scholarly journals Adenosine: an activity-dependent axonal signal regulating MAP kinase and proliferation in developing Schwann cells

2004 ◽  
Vol 1 (1) ◽  
pp. 23-34 ◽  
Author(s):  
BETH STEVENS ◽  
TOMOKO ISHIBASHI ◽  
JIANG-FAN CHEN ◽  
R. DOUGLAS FIELDS

Nonsynaptic release of ATP from electrically stimulated dorsal root gangion (DRG) axons inhibits Schwann cell (SC) proliferation and arrests SC development at the premyelinating stage, but the specific types of purinergic receptor(s) and intracellular signaling pathways involved in this form of neuron–glia communication are not known. Recent research shows that adenosine is a neuron–glial transmitter between axons and myelinating glia of the CNS. The present study investigates the possibility that adenosine might have a similar function in communicating between axons and premyelinating SCs. Using a combination of pharmacological and molecular approaches, we found that mouse SCs in culture express functional adenosine receptors and ATP receptors, a far more complex array of purinergic receptors than thought previously. Adenosine, but not ATP, activates ERK/MAPK through stimulation of cAMP-linked A2A adenosine receptors. Both ATP and adenosine inhibit proliferation of SCs induced by platelet-derived growth factor (PDGF), via mechanisms that are partly independent. In contrast to ATP, adenosine failed to inhibit the differentiation of SCs to the O4+ stage. This indicates that, in addition to ATP, adenosine is an activity-dependent signaling molecule between axons and premyelinating Schwann cells, but that electrical activity, acting through adenosine, has opposite effects on the differentiation of myelinating glia in the PNS and CNS.

2009 ◽  
Vol 297 (4) ◽  
pp. R940-R949 ◽  
Author(s):  
Dayane A. Gomes ◽  
Zhilin Song ◽  
Wanida Stevens ◽  
Celia D. Sladek

Coexposure of hypothalamo-neurohypophyseal system explants to ATP and phenylephrine [PE; an α1-adrenergic receptor (α1-AR) agonist] induces an extended elevation in vasopressin and oxytocin (VP/OT) release. New evidence is presented that this extended response is mediated by recruitment of desensitization-resistant ionotropic purinergic receptor subtypes (P2X-Rs): 1) Antagonists of the P2X2/3 and P2X7-Rs truncated the sustained VP/OT release induced by ATP+PE but did not alter the transient response to ATP alone. 2) The P2X2/3 and P2X7-R antagonists did not alter either ATP or ATP+PE-induced increases in [Ca2+]i. 3) P2X2/3 and P2X7-R agonists failed to elevate [Ca2+]i, while ATP-γ-S, an agonist for P2X2-Rs increased [Ca2+]iand induced a transient increase in VP/OT release. 4) A P2Y1-R antagonist did not prevent initiation of the synergistic, sustained stimulation of VP/OT release by ATP+PE but did reduce its duration. Thus, the desensitization-resistant P2X2/3 and P2X7-R subtypes are required for the sustained, synergistic hormone response to ATP+PE, while P2X2-Rs are responsible for the initial activation of Ca2+-influx by ATP and ATP stimulation of VP/OT release. Immunohistochemistry, coimmunoprecipitation, and Western blot analysis confirmed the presence of P2X2 and P2X3, P2X2/3, and P2X7-R protein, respectively in SON. These findings support the hypothesis that concurrent activation of P2X2-R and α1-AR induces calcium-driven recruitment of P2X2/3 and 7-Rs, allowing sustained activation of a homeostatic circuit. Recruitment of these receptors may provide sustained release of VP during dehydration and may be important for preventing hemorrhagic and septic shock.


2003 ◽  
Vol 83 (3) ◽  
pp. 357-364 ◽  
Author(s):  
T. A. Davis ◽  
A. Suryawan ◽  
J. A. Bush ◽  
P. M. J. O’Connor ◽  
M. C. Thivierge

Young animals utilize their dietary amino acids more efficiently for growth because they are capable of a greater increase in tissue protein synthesis in response to feeding than older animals. This response to feeding is particularly profound in skeletal muscle. The feeding-induced stimulation of protein synthesis in skeletal muscle is uniquely and independently regulated by both insulin and amino acids. In most visceral tissues, the stimulation of protein synthesis by feeding is mediated by amino acids alone and not by insulin. The stimulation of protein synthesis by nutrition and hormones is regulated by alterations in the expression and activity of components of the intracellular signaling pathways that control the initiation of translation. Key words: Muscle, pigs, neonate, protein synthesis, insulin, amino acids


1997 ◽  
Vol 272 (6) ◽  
pp. C1862-C1870 ◽  
Author(s):  
C. N. Inoue ◽  
J. S. Woo ◽  
E. M. Schwiebert ◽  
T. Morita ◽  
K. Hanaoka ◽  
...  

Purinergic receptors play an important role in regulating Cl- secretion in epithelial cells. To explore further the role of these receptors in the intestine, we utilized the human intestinal epithelial cell line, Caco-2, grown on permeable membrane supports and assayed for Cl- secretion by measuring the short-circuit current (Isc). Stimulation of Isc by extracellular nucleotides could be detected by day 4 and increased by day 10 postseeding. The magnitude of stimulation of Isc at 10 microM in cells at day 10 was UTP > ATP > UDP > > 2-methylthioadenosine 5'-triphosphate (2-MeS-ATP) = ADP on the apical side and UTP = 2-MeS-ATP = ATP > ADP > > UDP on the basolateral side. Cross-desensitization studies suggested that two different receptors are expressed in the apical membrane, a P2U purinoceptor and a uridine nucleotide receptor. Two different receptors are also expressed in the basolateral membrane, a P2U receptor and another that reacts with both 2-MeS-ATP and ADP. This latter receptor has an unusual pharmacological profile, with a reactivity for 2-MeS-ATP > ADP but not for ATP. Responses to purinergic receptor agonists were inhibited by pretreatment with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester, thapsigargin, or quinine. Thus we suggest that an increase in intracellular Ca2+ and subsequent opening of Ca(2+)-activated K+ channel play a role in increasing driving force for Cl- to exit across the apical membrane. The role of the cystic fibrosis transmembrane conductance regulator as a Cl- exit pathway on the apical membrane was also established.


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