title: Negative cross-talk between presynaptic adenosine and acetylcholine receptors.
abstract: 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 (EC(50) = 1.1 microm) or by carbachol acting on muscarinic M2 receptors (EC(50) = 1.8 microm). 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 Ca(2+) 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.
authors.affiliation: Kazan Institute of Biochemistry and Biophysics KSC RAS, 420111 Kazan, Tatarstan, Russia.
authors.forename: A V
authors.initials: AV
authors.lastname: Shakirzyanova
authors.forename: E A
authors.initials: EA
authors.lastname: Bukharaeva
authors.forename: E E
authors.initials: EE
authors.lastname: Nikolsky
authors.forename: R A
authors.initials: RA
authors.lastname: Giniatullin
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D001001:Anura; D017660:Autoreceptors / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials; D009045:Motor Endplate / Q000187:drug effects / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D020239:Receptor Cross-Talk; D043682:Receptor, Adenosine A1 / Q000502:physiology*; D043585:Receptor, Muscarinic M2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013569:Synapses / Q000502:physiology
chemical_list: D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D017660:Autoreceptors; D043682:Receptor, Adenosine A1; D043585:Receptor, Muscarinic M2; D002217:Carbachol; D000241:Adenosine; D002118:Calcium