Cross talk between facilitatory adenosine A2A, Tachykinin NK1 and
Muscarinic M3 receptors in the rat Mynteric plexus:
on the role of Capsaicin-sensitive Tachykinergic neurons
-
1
Instituto de Ciencias Biomedicas Abel Salazar - Universidade do Porto (ICBAS-UP), Laboratorio de Farmacologia e Neurobiologia, Unidade Multidisciplinar de Investigacao Biomedica (UMIB), Portugal
Gastrointestinal motility relies on the release of acetylcholine (ACh), purines and tachykinins (e.g. substance P) from excitatory enteric neurons. Tachykinins (TK) acting via NK1 and NK3 receptors facilitate cholinergic neurotransmission in the enteric nervous system. Recently, we showed that muscarinic M3 receptors facilitate ACh release indirectly by increasing adenosine outflow from stimulated myenteric neurons leading to the activation of excitatory A2A receptors (Vieira et al., 2009, Neurogastroenterol. Motil. in press). These findings prompted us to investigate the cross talk between facilitatory A2A, M3 and NK1 receptors in the rat myenteric plexus, focusing our attention on the role of tachykinergic nerve fibres which can be selectively eliminated (>95%) by neonatal capsaicin administration (CAP, 50 mg/Kg, SC).
The muscarinic agonist, oxotremorine (Oxo, 300 μM) and the selective adenosine A2A agonist, CGS21680C (CGS, 3 nM), increased evoked (5 Hz, 200 pulses) [3H]-ACh release from myenteric neurons respectively by 34±4% (n=5) and 53±10% (n=5) in controls (C) but were devoid of effects in CAP animals. Selective activation of NK1 receptors with Sar9,Met(O2)11-Substance P (s,m-SP, 300 nM) restored CGS facilitation (46±17%, n=6) to control levels in CAP rats. Cross talk between A2A and NK1 receptors was evaluated using selective antagonists of NK1 (L732128, 20 nM) and A2A (ZM241385, 50 nM) receptors. Pretreatment with s,m-SP did not restore Oxo facilitation (3±7%, n=4) in CAP animals. Incubation of C with the M3 antagonist (J104129, 6 nM) attenuated CGS (3±5%, n=5)-induced facilitation of [3H]-ACh release, but (like in CAP rats) its effect was partially recovered (23±2%, n=3) in the presence of s,m-SP.
Data suggest that facilitation of [3H]-ACh release by A2A receptors requires tonic activation of NK1 receptors by endogenously released TK from CAP-sensitive myenteric neurons. Confocal microscopy studies show that A2A receptors co-localize with cholinergic nerve fibres (labelled with VAChT), but not with CAP-sensitive neurons exhibiting substance P immunoreactivity. Data also indicate that endogenous release of TK (as well as adenosine, see Vieira et al., 2009) may be tightly controlled by M3 receptors. In support of this hypothesis, we showed that CAP-sensitive tachykinergic neurons might be an important source of purines in the rat myenteric plexus (see, Marques et al., 2009, this meeting).
Work supported by FCT (FEDER funding, PTDC/CVT/74462/2006)
Conference:
11th Meeting of the Portuguese Society for Neuroscience, Braga, Portugal, 4 Jun - 6 Jun, 2009.
Presentation Type:
Poster Presentation
Topic:
Neuronal Communication
Citation:
Silva
I,
Vieira
C,
Ferreirinha
F,
Duarte-Araujo
M and
Correia- De-Sa
P
(2009). Cross talk between facilitatory adenosine A2A, Tachykinin NK1 and
Muscarinic M3 receptors in the rat Mynteric plexus:
on the role of Capsaicin-sensitive Tachykinergic neurons.
Front. Neurosci.
Conference Abstract:
11th Meeting of the Portuguese Society for Neuroscience.
doi: 10.3389/conf.neuro.01.2009.11.149
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Received:
12 Aug 2009;
Published Online:
12 Aug 2009.
*
Correspondence:
I. Silva, Instituto de Ciencias Biomedicas Abel Salazar - Universidade do Porto (ICBAS-UP), Laboratorio de Farmacologia e Neurobiologia, Unidade Multidisciplinar de Investigacao Biomedica (UMIB), Porto, Portugal, isabelsds@gmail.com