Identification of Second Messenger Pathways Involved in the Cooperative Effects of Ovine GDF9 & BMP15 Stimulated Thymidine Uptake by Rat Granulosa Cells.

2008 ◽  
Vol 78 (Suppl_1) ◽  
pp. 170-171 ◽  
Author(s):  
Jennifer L. Juengel ◽  
Derek A. Heath ◽  
Stan Lun ◽  
Kenneth P. McNatty
Keyword(s):  
Granulosa Cells ◽  
Second Messenger ◽  
Thymidine Uptake ◽  
Cooperative Effects ◽  
Second Messenger Pathways

272. Signalling pathways involved in mouse GDF9 and BMP15 stimulated thymidine uptake by rat granulosa cells

2008 ◽  
Vol 20 (9) ◽  
pp. 72
Author(s):  
K. L. Reader ◽  
C. J. McIntosh ◽  
J. L. Juengel
Keyword(s):  
P38 Mapk ◽  
Granulosa Cells ◽  
Molecular Mechanisms ◽  
Thymidine Incorporation ◽  
Fold Increase ◽  
Fertility Control ◽  
Mitogen Activated Protein Kinase ◽  
Thymidine Uptake ◽  
Cooperative Effects ◽  
Mitogen Activated Protein

The oocyte-secreted factors growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are essential for ovarian follicular growth and development. Understanding the molecular mechanisms of these factors could assist with the development of future products for fertility control. Thymidine uptake by rat granulosa cells is stimulated cooperatively by GDF9 and BMP15. Inhibitors of the activin receptor-like kinase (ALK) 4,5,7 and the nuclear factor kappaB (NFKB) second messenger pathways block ovine GDF9 and BMP15 stimulated thymidine incorporation. The ALK 4,5,7 receptor pathway is known to be essential for the cooperative effects of mouse (m)GDF9 and mBMP15 on thymidine incorporation but the role of other pathways has yet to be determined, which was the focus of this study. Inhibitors of NFKB (Sn50; 10µg/mL), ALK 2,3,6 receptor (Dorsomorphin; 1µM), p38 mitogen-activated protein kinase (p38 MAPK; SB239063; 5 µM) and c-Jun-N-terminal kinase (JNK; TAT-TI-JIP153–163; 5 µM) pathways were each cultured with recombinant mGDF9 (25 ng/mL) and mBMP15 (6 ng/mL) in a rat granulosa cell [3H]-thymidine bioassay. The p38 MAPK inhibitor caused partial inhibition of thymidine uptake but this appeared to be non-specific as a similar level of suppression was observed in the control cultures. Neither the ALK 2,3,6 receptor nor the NFKB pathway inhibitors had any effect on mGDF9 and mBMP15 stimulated thymidine uptake. The JNK inhibitor showed a 1.7-fold increase in stimulation above the mGDF9 and mBMP15 effect (P < 0.01) but a similar stimulation was also observed in some controls. This differs from the results observed with ovine GDF9 and BMP15 where thymidine uptake was completely blocked by the NFKB inhibitor and the JNK inhibitor had no effect. In conclusion, the molecular mechanisms of GDF9 and BMP15 function are dependent on the species of origin of the growth factor and therefore caution is needed when extrapolating findings from one species to another.

scholarly journals Signalling pathways involved in the cooperative effects of ovine and murine GDF9+BMP15-stimulated thymidine uptake by rat granulosa cells

Reproduction ◽  
2011 ◽  
Vol 142 (1) ◽  
pp. 123-131 ◽  
Author(s):  
Karen L Reader ◽  
Derek A Heath ◽  
Stan Lun ◽  
C Joy McIntosh ◽  
Andrea H Western ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Kinase Inhibitor ◽  
Mapk Pathway ◽  
Molecular Complexes ◽  
Nuclear Factor Κb ◽  
Mitogen Activated Protein Kinase ◽  
Molecular Forms ◽  
Signalling Pathways ◽  
Thymidine Uptake ◽  
Cooperative Effects

Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are oocyte-secreted factors known to be involved in regulating the proliferation and differentiation of granulosa cells during follicular growth. The aims of this study were to determine the signalling pathways used by recombinant forms of murine and ovine GDF9 and BMP15 in combination (GDF9+BMP15) and the molecular complexes formed by combinations of these factors. Differences in the molecular forms of combinations of murine and ovine GDF9+BMP15 were observed by western blot analysis. Ovine GDF9+BMP15-stimulated 3H-thymidine uptake was completely blocked by SMAD2/3 and nuclear factor-κB pathway inhibitors and partially blocked by a p38-mitogen-activated protein kinase (MAPK) inhibitor. Thymidine uptake by murine GDF9+BMP15 was reduced by the SMAD2/3 and extracellular signal-regulated kinase-MAPK pathway inhibitors and increased after addition of a c-Jun N-terminal kinase inhibitor. Stimulation of 3H-thymidine uptake by GDF9+BMP15 from either species was not affected by the SMAD1/5/8 pathway inhibitor. In conclusion, both murine and ovine GDF9+BMP15-stimulated thymidine incorporation in rat granulosa cells was dependent on the SMAD2/3 signalling pathway but not the SMAD1/5/8 pathway. Divergence in the non-SMAD signalling pathways used by murine and ovine GDF9+BMP15 was also evident and may be due to the differences observed in the molecular complexes formed by these factors. These results are consistent with the hypothesis that the disparate cooperative functions of GDF9 and BMP15 in different species are mediated by divergent non-SMAD signalling pathways.

170: Do Alpha1Adrenoceptors in pig Urethra Demonstrate agonist-Specific Coupling to Distinct Second Messenger Pathways ?

2005 ◽  
Vol 173 (4S) ◽  
pp. 46-46
Author(s):  
Rachael L. Scott ◽  
Christopher Chappie ◽  
Russell Chess-Williams
Keyword(s):  
Second Messenger ◽  
Second Messenger Pathways

scholarly journals Essential Functions of the Transcription Factor Npas4 in Neural Circuit Development, Plasticity, and Diseases

2020 ◽  
Vol 14 ◽  
Author(s):  
Jian Fu ◽  
Ouyang Guo ◽  
Zhihang Zhen ◽  
Junli Zhen
Keyword(s):  
Transcription Factor ◽  
Neural Circuit ◽  
Second Messenger ◽  
Synaptic Activity ◽  
Postsynaptic Potentials ◽  
Calcium Dependent ◽  
Neural Information ◽  
Formation Function ◽  
Second Messenger Pathways ◽  
Circuit Formation

Signaling from the synapse to nucleus is mediated by the integration and propagation of both membrane potential changes (postsynaptic potentials) and intracellular second messenger cascades. The electrical propagation of postsynaptic potentials allows for rapid neural information processing, while propagating second messenger pathways link synaptic activity to the transcription of genes required for neuronal survival and adaptive changes (plasticity) underlying circuit formation and learning. The propagation of activity-induced calcium signals to the cell nucleus is a major synapse-to-nucleus communication pathway. Neuronal PAS domain protein 4 (Npas4) is a recently discovered calcium-dependent transcription factor that regulates the activation of genes involved in the homeostatic regulation of excitatory–inhibitory balance, which is critical for neural circuit formation, function, and ongoing plasticity, as well as for defense against diseases such as epilepsy. Here, we summarize recent findings on the neuroprotective functions of Npas4 and the potential of Npas4 as a therapeutic target for the treatment of acute and chronic diseases of the central nervous system.

scholarly journals Role of cAMP in the Short-Term Modulation of a Neuromuscular System in Aplysia

2000 ◽  
Vol 83 (3) ◽  
pp. 1567-1579 ◽  
Author(s):  
Lyle E. Fox ◽  
Philip E. Lloyd
Keyword(s):  
Motor Neurons ◽  
Second Messenger ◽  
Neuromuscular System ◽  
Short Term ◽  
Pharmacological Agents ◽  
Camp Pathway ◽  
Low Concentrations ◽  
Excitatory Junction Potentials ◽  
Second Messenger Pathways ◽  
Short Term Effects

Neuromuscular synapses in buccal muscle I3a of Aplysia are modulated by the small cardioactive peptide (SCP), a peptide cotransmitter that is intrinsic to the motor neurons, and by serotonin (5-HT) released from modulatory neurons that are extrinsic to the motor circuit. Although the modulation of excitatory junction potentials (EJPs) and contractions by 5-HT and SCP has been studied extensively in this muscle, little is known about the mechanisms that underlie the modulation. 5-HT and SCP, at 1 μM, were found to potently increase the level of cAMP in I3a. Therefore we investigated whether the activation of the cAMP pathway was sufficient to modulate EJPs and contractions. The direct activation of adenylyl cyclase with forskolin increased the level of cAMP, facilitated EJPs, and potentiated contractions. Indeed, the short-term effects of forskolin were very similar to all aspects of the short-term effects of 5-HT and SCP. Membrane-permeable cAMP analogues also mimicked the effects of 5-HT and SCP on EJPs and contractions. However, it seems likely that some effects of 5-HT are also mediated through other second-messenger pathways because low concentrations of 5-HT modulate EJPs and contractions but do not significantly increase cAMP levels in I3a. It is possible that lower concentrations of 5-HT function through receptors linked to protein kinase C (PKC) because phorbol, an activator of PKC, modulated EJPs and contractions without increasing the levels of cAMP. In conclusion, we provide evidence that pharmacological agents that activate the cAMP pathway mimicked most of the effects of 5-HT or SCP and that more than one second-messenger system appears to be involved in the modulation of the I3a neuromuscular system.

Adenylyl Cyclase Activity and Mood Disorders: Preliminary Data in Human Brain Postmortem

CNS Spectrums ◽  
1998 ◽  
Vol 3 (10) ◽  
pp. 70-75
Author(s):  
Lionella Palego ◽  
Annalisa Giromella ◽  
Maria Rosa Mazzoni ◽  
Antonio Giuseppe Naccarato ◽  
Donatella Marazziti
Keyword(s):  
Human Brain ◽  
Adenylyl Cyclase ◽  
Mood Disorders ◽  
Present Article ◽  
Preliminary Data ◽  
Second Messenger ◽  
Cyclase Activity ◽  
Adenylyl Cyclase Activity ◽  
The Past ◽  
Second Messenger Pathways

AbstractDuring the past decade, an increasing interest has been shifted from the study of neuroreceptors to their links with second-messenger pathways. In the present article, we shall briefly review the methodological tools for evaluating adenylyl cyclase activity in several human brain and peripheral models, as well as the studies suggesting its involvement in the pathophysiology of mood disorders. We shall present also some preliminary data obtained in our laboratory providing evidence for the measurement of serotonin-sensitive adenylyl cyclase activity in human brain postmortem.

Bradykinin stimulates airway epithelial Cl- secretion via two second messenger pathways

1990 ◽  
Vol 258 (6) ◽  
pp. L369-L377 ◽  
Author(s):  
J. J. Smith ◽  
J. D. McCann ◽  
M. J. Welsh
Keyword(s):  
Short Circuit ◽  
Second Messengers ◽  
Second Messenger ◽  
Short Circuit Current ◽  
Cytosolic Calcium ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Ussing Chambers ◽  
Cl Secretion ◽  
Second Messenger Pathways

In canine airway epithelial cells, bradykinin increases intracellular concentrations of D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], cytosolic calcium concentration ([Ca2+]c), and adenosine 3',5'-cyclic monophosphate (cAMP). To determine the role of these second messengers in bradykinin-stimulated Cl- secretion, we studied the secretory response to this peptide using canine tracheal monolayers mounted in Ussing chambers. Bradykinin stimulated Cl- secretion [measured as short-circuit current (Isc)] when added to submucosal or mucosal surfaces; however, secretory responses differed substantially. Submucosal addition of bradykinin induced a biphasic increase in secretion; mucosal addition induced a monophasic increase in secretion. Both responses were mediated by B2 receptors. We show that activation of bradykinin receptors can stimulate Cl- secretion in two ways. 1) Bradykinin added to either surface stimulates prostaglandin synthesis and release at the basolateral surface. This leads to activation of prostaglandin E2-sensitive receptors on the basolateral surface that are coupled to cAMP production and an increase in apical membrane Cl- conductance. 2) In addition, bradykinin added to the submucosal surface increases Ins(1,4,5)P3 and [Ca2+]c levels, which enhance basolateral K+ conductance and the electrical driving force for apical Cl- exit. Whereas secretion requires activation of apical Cl- channels, the data show that Cl- secretion can also be modulated by activation of basolateral K+ channels. These data indicate that bradykinin-induced transepithelial Cl- secretion is mediated by two independent, second messenger pathways. These results provide the first evidence for expression of both pathways in a polar fashion in an epithelial monolayer.

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