Guanine-based purines affects the enteric cholinergic neurotransmission via amechanism not involving membrane receptors

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Increasing evidence indicate that guanine-basedpurines, known as modulators of intracellularprocesses, can exert extracellular effects, raisingthe possibility of the existence of specific receptorsfor these compounds. We investigated if guaninebasedpurine receptors may be present in the rodentgastrointestinal tract modulating intestinalcontractility, as the well known adenine-basedpurine receptors. Experiments were performed invitro recording spontaneous and neurally-evokedcontractile activity, as changes in isometric tension,in mouse distal colon circular muscle.Guanosine up to 3 mM or guanine up to 1 mM, didnot affect the spontaneous mechanical activity, butthey significantly and reversibly reduced theamplitude of the nerve evoked cholinergiccontractions. Both compounds did not affect thedirect contractile responses to muscarinic agonist.No desensitization of the response was observed.Guanine-based purine effects were not modified byadenine-based purine receptor antagonists or byadenylyl or guanilyl cyclase inhibitors.Dipyridamole or NBTI, nucleoside uptakeinhibitors markedly reduced the guanosine effectswhilst guanine effects were prevented in thepresence of adenine, competitive inhibitor ofnucleobase uptake.Our data indicate that guanosine and guanine areable to modulate negatively the excitatorycholinergic neurotransmission in the mouse coloncircular muscle. Guanine-based purines appear toact on prejunctional release of acetylcholine. Theireffects are dependent by their cellular uptake, andindependent by adenine based purine receptors.
Original languageEnglish
Number of pages1
Publication statusPublished - 2011


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