect appeared in 10 d group while that happened in 5 d group under the condition of 5 Hz EMF. The effect contrasted horizontally, significant differences between the two EMFs were observed only at 10 d groups, 20 Hz EMF having more favorable effect than 5 Hz EMF. Conclusion. 20 Hz and 5 Hz EMF could promote the differentiation of midbrain NSCs to a neuronal phenotype in different ways, suggesting that the physical induction might be another strategy to manipulate the differentiation of NSCs.

A rapid, nongenomic action of glucocorticoids in rat B103 neuroblastoma cells.

We report here a new example in which glucocorticoids (GCs) acted in a rapid, nongenomic way. In rat B103 neuroblastoma cells, 5-hydroxytryptamine (5-HT) was found to evoke an immediate rise in intracellular free calcium concentration ([Ca(2+)](i)). Pre-incubation of B103 cells for 5 min with corticosterone (B) or bovine serum albumin-conjugated corticosterone (B-BSA) concentration-dependently (10(-4)-10(-8) M) inhibited the peak increments in [Ca(2+)](i). Cortisol and dexamethasone had a similar effect, while deoxycorticosterone and cholesterol were ineffective. This rapid inhibitory effect of corticosterone could be mimicked by protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) and abolished completely by PKC inhibitors Ro31-8220 or GF-109203X. Neither pertussis toxin (PTX) nor nuclear GC receptor (GR) antagonist RU38486 influenced the rapid action of B. Our results suggest that GCs can modulate the 5-HT-induced Ca(2+) response in B103 cells in a membrane-initiated, nongenomic, and PKC-dependent manner.