Abstract
Circular smooth muscle strips isolated from cat gastric fundus were studied in order to understand whether the sarcoplasmic reticulum (SR) and SR Ca2+-ATPase could play a role in the regulation of the muscle tone. Cyclopiazonic acid (CPA), a specific inhibitor of SR Ca2+-ATPase, caused a significant and sustained increase in muscle tone, depending on the presence of extracellular Ca2+. Nifedipine and cinnarizin only partially suppressed the CPA-induced tonic contraction. Bay K 8644 antagonized the relaxant effect of nifedipine in CPA-contracted fundus. Nitric-oxide-releasing agents sodium nitroprusside and 3-morpholino-sydnonimine completely suppressed the CPA-induced tonic contraction. The blockers of Ca2+-activated K+ channels, tetraethylammonium, charybdotoxin and/or apamin, decreased the contractile effect of CPA. Vanadate increased the tone but did not change significantly the effect of CPA. CPA exerted its contractile effect even when Ca2+ influx was triggered through the Na+/Ca2+ exchanger and the other Ca2+ entry pathways were blocked. Thapsigargin, another specific SR Ca2+-ATPase inhibitor, also increased the muscle tone. The effect of thapsigargin was completely suppressed by sodium nitroprusside and 3-morpholino-sydnonimine and partially by nifedipine. In conclusion, under conditions when the SR Ca2+-ATPase is inhibited, the tissue develops a strong tonic contraction and a large part of this is mediated by Ca2+ influx presumably via nifedipine-sensitive Ca2+ channels. This study suggests the important role of SR Ca2+-ATPase in the modulation of the muscle tone and the function of SR as a "buffer barrier" to Ca2+ entry in the cat gastric fundus smooth muscle.
MeSH Terms
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester/pharmacology
Animals
Apamin/pharmacology
Calcium Channel Agonists/pharmacology
Calcium Channel Blockers/pharmacology
Calcium-Transporting ATPases/antagonists & inhibitors,physiology
Cats
Cinnarizine/pharmacology
Enzyme Inhibitors/pharmacology
Gastric Fundus/drug effects,enzymology,physiology
In Vitro Techniques
Indoles/pharmacology
Male
Molsidomine/analogs & derivatives,pharmacology
Muscle Contraction/drug effects,physiology
Muscle, Smooth/drug effects,enzymology,physiology
Nifedipine/pharmacology
Nitroprusside/pharmacology
Potassium Channel Blockers
Sarcoplasmic Reticulum/drug effects,enzymology,physiology
Thapsigargin/pharmacology
Chemicals
Calcium Channel Agonists
Calcium Channel Blockers
Enzyme Inhibitors
Indoles
Potassium Channel Blockers
Nitroprusside
Apamin
Cinnarizine
linsidomine
Thapsigargin
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
Molsidomine
Calcium-Transporting ATPases
Nifedipine
cyclopiazonic acid
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Petkov G V
Institute of Biophysics, Bulgarian Academy of Sciences, Acad. G. Bonchev Street., Bl. 21, 1113-Sofia, Bulgaria.
Boev K K
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