Intracellular pathways for contraction in gastroesophageal smooth muscle cells.
Intracellular pathways utilized for contraction in response to acetylcholine (ACh), inositol 1,4,5-trisphosphate (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 Ca(2+)-free medium, but contraction of esophageal cells was abolished. KCl-induced contraction of all three cell types was also abolished after incubation in Ca(2+)-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Hillemeier
C
C
C. S. Mott Children's Hospital, University of Michigan, Ann Arbor 48109.
Bitar
K N
KN
Marshall
J M
JM
Biancani
P
P
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002415:Cats; D004947:Esophagus / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005748:Gastric Fundus; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors
D001562:Benzimidazoles; D002147:Calmodulin; D013449:Sulfonamides; C052087:CGS 9343B; D012965:Sodium Chloride; C017967:W 7; D011189:Potassium Chloride; D015544:Inositol 1,4,5-Trisphosphate; D000109:Acetylcholine