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  • Title: Nitrergic-purinergic interactions in rat distal colon motility.
    Author: Van Crombruggen K, Lefebvre RA.
    Journal: Neurogastroenterol Motil; 2004 Feb; 16(1):81-98. PubMed ID: 14764208.
    Abstract:
    Responses of rat distal colon circular muscle strips to exogenous nitric oxide (NO) and adenosine 5'-triphosphate (ATP) and to electrical field stimulation (EFS) were assessed in the absence/presence of various agents that interfere with nitrergic-purinergic pathways. Exogenous NO (10-6 to 10-4 mol L-1) elicited concentration-dependent, tetrodotoxin (TTX)-insensitive relaxations. The soluble guanylyl-cyclase (sGC) inhibitor 1H[1,2,4,]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) reduced duration and amplitude; the small conductance Ca2+-sensitive K+ (SK)-channel blocker apamin (APA) only shortened the relaxations. ODQ + APA showed a marked inhibitory effect on duration and amplitude. TTX, APA, the NO-synthase inhibitor N(omega)-nitro-l-arginine methyl ester (l-NAME) and the purinergic receptor P2Y antagonist Reactive Blue 2 (RB2) shortened the relaxations by exogenous ATP (10-3 mol L-1) but did not influence the amplitude. ODQ had no effect. TTX + l-NAME did not yield a more pronounced inhibitory effect than TTX alone. The effect of ATP-gamma-S was similar to that of ATP. Electrical field stimulation (EFS) (40 V, 0.05 ms, 0.5-4 Hz for 30 s) yielded TTX-sensitive relaxations that were not altered by l-NAME, ODQ or RB2. APA shortened the relaxations. l-NAME + APA nearly abolished these relaxations. ODQ + APA and RB2 +l-NAME reduced the duration. These results suggest that distinct sets of small conductance SK-channels are involved in the amplitude and the duration of the relaxations and that NO increases their sensitivity to NO and ATP via guanosine 3',5'-cyclic monophosphate (cGMP). ATP elicits relaxations via P2Y receptors with subsequent activation of SK-channels and induces neuronal release of NO. Both nitrergic and purinergic pathways must be blocked to inhibit EFS-induced relaxations.
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