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Nitrergic–purinergic interactions in rat distal colon motility
Author(s) -
Crombruggen K. Van,
Lefebvre R. A.
Publication year - 2004
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1046/j.1365-2982.2003.00454.x
Subject(s) - purinergic receptor , apamin , soluble guanylyl cyclase , chemistry , tetrodotoxin , stimulation , nitric oxide , nitric oxide synthase , inhibitory postsynaptic potential , medicine , endocrinology , potassium channel , adenosine , receptor , biochemistry , biology , guanylate cyclase
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 Ca 2+ ‐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‐ γ ‐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.