title: Modulation of dopamine-mediated facilitation at the neuromuscular junction of Wistar rats: A role for adenosine A1/A2A receptors and P2 purinoceptors.
abstract: This study aims to understand how dopamine and the neuromodulators, adenosine and adenosine triphosphate (ATP) modulate neuromuscular transmission. Adenosine and ATP are well-recognized for their regulatory effects on dopamine in the central nervous system. However, if similar interactions occur at the neuromuscular junction is unknown. We hypothesize that the activation of adenosine A1/A2A and/or P2 purinoceptors may influence the action of dopamine on neuromuscular transmission. Using the rat phrenic nerve hemi-diaphragm, we assessed the influence of dopamine, adenosine and ATP on the height of nerve-evoked muscle twitches. We investigated how the selective blockade of adenosine A1 receptors (2.5nM DPCPX), adenosine A2A receptors (50nM CSC) and P2 purinoceptors (100μM suramin) modified the effects of dopamine. Dopamine alone increased indirect muscle contractions while adenosine and ATP either enhanced or depressed nerve-evoked muscle twitches in a concentration-dependent manner. The facilitatory effects of 256μM dopamine were significantly reduced to 29.62±2.79% or 53.69±5.45% in the presence of DPCPX or CSC, respectively, relative to 70.03±1.57% with dopamine alone. Alternatively, the action of 256μM dopamine was potentiated from 70.03±1.57, in the absence of suramin, to 86.83±4.36%, in the presence of suramin. It can be concluded that the activation of adenosine A1 and A2A receptors and P2 purinoceptors potentially play a central role in the regulation of dopamine effects at the neuromuscular junction. Clinically this study offers new insights for the indirect manipulation of neuromuscular transmission for the treatment of disorders characterized by motor dysfunction.
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Alexandria University, Azarita, P.O. Box: 21521, Alexandria, Egypt.
authors.forename: Neveen A
authors.initials: NA
authors.lastname: Elnozahi
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Alexandria University, Azarita, P.O. Box: 21521, Alexandria, Egypt. Electronic address: halqot@uwo.ca.
authors.forename: Hadir E
authors.initials: HE
authors.lastname: AlQot
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Alexandria University, Azarita, P.O. Box: 21521, Alexandria, Egypt.
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: Mohy El-Din
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Alexandria University, Azarita, P.O. Box: 21521, Alexandria, Egypt.
authors.forename: Azza E
authors.initials: AE
authors.lastname: Bistawroos
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Alexandria University, Azarita, P.O. Box: 21521, Alexandria, Egypt.
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Abou Zeit-Har
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000502:physiology*; D058916:Adenosine A1 Receptor Antagonists / Q000008:administration & dosage; D058917:Adenosine A2 Receptor Antagonists / Q000008:administration & dosage; D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000502:physiology*; D000818:Animals; D004298:Dopamine / Q000008:administration & dosage / Q000502:physiology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D009469:Neuromuscular Junction / Q000502:physiology*; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology; D058919:Purinergic P2 Receptor Antagonists / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000502:physiology*; D043705:Receptor, Adenosine A2A / Q000502:physiology*; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D009435:Synaptic Transmission
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D058919:Purinergic P2 Receptor Antagonists; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate; D000241:Adenosine; D004298:Dopamine
keywords: acetylcholine; adenosine; adenosine triphosphate; dopamine; neuromodulators; neuromuscular junction