Penile erection is controlled by adrenergic and nonadrenergic-noncholinergic (NANC) neurotransmission. There are many other substances involved in the corpus cavernosum smooth muscle contraction and relaxation. Among them. histamine is supposed to play an important role to the penile erection mechanisms in both human and animals, but the exact effect and mechanisms are not established. To investigate the effects of histamine on the corpus cavernosum tissue and the intracellular signal transduction mechanisms, we have studied on the rabbit corpus cavernosum using organ bath and the following results were obtained. 1. Corpus cavernosum tissue showed contraction in response to histamine in a dose-dependent manner( ED50 = 2.59 x 0.00001mol). 2. Pheniramine maleate ( 0.00001mol), a H1-receptor antagonist, abolished histamine-induced contraction, but cimetidine(0.00001mol), a H2-receptor antagonist, had no effect on histamine- induced contraction. 3. Histamine-induced contraction was abolished by W-7 (0.0001mol), a calmodulin antagonist, but not affected by staurosporine ( 0.0000001mol), a protein kinase C inhibitor. 4. In the precontracted tissue by phenylephrine histamine produced no relaxation, but pheniramine maleate produced significant relaxation in precontracted tissue It is concluded that in rabbit, histamine induced a dose-dependent contraction mediated by H1- receptors and calcium-calmodulin complex as an intracellular second messenger, but there were few H2-receptors in rabbit corpus cavernosum tissue. By the results of this study, it is supposed that histamine or pheniramine maleate could be used as a drug of intracavernosal injection therapy, but human tissue study, in vivo study and/or in vitro study under electrical stimulation must be preceded.
Animals ; Baths ; Calmodulin ; Electric Stimulation ; Histamine* ; Humans ; Male ; Muscle, Smooth ; Penile Erection ; Pheniramine ; Phenylephrine ; Protein Kinase C ; Relaxation ; Second Messenger Systems ; Signal Transduction ; Staurosporine ; Synaptic Transmission

Mitogen-activated protein kinase (MAPK) cascade system is one of the highly conserved signal systems in eukaryotic cells, which participates in the regulation of many biological processes. Under the stimulation of different signals (such as cytokines, neurotransmitters, and hormones), MAPK cascade activates downstream targets and controls a variety of cellular processes, including growth, immunity, inflammation, and stress response. In different cells, the effects of MAPK cascade on cells vary with the stimuli and the duration of stimulation. MAPK cascade induces Th differentiation and participates in T cell receptor signal pathway and B cell receptor signal pathway. MAPK cascades regulate various cellular activities related to the occurrence and development of cancer. A thorough and systematic understanding of the specific regulatory effects of MAPK cascade on various cellular processes will provide theoretical guidance for treating various diseases.
Humans ; MAP Kinase Signaling System ; Signal Transduction ; Cell Cycle ; Neoplasms ; Inflammation

OBJECTIVE: To investigate the effects of SINC, a secreted protein of Chlamydia psittaci, on autophagy of host cells and the role of MAPK/ERK signaling pathway in mediating SINC-induced autophagy. METHODS: RAW 264.7 cells treated with recombinant SINC were examined for changes in expression levels of LC3-II, Beclin-1, phosphorylated and total ERK1/2 using Western blotting. The expression level of LC3 in the treated cells was detected using immunofluorescence analysis, and the formation of autophagosomes and autolysosomes was observed with transmission electron microscopy (TEM). The effect of pretreatment with U0126 (a specific ERK inhibitor) on the expression levels of LC3-II and Beclin-1 in RAW 264.7 cells exposed to different concentrations of SINC was examined using Western blotting, and LC3 puncta in the cells was detected with immunofluorescence analysis. RESULTS: The expression levels of LC3-II and Beclin-1 were the highest in RAW 264.7 cells treated with 2 μg/mL SINC for 12h. Immunofluorescence analysis showed exposure to SINC significantly increased the number of cells containing LC3 puncta, where the presence of autophagosomes and autolysosomes was detected. Exposure to 2 μg/mL SINC for 15 min resulted in the most significant increase of the ratios of p-ERK1/2/ERK1/2 in RAW 264.7 cells. Pretreatment of the cells with U0126 prior to SINC exposure significantly decreased the ratio of p-ERK1/2/ERK1/2, lowered the expression levels of LC3-II and Beclin-1, and decreased LC3 aggregation in the cells. CONCLUSIONS SINC exposure can induce autophagy in RAW 264.7 cells by activating the MAPK/ERK signaling pathway.
MAP Kinase Signaling System ; Chlamydophila psittaci ; Beclin-1 ; Signal Transduction ; Autophagy

Correlated firings among neurons have been extensively investigated; however, previous studies on retinal ganglion cell (RGC) population activities were mainly based on analyzing the correlated activities between the entire spike trains. In the present study, the correlation properties were explored based on burst-like activities and solitary spikes separately. The results indicate that: (1) burst-like activities were more correlated with other neurons' activities; (2) burst-like spikes correlated with their neighboring neurons represented a smaller receptive field than that of correlated solitary spikes. These results suggest that correlated burst-like spikes should be more efficient in signal transmission, and could encode more detailed spatial information.
Action Potentials ; Animals ; Computer Simulation ; Darkness ; Electrophysiology ; In Vitro Techniques ; Light ; Patch-Clamp Techniques ; Postsynaptic Potential Summation ; Rana catesbeiana ; physiology ; surgery ; Retina ; physiology ; Retinal Ganglion Cells ; physiology ; Retinal Neurons ; physiology ; Signal Transduction

An increase in intracellular Ca2+ is the primary trigger of contraction of gastrointestinal (GI) smooth muscles. However, increasing the Ca2+ sensitivity of the myofilaments by elevating myosin light chain phosphorylation also plays an essential role. Inhibiting myosin light chain phosphatase activity with protein kinase C-potentiated phosphatase inhibitor protein-17 kDa (CPI-17) and myosin phosphatase targeting subunit 1 (MYPT1) phosphorylation is considered to be the primary mechanism underlying myofilament Ca2+ sensitization. The relative importance of Ca2+ sensitization mechanisms to the diverse patterns of GI motility is likely related to the varied functional roles of GI smooth muscles. Increases in CPI-17 and MYPT1 phosphorylation in response to agonist stimulation regulate myosin light chain phosphatase activity in phasic, tonic, and sphincteric GI smooth muscles. Recent evidence suggests that MYPT1 phosphorylation may also contribute to force generation by reorganization of the actin cytoskeleton. The mechanisms responsible for maintaining constitutive CPI-17 and MYPT1 phosphorylation in GI smooth muscles are still largely unknown. The characteristics of the cell-types comprising the neuroeffector junction lead to fundamental differences between the effects of exogenous agonists and endogenous neurotransmitters on Ca2+ sensitization mechanisms. The contribution of various cell-types within the tunica muscularis to the motor responses of GI organs to neurotransmission must be considered when determining the mechanisms by which Ca2+ sensitization pathways are activated. The signaling pathways regulating Ca2+ sensitization may provide novel therapeutic strategies for controlling GI motility. This article will provide an overview of the current understanding of the biochemical basis for the regulation of Ca2+ sensitization, while also discussing the functional importance to different smooth muscles of the GI tract.
Actin Cytoskeleton ; Calcium* ; Gastrointestinal Motility ; Gastrointestinal Tract ; Muscle, Smooth* ; Myofibrils ; Myosin Light Chains ; Myosin-Light-Chain Phosphatase ; Neuroeffector Junction ; Neurotransmitter Agents ; Phosphorylation ; Protein Kinases ; Signal Transduction ; Synaptic Transmission

Toll-like receptors (TLRs) are the archetypal pattern recognition receptors in sensing exogenous pathogens. Activation of TLRs is a first line of defense of the immune system, leading to the activation and recruitment of neutrophils and macrophages to sites of infection and enhances antimicrobial activity. The TLR signaling through different intracellular molecules, such as MAP kinases and IkappaB kinases which are conserved signaling elements for many receptors, leads to a distinct set of proinflammatory gene expressions. However, how these pathways differentially and precisely control the transcription of identical genes remains largely unknown. Our review focuses on the details of up-to- date signaling molecules including negative regulators and their role in controlling innate immune response. We also stress the importance of developing systemic approaches for the global understanding of TLR signaling so that appropriate drug therapeutic targets can be identified for regulating inflammatory diseases.
Adaptor Proteins, Signal Transducing/*immunology ; Animals ; Humans ; MAP Kinase Signaling System/*immunology ; Receptor Cross-Talk ; Receptors, Interleukin-1/immunology ; *Signal Transduction ; Toll-Like Receptors/*immunology

OBJECTIVEPotention drug-targets on anti-neuropathy of stroke were summarized, and it will provide materials for developing innovation components traditional Chinese medicine on anti-cerebral infarction neuropathy.

METHODThis article had done a series of researching work about neurovascular unit which includes three kinds of cells: neuron, gliacyte,brain microvascular endothelial cell, then signal mechanism of cell death or apoptosis of each section of stroke neuropathy was analysised by the historical documents.

RESULTThere are five important pathways: inflammatory factor-MMPs pathway- Caspases, Ca2+ -mitochondrial pathway-Caspases, Ca2+ -Phospholipase-PI-3K/AK pathway, Ca2+ -radical-MAPK pathway, Ca2+ -NO-protease pathway, among all the nodes, Caspases, Ca2+, NO were the most important ones.

CONCLUSIONDeveloping the multi-mechanism and multilevel of traditional chinese medicine under the guidance of the theories of network pharmacology and neurovascular unit will play an important role in studying the key links of signal-network of stroke neuropathy.

Calcium ; metabolism ; Caspases ; metabolism ; Cerebral Infarction ; metabolism ; prevention & control ; Drug Delivery Systems ; methods ; Humans ; MAP Kinase Signaling System ; Matrix Metalloproteinases ; metabolism ; Medicine, Chinese Traditional ; methods ; Models, Biological ; Pharmacology ; methods ; Phosphatidylinositol 3-Kinases ; metabolism ; Polyneuropathies ; metabolism ; prevention & control ; Proto-Oncogene Proteins c-akt ; metabolism ; Signal Transduction

OBJECTIVES: This study aimed to demonstrate the activities and phosphorylation changes induced by acute ethanol treatment and withdrawal conditions in the intracellular signal transduction molecules [such as extracellular signal-regulated kinase (ERK), glycogen synthase kinase 3beta (GSK3beta), and Akt] of the SH-SY5Y neuroblastoma cell line. METHODS: The acute treatment exposed SH-SY5Y cells to 100 mM ethanol, and we took samples 30 minutes, 60 minutes, and 24 hours after initiating this treatment. After 24 hours' continuous ethanol treatment, we initiated ethanol withdrawal, taking samples at 30 minutes and 60 minutes. We assayed the kinase phosphorylations via an immunoblot analysis using phosphorspecific antibodies, quantified by optical densitometry. RESULTS: Ethanol treatment induced a transient increase in phosphorylation of GSK3beta and Akt at 30 minutes but failed to change the phosphorylation level of ERK. Ethanol withdrawal induced a transient ERK phosphorylation increase at 30 minutes, but it had no effect on the phosphorylation of GSK3beta or Akt. CONCLUSION: The results indicate that the ethanol-induced cellular response includes the ERK, GSK3beta, and Akt systems. In particular, the ERK pathway may play a role in the acute withdrawal response. This also suggests that a relatively short exposure to ethanol, such as the 24-hour exposure in this study, can induce functional adaptation within a cell.
Antibodies ; Cell Line ; Densitometry ; Ethanol ; Glycogen Synthase Kinase 3 ; Glycogen Synthase Kinases ; Humans ; MAP Kinase Signaling System ; Neuroblastoma ; Phosphorylation ; Phosphotransferases ; Signal Transduction

The present study was aimed to clarify the signaling molecular mechanism by which fibroblast growth factor 21 (FGF21) regulates leptin gene expression in adipocytes. Differentiated 3T3-F442A adipocytes were used as study object. The mRNA expression level of leptin was detected by fluorescence quantitative RT-PCR. The phosphorylation levels of proteins of signal transduction pathways were detected by Western blot. The results showed that FGF21 significantly down-regulated the mRNA expression level of leptin in adipocytes, and FGF21 receptor inhibitor BGJ-398 could completely block this effect. FGF21 up-regulated the phosphorylation levels of ERK1/2 and AMPK in adipocytes. Either ERK1/2 inhibitor SCH772984 or AMPK inhibitor Compound C could partially block the inhibitory effect of FGF21, and the combined application of these two inhibitors completely blocked the effect of FGF21. Neither PI3K inhibitor LY294002 nor Akt inhibitor AZD5363 affected the inhibitory effect of FGF21 on leptin gene expression. These results suggest that FGF21 may inhibit leptin gene expression by activating ERK1/2 and AMPK signaling pathways in adipocytes.
3T3 Cells ; Adenylate Kinase ; Adipocytes ; metabolism ; Animals ; Down-Regulation ; Fibroblast Growth Factors ; metabolism ; Leptin ; metabolism ; MAP Kinase Signaling System ; Mice ; Phosphorylation ; Signal Transduction

OBJECTIVETo explore the effect of epidermal growth factor-like domain 7(EGFL7) on the migration and angiogenesis of endothelial cells.

METHODSEGFL7 overexpression vectors were constructed and transfected into human microvascular endothelial cells. The expression levels of EGFL7-mRNA and EGFL7 protein were examined by real-time RT-PCR and Western blot. Cell migration was analyzed by the wound healing. The capability of cell to form capillary-like tubes in vitro was evaluated on matrigel assay. Protein expression of p-AKT, AKT, p-ERK and ERK in endothelial cells was detected by Western blot upon transfection with EGFL7 overexpression vectors and vehicle control for 0, 10, 30 and 60 min.

RESULTSMigration and angiogenesis of endothelial cells were notably enhanced by EGFL7 overexpression. ERK pathway was strongly activated by EGFL7, whereas AKT remained constant in endothelial cells. Inhibition of ERK impaired EGFL7 induced ERK activation and endothelial cell migration and angiogenesis.

CONCLUSIONEGFL7 effectively promotes migration and angiogenesis through ERK signaling pathway in endothelial cells.

Blotting, Western ; Cell Movement ; Endothelial Cells ; physiology ; Endothelial Growth Factors ; genetics ; physiology ; Humans ; MAP Kinase Signaling System ; physiology ; Neovascularization, Physiologic ; RNA, Messenger ; metabolism ; Signal Transduction