Int J Oral Biol.  2011 Jun;36(2):83-89.

Involvement of Crosstalk Between cAMP and cGMP in Synaptic Plasticity in the Substantia Gelatinosa Neurons

Affiliations
  • 1Department of Neurobiology and Physiology, School of Dentistry, Seoul National University, Seoul 110-749, Korea. odolbae@snu.ac.kr
  • 2Department of Physiology, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
  • 3Department of Physiology, School of Medicine, Hanyang University, Seoul 133-791, Korea.

Abstract

Substantia gelatinosa (SG) neurons receive synaptic inputs from primary afferent Adelta- and C-fibers, where nociceptive information is integrated and modulated by numerous neurotransmitters or neuromodulators. A number of studies were dedicated to the molecular mechanism underlying the modulation of excitability or synaptic plasticity in SG neurons and revealed that second messengers, such as cAMP and cGMP, play an important role. Recently, cAMP and cGMP were shown to downregulate each other in heart muscle cells. However, involvement of the crosstalk between cAMP and cGMP in neurons is yet to be addressed. Therefore, we investigated whether interaction between cAMP and cGMP modulates synaptic plasticity in SG neurons using slice patch clamp recording from rats. Synaptic activity was measured by excitatory post-synaptic currents (EPSCs) elicited by stimulation onto dorsal root entry zone. Application of 1 mM of 8-bromoadenosine 3,5-cyclic monophosphate (8-Br-cAMP) or 8-bromoguanosine 3,5-cyclic monophosphate (8-Br-cGMP) for 15 minutes increased EPSCs, which were maintained for 30 minutes. However, simultaneous application of 8-Br-cAMP and 8-Br-cGMP failed to increase EPSCs, which suggested antagonistic cross-talk between two second messengers. Application of 3-isobutyl-1-methylxanthine (IBMX) that prevents degradation of cAMP and cGMP by blocking phosphodiesterase (PDE) increased EPSCs. Co-application of cAMP/cGMP along with IBMX induced additional increase in EPSCs. These results suggest that second messengers, cAMP and cGMP, might contribute to development of chronic pain through the mutual regulation of the signal transduction.

Keyword

substantia gelatinosa; spinal cord slice; patch clamp; cAMP; cGMP

MeSH Terms

1-Methyl-3-isobutylxanthine
Adenosine
Animals
Chronic Pain
Guanosine
Myocytes, Cardiac
Neurons
Neurotransmitter Agents
Plastics
Rats
Second Messenger Systems
Signal Transduction
Spinal Nerve Roots
Substantia Gelatinosa
1-Methyl-3-isobutylxanthine
Adenosine
Guanosine
Neurotransmitter Agents
Plastics
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