Negative cross-talk between presynaptic adenosine and acetylcholine receptors

• Published in: The European journal of neuroscience Vol. 24; no. 1; pp. 105 - 115
• Main Authors: Shakirzyanova, A. V., Bukharaeva, E. A., Nikolsky, E. E., Giniatullin, R. A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.2006
• Subjects: ACh; adenosine; Adenosine - pharmacology; Adenosine A1 Receptor Agonists; Adenosine A1 Receptor Antagonists; Animals; Anura; Autoreceptors - physiology; Calcium - metabolism; Carbachol - pharmacology; In Vitro Techniques; Membrane Potentials; Motor Endplate - drug effects; Motor Endplate - physiology; neuromuscular junction; Neuromuscular Junction - drug effects; Neuromuscular Junction - physiology; Receptor Cross-Talk; Receptor, Adenosine A1 - physiology; Receptor, Muscarinic M2 - agonists; Receptor, Muscarinic M2 - antagonists & inhibitors; Receptor, Muscarinic M2 - physiology; Synapses - physiology
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/j.1460-9568.2006.04884.x

Functional interactions between presynaptic adenosine and acetylcholine (ACh) autoreceptors were studied at the frog neuromuscular junction by recording miniature end‐plate potentials (MEPPs) during bath or local application of agonists. The frequency of MEPPs was reduced by adenosine acting on presynaptic adenosine A1 receptors (EC50 = 1.1 µm) or by carbachol acting on muscarinic M2 receptors (EC50 = 1.8 µm). However, carbachol did not produce the depressant effect when it was applied after the action of adenosine had reached its maximum. This phenomenon implied that the negative cross‐talk (occlusion) had occurred between A1 and M2 receptors. Moreover, the occlusion was receptor‐specific as ATP applied in the presence of adenosine continued to depress MEPP frequency. Muscarinic antagonists [atropine or 1‐[[2‐[(diethylamino)methyl)‐1‐piperidinyl]acetyl]‐5,11‐dihydro‐6H‐pyrido [2,3‐b][1,4]benzodiazepine‐6‐one) (AFDX‐116)] had no effect on the inhibitory action of adenosine and adenosine antagonists [8‐(p‐sulfophenyl)theophylline (8‐SPT) or 1,3‐dipropyl‐8‐cyclopentylxanthine (DPCPX)] had no effect on the action of carbachol. These data suggested that membrane–delimited interactions did not occur between A1 and M2 receptors. Both carbachol and adenosine similarly inhibited quantal release triggered by high potassium, ionomycin or sucrose. These results indicated a convergence of intracellular pathways activated by M2 and A1 receptors to a common presynaptic effector located downstream of Ca2+ influx. We propose that the negative cross‐talk between two major autoreceptors could take place during intense synaptic activity and thereby attenuate the presynaptic inhibitory effects of ACh and adenosine.