title: Inhibition of carbachol-evoked oscillatory currents by the NO donor sodium nitroprusside in guinea-pig ileal myocytes.
abstract: The effect of sodium nitroprusside (SNP) on carbachol (CCh)-evoked inward cationic current (Icat) oscillations in guinea-pig ileal longitudinal myocytes was investigated using the whole-cell patch-clamp technique and permeabilized longitudinal muscle strips. SNP (10 microm) completely inhibited I(cat) oscillations evoked by 1 microm CCh. 1H-(1,2,4) Oxadiazole [4,3-a] quinoxaline-1-one (ODQ; 1 microm) almost completely prevented the inhibitory effect of SNP on Icat oscillations. 8-Bromo-guanosine 3',5'-cyclic monophosphate (8-Br-cGMP; 30 microm) in the pipette solution completely abolished Icat oscillations. However, a pipette solution containing Rp-8-Br-cGMP (30 microm) almost completely abolished the inhibitory effect of SNP on Icat oscillations. When the intracellular calcium concentration ([Ca2+]i) was held at a resting level using BAPTA (10 mm) and Ca2+ (4.6 microm) in the pipette solution, CCh (1 microm) evoked only the sustained component of Icat without any oscillations and SNP did not affect the current. A high concentration of inositol 1,4,5-trisphosphate (IP3; 30 microm) in the patch pipette solutions significantly reduced the inhibitory effect of SNP (10 microm) on Icat oscillations. SNP significantly inhibited the Ca2+ release evoked by either CCh or IP3 but not by caffeine in permeabilized preparations of longitudinal muscle strips. These results suggest that the inhibitory effects of SNP on Icat oscillations are mediated, in part, by functional modulation of the IP3 receptor, and not by the inhibition of cationic channels themselves or by muscarinic receptors in the plasma membrane. This inhibition seems to be mediated by an increased cGMP concentration in a protein kinase G-dependent manner.
authors.affiliation: Department of Physiology, College of Medicine, Yonsei University 134, Shinchon-Dong, Seodaemun-Gu, Seoul 120-752, Republic of Korea.
authors.forename: Seung-Soo
authors.initials: SS
authors.lastname: Chung
authors.forename: Duck-Sun
authors.initials: DS
authors.lastname: Ahn
authors.forename: Hong-Ghi
authors.initials: HG
authors.lastname: Lee
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Lee
authors.forename: Taick-Sang
authors.initials: TS
authors.lastname: Nam
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002217:Carbachol / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000502:physiology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D010069:Oxadiazoles / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D019869:Phosphatidylinositol 3-Kinases / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D010738:Type C Phospholipases / Q000494:pharmacology
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D002614:Chelating Agents; D018721:Muscarinic Agonists; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D010726:Phosphodiesterase Inhibitors; D011810:Quinoxalines; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D002110:Caffeine; D004533:Egtazic Acid; D002217:Carbachol; D019869:Phosphatidylinositol 3-Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D010738:Type C Phospholipases; D006152:Cyclic GMP; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid