Evidence for muscarinic inhibitory neurotransmission in rodent small intestine.

The influence of cholinergic and noncholinergic inhibitory nerves was examined in circular and longitudinal muscle from the duodenum. Rodent proximal small intestine was cut into strips measuring 6.0 x 10.0 mm. Strips cut along the oral-caudal axis were called longitudinal strips, whereas those cut 90 degrees to that axis were called circular strips. The strips were stretched to their optimal lengths and subjected to electrical field stimulation in the presence of various concentrations of atropine, pirenzepine or McN-A-343-11. All three drugs inhibited field-stimulated contraction responses and produced or augmented relaxation responses in both muscle layers. All relaxation responses were abolished by tetrodotoxin, indicating they were due to excitation of inhibitory nerves. For each response examined atropine was significantly more potent than pirenzepine (relative potency ratio, 13.36-95.74). The inhibitory effect of McN-A-343-11 on longitudinal muscle was antagonized by both atropine and pirenzepine, indicating the recruitment of cholinergic inhibitory nerves. Neither atropine nor pirenzepine had any effects on inhibitory responses produced by McN-A-343-11 in circular muscle, indicating the recruitment of noncholinergic inhibitory nerves. McN-A-343-11 also increased spontaneous contraction amplitudes in both muscle layers by a direct (tetrodotoxin-resistant) effect on smooth muscle. This effect was also antagonized by atropine and pirenzepine. Thus, both cholinergic and noncholinergic nerves participate in inhibitory neuromuscular transmission in the small intestine. Circular muscle is dominated by a noncholinergic inhibitory innervation. Longitudinal muscle appears to be controlled by both cholinergic and noncholinergic inhibitory nerves.