Pharmacological evidence for the involvement of the cAMP cascade in sensory fatigue in Drosophila

1990 ◽  
Vol 167 (3) ◽  
Author(s):  
Gabriel Corfas ◽  
Yadin Dudai
Keyword(s):  
Sensory Fatigue ◽  
Camp Cascade

Protein Kinase A Mediates the Modulation of the Slow Ca2+-Dependent K+ Current,I sAHP, by the Neuropeptides CRF, VIP, and CGRP in Hippocampal Pyramidal Neurons

2000 ◽  
Vol 83 (4) ◽  
pp. 2071-2079 ◽  
Author(s):  
Trude Haug ◽  
Johan F. Storm
Keyword(s):  
Protein Kinase ◽  
Time Course ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Cell Voltage ◽  
Dependent Protein Kinase ◽  
Hippocampal Pyramidal Neurons ◽  
Camp Dependent Protein Kinase ◽  
Dependent Protein ◽  
Camp Cascade

We have studied modulation of the slow Ca2+-activated K+current ( I sAHP) in CA1 hippocampal pyramidal neurons by three peptide transmitters: corticotropin releasing factor (CRF, also called corticotropin releasing hormone, CRH), vasoactive intestinal peptide (VIP), and calcitonin gene–related peptide (CGRP). These peptides are known to be expressed in interneurons. Using whole cell voltage clamp in hippocampal slices from young rats, in the presence of tetrodotoxin (TTX, 0.5 μM) and tetraethylammonium (TEA, 5 mM), I sAHP was measured after a brief depolarizing voltage step eliciting inward Ca2+ current. Each of the peptides CRF (100–250 nM), VIP (400 nM), and CGRP (1 μM) significantly reduced the amplitude of I sAHP. Thus the I sAHP amplitude was reduced to 22% by 100 nM CRF, to 17% by 250 nM CRF, to 22% by 400 nM VIP, and to 40% by 1 μM CGRP. We found no consistent concomitant changes in the Ca2+ current or in the time course of I sAHP for any of the three peptides, suggesting that the suppression of I sAHP was not secondary to a general suppression of Ca2+ channel activity. Because each of these peptides is known to activate the cyclic AMP (cAMP) cascade in various cell types, and I sAHP is known to be suppressed by cAMP via the cAMP-dependent protein kinase (PKA), we tested whether the effects on I sAHP by CRF, VIP, and CGRP are mediated by PKA. Intracellular application of the PKA-inhibitor Rp-cAMPS significantly reduced the suppression of I sAHP by CRF, VIP, and CGRP. Thus with 1 mM Rp-cAMPS in the recording pipette, the average suppression of I sAHP was reduced from 78 to 26% for 100 nM CRF, from 83 to 32% for 250 nM CRF, from 78 to 30% for 400 nM VIP, and from 60 to 7% for 1 μM CGRP. We conclude that CRF, VIP, and CGRP suppress the slow Ca2+-activated K+ current, I sAHP, in CA1 hippocampal pyramidal neurons by activating the cAMP-dependent protein kinase, PKA. Together with the monoamine transmitters norepinephrine, serotonin, histamine, and dopamine, these peptide transmitters all converge on the cAMP cascade modulating I sAHP.

The cAMP cascade and mitochondrial oxidative phosphorylation. Physiopathological implications

2002 ◽  
Vol 30 (1) ◽  
pp. A7-A7
Author(s):  
S. Papa ◽  
A.M. Sardanelli ◽  
S. Scacco ◽  
V. Petruzzella ◽  
Z. Technikova-Dobrova ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Camp Cascade

c-myc expression is controlled by the mitogenic cAMP-cascade in thyrocytes

1996 ◽  
Vol 168 (1) ◽  
pp. 59-70 ◽  
Author(s):  
Isabelle Pirson ◽  
Katia Coulonval ◽  
Françoise Lamy ◽  
Jacques E. Dumont
Keyword(s):  
Camp Cascade

Stimulators of the cAMP Cascade Reverse Amnesia Induced by Intra-amygdala but Not Intrahippocampal KN-62 Administration

1999 ◽  
Vol 71 (1) ◽  
pp. 94-103 ◽  
Author(s):  
Daniela M. Barros ◽  
Luciana A. Izquierdo ◽  
Marcia K. Sant'Anna ◽  
João Quevedo ◽  
Jorge H. Medina ◽  
...  
Keyword(s):  
Camp Cascade

Involvement of cAMP-Dependent Protein Kinase in μ-Opioid Modulation of NMDA-Mediated Synaptic Currents

1997 ◽  
Vol 78 (2) ◽  
pp. 759-766 ◽  
Author(s):  
Cui-Wei Xie ◽  
Darrell V. Lewis
Keyword(s):  
Nmda Receptor ◽  
Protein Kinase ◽  
G Proteins ◽  
Inhibitory Action ◽  
Granule Cells ◽  
Inhibitory Effect ◽  
Dependent Protein Kinase ◽  
Camp Dependent Protein Kinase ◽  
Dependent Protein ◽  
Camp Cascade

Xie, Cui-Wei and Darrell V. Lewis. Involvement of cAMP-dependent protein kinase in μ-opioid modulation of NMDA-mediated synaptic currents. J. Neurophysiol. 78: 759–766, 1997. We have previously reported dual effects of μ-opioids on N-methyl-d-aspartate (NMDA)-receptor-mediated synaptic events in the hippocampal dentate gyrus: an indirect facilitating effect via suppression of GABAergic interneurons (disinhibition) and a direct inhibitory effect in the presence of γ-aminobutyric acid-A (GABAA) antagonists. The cellular mechanism underlying the inhibitory effect of μ-opioids remains to be determined. In the present study we examine the role of adenosine 3′,5′-cyclic monophosphate (cAMP)-dependent protein kinase (PKA) in μ-opioid-induced inhibition of NMDA currents in rat hippocampal slices. NMDA-receptor-mediated excitatory postsynaptic currents (NMDA EPSCs) were evoked by stimulating the lateral perforant path and were recorded from dentate granule cells with the use of whole cell voltage-clamp techniques in the presence of the GABAA antagonist and a non-NMDA type of glutamate receptor antagonist. Two selective μ-agonists, [N-MePhe3, D-Pro4]-morphiceptin and [D-Ala2, N-MePhe4, Gly-ol5]-enkephalin, induced dose-dependent inhibition of NMDA EPSCs in a concentration range of 0.3–10 μM. This inhibitory effect could be completely reversed by the opioid antagonists naloxone or prevented by a selective μ-antagonist cyprodime, but was not affected by removal of Mg2+ from the external perfusion medium. Intracellular application of pertussis toxin (PTX) into the granule cell via whole cell recording pipettes completely prevented μ-opioid-induced reduction in NMDA currents, suggesting that a postsynaptic mechanism involving PTX-sensitive G proteins might be responsible for the inhibitory action of μ-opioids. Further studies were conducted to identify the intracellular messengers that coupled with G proteins and transduced the effect of μ-opioids in granule cells. The adenylate cyclase activator forskolin was found to enhance NMDA-receptor-mediated synaptic responses and to reverse the inhibitory effect of μ-opioids. Sp-cAMPS, a specific PKA activator, also enhanced NMDA EPSCs, whereas the PKA inhibitor Rp-cAMPS reduced NMDA EPSCs and occluded further inhibition of the current by μ-opioids. These findings strongly suggest that NMDA receptor function is subject to the modulation by PKA, and that μ-opioids can inhibit NMDA currents through suppression of the cAMP cascade in the postsynaptic neuron. Combined with our previous findings, the present results also indicate that μ-opioids can modulate NMDA-receptor-mediated synaptic activity in a complex manner. The net effect of μ-opioids in the dentate gyrus may depend on the interplay between its disinhibitory action, which facilitates NMDA-receptor-mediated responses, and its inhibitory action on the cAMP cascade.

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