Role of calcium and calmodulin in ciliary stimulation induced by acetylcholine.
The goal of this work was to elucidate the molecular events underlying stimulation of ciliary beat frequency (CBF) induced by acetylcholine (ACh) in frog esophagus epithelium. ACh induces a profound increase in CBF and in intracellular Ca(2+) concentration ([Ca(2+)](i)) through M(1) and M(3) muscarinic receptors. The [Ca(2+)](i) slowly decays to the basal level, while CBF stabilizes at an elevated level. These results suggest that ACh triggers Ca(2+)-correlated and -uncorrelated modes of ciliary stimulation. ACh response is abolished by the phospholipase C (PLC) inhibitor U-73122 and by depletion of intracellular Ca(2+) stores but is unaffected by reduction of extracellular Ca(2+) concentration and by blockers of Ca(2+) influx. Therefore, ACh activates PLC and mobilizes Ca(2+) solely from intracellular stores. The calmodulin inhibitors W-7 and calmidazolium attenuate the ACh-induced increase in [Ca(2+)](i) but completely abolish the elevation in CBF. Therefore, elevation of [Ca(2+)](i) is necessary for CBF enhancement but does not lead directly to it. The combined effect of Ca(2+) elevation and of additional factors, presumably mobilized by Ca(2+)-calmodulin, results in a robust CBF enhancement.
Zagoory
O
O
Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
Braiman
A
A
Gheber
L
L
Priel
Z
Z
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D002923:Cilia / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D004947:Esophagus / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D007093:Imidazoles / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D011895:Rana ridibunda; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology
D002147:Calmodulin; D004791:Enzyme Inhibitors; D007093:Imidazoles; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D013449:Sulfonamides; D014268:Trifluoperazine; C031938:calmidazolium; C017967:W 7; D000109:Acetylcholine; D002118:Calcium