Dual Excitatory and Inhibitory Effect of Nitric Oxide on Peristalsis in the Guinea Pig Intestine

• Published in: The Journal of pharmacology and experimental therapeutics 1997-01, Vol.280 (1), p.154-161
• Main Authors: Holzer, P, Lippe, I T, Tabrizi, A L, Lènárd, L, Barthó, L
• Format: Article
• Language: English
• Subjects: Animals; Apamin - pharmacology; Female; Guinea Pigs; Ileum - drug effects; Ileum - physiology; Male; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide - physiology; Nitroprusside - pharmacology; Peristalsis
• ISSN: 0022-3565; 1521-0103

The implications of the enteric neurotransmitter nitric oxide (NO) in intestinal peristalsis were investigated. Propulsive motility in isolated segments of the guinea pig ileum was triggered by intraluminal fluid infusion to distend the intestinal wall, and the pressure threshold for eliciting peristaltic waves was used to quantify facilitation (decrease in threshold) or inhibition (increase in threshold) of peristalsis. The NO donor sodium nitroprusside (0.1–100 μM serosally) caused a prompt facilitation of peristalsis, which in the presence of a threshold concentration of atropine (10 nM) was followed by a concentration-related blockade of peristalsis. Further analysis showed that sodium nitroprusside (10 and 100 μM) first relaxed, then contracted, and finally relaxed the longitudinal muscle of the guinea pig isolated ileum, the contraction being blocked by atropine (1 μM). Inhibition of NO synthase by N G -nitro- L -arginine methylester (100–300 μM) facilitated peristalsis, an effect that was reduced by L -arginine (1 mM) but left unaltered by atropine (10 nM). Blockade of inhibitory neuromuscular transmission by successive exposure of the ileum to apamin (0.5 μM) and N G -nitro- L -arginine methylester (300 μM), in this or reverse order, disrupted the coordinated pattern of peristalsis and caused irregular nonpropulsive contractions of the circular muscle. It is concluded that NO has a dual excitatory and inhibitory effect on intestinal motility. The excitatory effect involves cholinergic motor neurons, whereas the inhibitory effect reflects relaxation of intestinal muscle. Abolition of peristalsis by combined exposure to N G -nitro- L -arginine methylester and apamin attests to an essential role of enteric inhibitory motor neurons in the coordination of propulsive motility in the intestine.