Inhibition of electrical slow waves and Ca2+ currents of gastric and colonic smooth muscle by phosphatase inhibitors.
The effects of calyculin A, a phosphatase inhibitor isolated from the marine sponge Discodermia calyx, on the electrical activity of colonic and gastric muscles were studied. Calyculin A reduced the amplitude and duration of slow waves, primarily by inhibiting the plateau component. Okadaic acid, another phosphatase inhibitor, also reduced the amplitude and duration of gastric slow waves. The mechanism of action of calyculin A was investigated by studying its effects on inward currents of isolated gastric and colonic myocytes. Calyculin A reduced the amplitude of the peak and the sustained components of the inward current. Okadaic acid had similar effects. These data suggest that phosphorylation of Ca2+ channels of gastrointestinal smooth muscles may inhibit Ca2+ currents. This mechanism may provide an important means of regulating the currents responsible for excitation-contraction coupling in these muscles.
Ward
S M
SM
Department of Physiology, University of Nevada School of Medicine, Reno 89557.
Vogalis
F
F
Blondfield
D P
DP
Ozaki
H
H
Fusetani
N
N
Uemura
D
D
Publicover
N G
NG
Sanders
K M
KM
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004285:Dogs; D004594:Electrophysiology; D004988:Ethers, Cyclic / Q000494:pharmacology; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008387:Marine Toxins; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D019319:Okadaic Acid; D010080:Oxazoles / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D013270:Stomach / Q000187:drug effects / Q000201:enzymology
D015220:Calcium Channels; D004988:Ethers, Cyclic; D008387:Marine Toxins; D010080:Oxazoles; D019319:Okadaic Acid; C059041:calyculin A; D010749:Phosphoprotein Phosphatases