title: Involvement of intracellular Ca2+ stores in inhibitory effects of NO donor SIN-1 and cGMP.
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.
authors.affiliation: Department of Internal Medicine II, Technical University of Munich, 81675 Munich, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Franck
authors.forename: M
authors.initials: M
authors.lastname: Storr
authors.forename: A
authors.initials: A
authors.lastname: Puschmann
authors.forename: V
authors.initials: V
authors.lastname: Schusdziarra
authors.forename: H D
authors.initials: HD
authors.lastname: Allescher
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002217:Carbachol / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D007082:Ileum; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D019789:Tetraethylammonium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D007211:Indoles; D010455:Peptides; D015221:Potassium Channels; D013873:Thionucleotides; D018999:Charybdotoxin; D001030:Apamin; C016276:8-bromocyclic GMP; D013779:Tetrodotoxin; D004533:Egtazic Acid; C055656:8-((4-chlorophenyl)thio)cyclic-3',5'-GMP; C002385:linsidomine; D019789:Tetraethylammonium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C064719:iberiotoxin; D000255:Adenosine Triphosphate; D002217:Carbachol; D008981:Molsidomine; D000252:Calcium-Transporting ATPases; D006152:Cyclic GMP; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D005905:Glyburide; D002118:Calcium; C000543:cyclopiazonic acid