title: Modulation of neuronal nitric oxide release by soluble guanylyl cyclase in guinea pig colon.
abstract: Peripheral autonomic neurones release nitric oxide (NO) upon nerve activation. However, the regulation of neuronal NO formation is poorly understood. We used the cyclic guanosine 3',5'-monophosphate (cGMP) analogue 8-Br-cGMP, the soluble guanylyl cyclase (sGC) stimulator YC-1, the phosphodiesterase inhibitor zaprinast and the sGC inhibitor ODQ to study whether the sGC/cGMP pathway is involved in regulation of neuronal NO release in nerve plexus-containing smooth muscle preparations from guinea pig colon. Electrical stimulation of the preparation evoked release of NO/NO(-)(2). In the presence of 8-Br-cGMP, YC-1 and zaprinast (all at 10(-4) M) the NO/NO(-)(2)-release increased to 152 +/- 16% (P < 0.05), 164 +/- 37% (P < 0.05) and 290 +/- 67% (P < 0.05) of controls, respectively. Conversely, ODQ (10(-5) M) decreased the evoked release of NO/NO(-)(2) to 49 +/- 7% (P < 0.05) of controls. Our data suggest that the sGC/cGMP pathway modulates NO release. Thus it is likely that NO exerts a positive feedback on its own release from peripheral autonomic neurones.
authors.affiliation: Department of Urology, Karolinska Hospital, Stockholm, 171 76, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Hallén
authors.forename: C
authors.initials: C
authors.lastname: Olgart
authors.forename: L E
authors.initials: LE
authors.lastname: Gustafsson
authors.forename: N P
authors.initials: NP
authors.lastname: Wiklund
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003106:Colon / Q000201:enzymology*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004594:Electrophysiology; D004791:Enzyme Inhibitors; D006162:Guanylate Cyclase / Q000378:metabolism*; D006168:Guinea Pigs; D007150:Immunohistochemistry; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D009474:Neurons / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D010069:Oxadiazoles / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D010726:Phosphodiesterase Inhibitors; D011688:Purinones; D011810:Quinoxalines; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D001120:Arginine; D006162:Guanylate Cyclase; C011145:zaprinast; D006152:Cyclic GMP; D004121:Dimethyl Sulfoxide