Pharmacological Evidence That at Least Two Different Non-adrenergic Non-cholinergic Inhibitory Systems Are Present in the Rat Small Intestine

The nature of the non-adrenergic non-cholinergic (NANC) relaxation was studied in the proximal (duodenum) and distal (ileum) regions of the rat small intestine. In rat duodenum ATP (1 microM-1 mM) produced a concentration-dependent transient relaxation. In ileal segments it produced a slight inhibitory effect at low concentrations (1-10 microM) and a powerful concentration-dependent contractile effect at concentrations equal to or higher than 100 microM. Relaxation similar to that elicited by ATP can be induced in rat duodenum with the nicotinic stimulant dimethylphenylpiperazinium (DMPP, 0.1 mM) and with gamma-aminobutyric acid (GABA, 1 mM). DMPP had a similar inhibitory effect on distal ileum while GABA barely affected spontaneous activity in this preparation. TTX (0.5 microM)-sensitive relaxation can be elicited in both duodenal and ileal tissues by field stimulation at 0.1 Hz. In the rat duodenum this nerve-mediated relaxation was sensitive to ATP desensitization, nucleotide pyrophosphatase (0.25 U/ml) but resistant to the proteolytic enzyme alpha-chymotrypsin (2 U/ml). On the other hand the field stimulation (0.1 Hz)-induced relaxation in the distal ileum was unaffected by ATP desensitization (by using both low or high concentration of ATP) and by incubation of the preparation with the two enzymes. These findings provide pharmacological evidence that low frequency field stimulation activates at least two different inhibitory NANC systems in the rat small intestine. Adenosine-5'-triphosphate (ATP) appears to be involved as a major transmitter in the duodenal but not in the ileal NANC inhibitory mechanism(s).