Premium
Modulation of the Facilitatory Effect of Dopamine at the Neuromuscular Junction by Adenosinergic and Purinergic Receptors
Author(s) -
AlQot Hadir E.,
Elnozahi Neveen A.,
Mohy ElDin Mahmoud M.,
Bistawroos Azza E.,
Abou ZeitHar Mohammed S.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.710.16
Subject(s) - adenosinergic , dopamine , neuromuscular transmission , neuromuscular junction , adenosine , purinergic receptor , adenosine receptor , purinergic signalling , adenosine a1 receptor , adenosine receptor antagonist , chemistry , dopamine receptor , neurotransmission , neuroscience , medicine , endocrinology , biology , receptor , biochemistry , agonist
The objective of this study is to investigate the potential interactions between dopamine and the endogenous neuromodulators; adenosine triphosphate (ATP) and adenosine, at the neuromuscular junction. We have shown previously that dopamine, via the activation of dopamine D 1‐ like receptors, can enhance neuromuscular transmission. ATP and adenosine play a pivotal role in modulation of dopamine function in the central nervous system via purinergic and adenosinergic receptors, respectively. As such, we probed the potential existence of similar interactions in the periphery. We employed in‐vitro experiments using the isolated rat phrenic hemi‐diaphragm preparation which was stimulated indirectly through the stimulation of the phrenic nerve at low frequencies. The parameter used to assess neuromuscular transmission was the percentage change in the amplitude of nerve‐evoked muscle twitches relative to control. In presence of the selective adenosine A 2A receptor antagonist (8‐(3‐Chlorostyryl) caffeine; CSC), the dopamine‐mediated facilitation of indirect muscle twitches was significantly reduced. This implies a positive interaction between dopamine and adenosine, via adenosine A 2A receptors at the motor end‐plate. The enhancement of neuromuscular transmission by dopamine was, unexpectedly, depressed by 1,3‐Dipropyl‐8‐cyclopentylxanthine (DPCPX), a selective adenosine A 1 receptor antagonist. Unlike what would be expected from an inhibitory receptor, the adenosine A 1 receptor appears to contribute a positive effect towards the facilitation mediated by dopamine at the neuromuscular junction. On the other hand, a negative collaboration was established between dopamine and ATP as evidenced by the enhanced dopamine induced‐potentiation of indirect muscle twitches subsequent to the addition of suramin (purinergic antagonist). Hence suggesting that endogenous ATP, via purinergic P 2 receptors, exerts an antagonistic influence on the dopamine effects. In conclusion, these results provide new insights into how dopamine effects can be modulated by co‐transmitters at the neuromuscular junction. Clinically this study highlights potential therapeutic targets for the treatment of disorders characterized by neuromuscular deficits based on the conceived interactions at the motor end‐plate.