Regulation of slow wave frequency by IP(3)-sensitive calcium release in the murine small intestine.
Slow waves determine frequency and propagation characteristics of contractions in the small intestine, yet little is known about mechanisms of slow wave regulation. We propose a role for intracellular Ca(2+), inositol 1,4,5,-trisphosphate (IP(3))-sensitive Ca(2+) release, and sarcoplasmic reticulum (SR) Ca(2+) content in the regulation of slow wave frequency because 1) 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM, a cytosolic Ca(2+) chelator, reduced the frequency or abolished the slow waves; 2) thapsigargin and cyclopiazonic acid (CPA), inhibitors of SR Ca(2+)-ATPase, decreased slow wave frequency; 3) xestospongin C, a reversible, membrane-permeable blocker of IP(3)-induced Ca(2+) release, abolished slow wave activity; 4) caffeine and phospholipase C inhibitors (U-73122, neomycin, and 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate) inhibited slow wave frequency; 5) in the presence of CPA or thapsigargin, stimulation of IP(3) synthesis with carbachol, norepinephrine, or phenylephrine acting on alpha(1)-adrenoceptors initially increased slow wave frequency but thereafter increased the rate of frequency decline, 6) thimerosal, a sensitizing agent of IP(3) receptors increased slow wave frequency, and 7) ryanodine, a selective modulator of Ca(2+)-induced Ca(2+) release, had no effect on slow wave frequency. In summary, these data are consistent with a role of IP(3)-sensitive Ca(2+) release and the rate of SR Ca(2+) refilling in regulation of intestinal slow wave frequency.
Malysz
J
J
Intestinal Disease Research Program and Department of Medicine, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
Donnelly
G
G
Huizinga
J D
JD
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002614:Chelating Agents / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D007424:Intracellular Fluid / Q000378:metabolism; D047028:Macrocyclic Compounds; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009599:Nitroprusside / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D015398:Signal Transduction / Q000187:drug effects; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D000316:Adrenergic alpha-Agonists; D015220:Calcium Channels; D002614:Chelating Agents; D018679:Cholinergic Agonists; D004791:Enzyme Inhibitors; D053496:Inositol 1,4,5-Trisphosphate Receptors; D047028:Macrocyclic Compounds; D010080:Oxazoles; D018160:Receptors, Cytoplasmic and Nuclear; C108644:xestospongin A; D009599:Nitroprusside; D005576:Colforsin; D002110:Caffeine; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium