Abstract
We investigated the role of K+ channels and intracellular Ca2+ stores in the relaxations induced by the NO donor 3-morpholinosydnonimine (SIN-1) and 8-bromo-cGMP (8-BrcGMP), 8-(4-chlorophenylthio)-cGMP (pCPT-cGMP), and alpha, beta-methylene-ATP in isolated segments of rat ileum. The inhibitory responses to SIN-1 and the cGMP analogs were not influenced by the K+ blockers apamin, charybdotoxin, iberiotoxin, or glibenclamide, whereas relaxations induced by alpha,beta-methylene-ATP were abolished by apamin and tetraethylammonium. The NO-donor SIN-1 and the cGMP analogs were able to inhibit contractions induced by activation of L-type Ca2+ channels (BAY-K-8644), by carbachol (CCh), and by cyclopiazonic acid (CPA), a blocker of sarcoplasmic Ca2+-ATPase. However, the inhibition of the combined CPA and CCh response was reduced and the dose-response curve of SIN-1 shifted to the right. Intracellular Ca2+ stores were emptied by incubation in Ca2+-free buffer and repetitive stimulation with CCh or BAY-K-8644. After restoration of extracellular Ca2+, the inhibitory effect of SIN-1 and pCPT-cGMP was only attenuated, whereas in the additional presence of CPA, the inhibitory effect of SIN-1 was blocked and the effect of 8-BrcGMP reduced. Thus depleting intracellular Ca2+ stores attenuated the effect of SIN-1 and 8-BrcGMP, suggesting an involvement of functional Ca2+ stores.
MeSH terms
-
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
-
Adenosine Triphosphate / analogs & derivatives
-
Adenosine Triphosphate / pharmacology
-
Animals
-
Apamin / pharmacology
-
Calcium / metabolism*
-
Calcium Channel Blockers / pharmacology
-
Calcium-Transporting ATPases / antagonists & inhibitors
-
Carbachol / pharmacology
-
Charybdotoxin / pharmacology
-
Cyclic GMP / analogs & derivatives*
-
Cyclic GMP / metabolism*
-
Cyclic GMP / pharmacology
-
Egtazic Acid / pharmacology
-
Glyburide / pharmacology
-
Ileum
-
In Vitro Techniques
-
Indoles / pharmacology
-
Kinetics
-
Male
-
Molsidomine / analogs & derivatives*
-
Molsidomine / pharmacology
-
Muscle Contraction / drug effects
-
Muscle Contraction / physiology*
-
Muscle, Smooth / drug effects
-
Muscle, Smooth / physiology*
-
Peptides / pharmacology
-
Potassium Channels / drug effects
-
Potassium Channels / physiology*
-
Rats
-
Rats, Wistar
-
Tetraethylammonium / pharmacology
-
Tetrodotoxin / pharmacology
-
Thionucleotides / pharmacology*
Substances
-
Calcium Channel Blockers
-
Indoles
-
Peptides
-
Potassium Channels
-
Thionucleotides
-
Charybdotoxin
-
Apamin
-
8-bromocyclic GMP
-
Tetrodotoxin
-
Egtazic Acid
-
8-((4-chlorophenyl)thio)cyclic-3',5'-GMP
-
linsidomine
-
Tetraethylammonium
-
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
-
iberiotoxin
-
Adenosine Triphosphate
-
Carbachol
-
Molsidomine
-
Calcium-Transporting ATPases
-
Cyclic GMP
-
alpha,beta-methyleneadenosine 5'-triphosphate
-
Glyburide
-
Calcium
-
cyclopiazonic acid