Can guanine-based purines be considered modulators of intestinal motility in rodents?

Adenine-based purines play a pivotal role in the control of gastrointestinal motility in rodents Recently guanine-based purines have been also shown to exert extracellular effects in the central nervous system raising the possibility of the existence of distinct receptors for guanine based purines Thus it seems likely to speculate that also guanine-based purines may play a role in the modulation of the intestinal contractility Spontaneous and neurally-evoked mechanical activity was recorded in vitro as changes in isometric tension in circular muscle strips from mouse distal colon Guanosine up to 3 mM or guanine up to 1 mM failed to affect the spontaneous mechanical activity but reduced the amplitude of the electrical field stimulation (EFS) induced cholinergic contractions without affecting the early nitrergic relaxation Both compounds failed to affect the direct contractile responses evoked by carbachol No desensitization of the response was observed Guanine-based purine effects were not altered by theophylline P1 purinoceptor antagonist by PPADS or suramin P2 purinoceptor antagonists by ODQ guanilyl cyclase inhibitor or by DDA adenylyl cyclase inhibitor Nucleoside uptake inhibitors dipyridamole or 6-[(4-Nitrobenzyl)thio]-9 beta-D-ribofuranosylpurine (NBTI) antagonized the inhibitory effects induced by guanosine without interfering with guanine On the contrary adenine a competitive inhibitor of nucleobase uptake antagonized guanine-Induced effects In conclusion our data indicate that guanosine and guanine are able to modulate negatively the excitatory cholinergic neurotransmission in the circular muscle layer of mouse colon Guanine-based purines appear to interfere with prejunctional acethylcoline release Their effects are dependent by their cellular uptake and independent by adenine-based purine receptors (C) 2010 Elsevier B V All rights reserved