scholarly journals Enhanced Adenosine A2A Receptor Facilitation of Synaptic Transmission in the Hippocampus of Aged Rats

2003 ◽  
Vol 90 (2) ◽  
pp. 1295-1303 ◽  
Author(s):  
Nelson Rebola ◽  
Ana M. Sebastião ◽  
Alexandre de Mendonça ◽  
Catarina R. Oliveira ◽  
J. A. Ribeiro ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Synaptic Transmission ◽  
Receptor Agonist ◽  
Nerve Terminals ◽  
Aged Rats ◽  
Receptor Density ◽  
Young Rats ◽  
Kinase C ◽  
Fepsp Slope ◽  
Kinase A

Adenosine either inhibits or facilitates synaptic transmission through A1 or A2A receptors, respectively. Since A2A receptor density increases in the limbic cortex of aged (24 mo) compared with young adult rats (2 mo), we tested if A2A receptor modulation of synaptic transmission was also increased in aged rats. The A2A receptor agonist, CGS21680 (10 nM), caused a larger facilitation of the field excitatory postsynaptic potential (fEPSP) slope in hippocampal slices of aged (38%) than in young rats (19%), an effect prevented by the A2A receptor antagonist, ZM241385 (20 nM). In contrast to young rats, where CGS21680 facilitation of fEPSPs is prevented by the protein kinase C inhibitor, chelerythrine (6 μM), but not by the protein kinase A inhibitor, H-89 (1 μM), the CGS21680 -induced facilitation of fEPSP slope in aged rats was prevented by H-89 (1 μM) but not by chelerythrine (6 μM). Also, in contrast to the β–receptor agonist, isoproterenol (30 μM), CGS21680 (100–1,000 nM) enhanced cAMP levels in hippocampal nerve terminals of aged but not young rats. Finally, we observed a significant increase of both the binding density of [3H]CGS 21680 and the [3H]ZM241385 as well as of the anti-A2A receptor immunoreactivity in hippocampal nerve terminal membranes from aged compared with young rats. This shows that A2A receptor-mediated facilitation of hippocampal synaptic transmission is larger in aged than young rats due to increased A2A receptor density in nerve terminals and to the modified transducing system operated by A2A receptors, from a protein kinase C mediated control of A1 receptors into a direct protein kinase A dependent facilitation of synaptic transmission.

Cross Talk Between A1 and A2A Adenosine Receptors in the Hippocampus and Cortex of Young Adult and Old Rats

1999 ◽  
Vol 82 (6) ◽  
pp. 3196-3203 ◽  
Author(s):  
Luísa V. Lopes ◽  
Rodrigo A. Cunha ◽  
J. A. Ribeiro
Keyword(s):  
Protein Kinase C ◽  
Young Adult ◽  
Protein Kinase ◽  
Synaptic Transmission ◽  
Protein Kinase A ◽  
Receptor Activation ◽  
Cgs 21680 ◽  
Kinase C ◽  
Population Spike Amplitude ◽  
Kinase A

Adenosine modulates synaptic transmission by acting on inhibitory A1 and facilitatory A2A receptors, the densities of which are modified in aged animals. We investigated how A2A receptor activation influences A1receptor function and whether this interaction is modified in aged rats. In hippocampal and cortical nerve terminals from young adult (6 wk), but not old rats (24 mo), the A2A receptor agonist, 2-[4-(2-carboxyethyl) phenethylamino]-5′- N-ethylcarboxamidoadenosine (CGS 21680; 30 nM) decreased the binding affinity of a selective A1 receptor agonist, cyclopentyladenosine (CPA), an effect prevented by the A2A antagonist, (4-(2-[7-amino-2-(2-furyl {1,2,4}-triazolo{2,3-a {1,3,5}triazin-5-yl-aminoethyl)phenol (ZM 241385, 20 nM). This effect of CGS 21680 required intact nerve terminals and was also observed in the absence of Ca2+. This A2A-induced “desensitization” of A1receptors was prevented by the protein kinase C inhibitor, chelerythrine (6 μM), and was not detected in the presence of the protein kinase C activator, phorbol-12,13-didecanoate (250 nM), which itself caused a reduction in binding affinity for CPA. The protein kinase A inhibitor, N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (10 μM), and the protein kinase A activator, 8-Br-cAMP (1 mM), had no effects on the A2A-induced A1 receptor desensitization. This A2A-induced A1 receptor desensitization had a functional correlation because CGS 21680 (10 nM) attenuated by 40% the inhibition caused by CPA (10 nM) on CA1 area population spike amplitude in hippocampal slices. This A2A/A1 interaction may explain the attenuation by adenosine deaminase (2 U/ml), which removes tonic A1inhibition, of the facilitatory effect of CGS 21680 on synaptic transmission. The requirement of tonic A1 receptor activation for CGS 21680 to induce facilitation of synaptic transmission was reinforced by the observation that the A1receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (20 nM) prevented CGS 21680 (10 nM) facilitation of population spike amplitude. The present results show the ability of A2A receptors to control A1 receptor function in a manner mediated by protein kinase C, but not protein kinase A, in young adult but not in aged rats.

Phosphorylation of NADPH oxidase activator 1 (NOXA1) on serine 282 by MAP kinases and on serine 172 by protein kinase C and protein kinase A prevents NOX1 hyperactivation

2010 ◽  
Vol 24 (6) ◽  
pp. 2077-2092 ◽  
Author(s):  
Yolande Kroviarski ◽  
Maya Debbabi ◽  
Rafik Bachoual ◽  
Axel Pe´rianin ◽  
Marie‐Anne Gougerot‐Pocidalo ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Nadph Oxidase ◽  
Protein Kinase A ◽  
Map Kinases ◽  
Kinase C ◽  
Kinase A

scholarly journals Pituitary adenylate cyclase activating polypeptide as a novel hypophysiotropic factor in fish

2000 ◽  
Vol 78 (3) ◽  
pp. 329-343 ◽  
Author(s):  
Anderson OL Wong ◽  
Wen Sheng Li ◽  
Eric KY Lee ◽  
Mei Yee Leung ◽  
Lai Yin Tse ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Adenylate Cyclase ◽  
Protein Kinase A ◽  
Anterior Pituitary ◽  
Kinase C ◽  
Pituitary Adenylate Cyclase ◽  
Pacap Receptors ◽  
Kinase A

Pituitary adenylate cyclase activating polypeptide (PACAP) is a novel member of the secretin-glucagon peptide family. In mammals, this peptide has been located in a wide range of tissues and is involved in a variety of biological functions. In lower vertebrates, especially fish, increasing evidence suggests that PACAP may function as a hypophysiotropic factor regulating pituitary hormone secretion. PACAP has been identified in the brain-pituitary axis of representative fish species. The molecular structure of fish PACAP is highly homologous to mammalian PACAP. The prepro-PACAP in fish, however, is distinct from that of mammals as it also contains the sequence of fish GHRH. In teleosts, the anterior pituitary is under direct innervation of the hypothalamus and PACAP nerve fibers have been identified in the pars distalis. Using the goldfish as a fish model, mRNA transcripts of PACAP receptors, namely the PAC1 and VPAC1 receptors, have been identified in the pituitary as well as in various brain areas. Consistent with the pituitary expression of PACAP receptors, PACAP analogs are effective in stimulating growth hormone (GH) and gonadotropin (GTH)-II secretion in the goldfish both in vivo and in vitro. The GH-releasing action of PACAP is mediated via pituitary PAC1 receptors coupled to the adenylate cyclase-cAMP-protein kinase A and phospholipase C-IP3-protein kinase C pathways. Subsequent stimulation of Ca2+ entry through voltage-sensitive Ca2+ channels followed by activation of Ca2+-calmodulin protein kinase II is likely the downstream mechanism mediating PACAP-stimulated GH release in goldfish. Although the PACAP receptor subtype(s) and the associated post-receptor signaling events responsible for PACAP-stimulated GTH-II release have not been characterized in goldfish, these findings support the hypothesis that PACAP is produced in the hypothalamus and delivered to the anterior pituitary to regulate GH and GTH-II release in fish.Key words: PACAP, VIP, PAC1 receptor, VPAC1 receptor, VPAC2 receptor, growth hormone, gonadotropin-II, cAMP, protein kinase A, protein kinase C, calcium, pituitary cells, goldfish, and teleost.

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