Intracellular pathways utilized for contraction in response to acetylcholine (ACh), inositol 1,4,5-triphosphate (IP3), and KCl were examined in isolated circular smooth cells from the esophagus, lower esophageal sphincter (LES), and fundus. In physiological nutrient salt solution (PSS) intact muscle cells isolated from these three tissues responded in a similar dose-dependent manner to ACh. In all tissues the contractile response to ACh was maximal at 30 s. Contraction of smooth muscle cells from LES and fundus did not change after incubation in Ca2+-free medium, but contraction of esophageal cells was abolished. KCl-induced contraction of all three cell types was also abolished after incubation in Ca2+-free medium. After permeabilization with saponin in cytosolic (low Ca2+) salt solution, muscle cells from LES and fundus contracted in a dose-dependent manner in response to IP3, whereas cells from esophagus did not contract. Contraction of permeabilized LES and fundic cells in response to ACh was the same as that of intact muscle cells. Response to IP3 was more rapid than response to ACh; it reached 85% of maximum by 5 s and peaked at 15 s. Calmodulin antagonists W-7 and CGS 9343B blocked contraction in response to ACh in intact cells from LES and fundus but had no effect on ACh-induced contraction in esophageal cells. These antagonists blocked IP3-induced contraction in permeabilized cells from LES and fundus. KCl-induced contraction in intact cells from all three tissues was not blocked by either W-7 or CGS 9343B. These data suggest that calmodulin antagonists block contraction mediated by release of intracellular Ca2+ induced by ACh or IP3. These antagonists have no effect on contraction mediated by influx of extracellular Ca2+, as occurs in esophagus with ACh and with KCl in all three tissues. The data are consistent with the hypothesis that different intracellular pathways may be utilized for contraction, depending on the sources of activator Ca2+.
|Original language||English (US)|
|Journal||American Journal of Physiology - Gastrointestinal and Liver Physiology|
|Issue number||5 23-5|
|State||Published - 1991|
All Science Journal Classification (ASJC) codes
- Physiology (medical)