Development of motor response to intramural nerve stimulation and to drugs in rat small intestine.

1. The onset and development of functional innervation and transmitter reactivity in the small intestine, isolated from foetal and neonatal rat, was examined in relation to the development of two muscle layers. 2. About half of the preparations tested at embryonic day 15 responded to electrical field stimulation, although both acetylcholine (ACh, 1 micro M) and excess K (50 mM) evoked a response in all preparations. The response to these stimuli was the extension of the preparation longitudinally. All six preparations examined at embryonic day 16 extended in response to electrical field stimulation. 3. The extension response to electrical field stimulation was observed up to embryonic day 19. Then, the response changed to a biphasic one and finally to shortening after 4-days postnatal. The responses to electrical field stimulation were blocked by tetrodotoxin (TTX, 0.3 micro M) or atropine (0.3 micro M). The response to ACh and excess K similarly changed and became only a shortening at embryonic day 21 and 6-days postnatal, respectively. 4. The extension and biphasic responses produced by these stimuli were invariably converted to shortening after the preparation had been opened longitudinally. 5. The pD2 value for ACh was 6.74-7.37 during the period embryonic day 15-6-days postnatal. 6. Theses results suggest that in the rat intestine, functional cholinergic innervation is established at least by embryonic day 16. In the early stages, the development of the circular muscle layer precedes the preparation in response to stimuli. The reverse takes place following the development of the longitudinal muscle layer.