title: Nitric oxide in B6 mouse and nitric oxide-sensitive soluble guanylate cyclase in cat modulate acetylcholine release in pontine reticular formation.
abstract: ACh regulates arousal, and the present study was designed to provide insight into the neurochemical mechanisms modulating ACh release in the pontine reticular formation. Nitric oxide (NO)-releasing beads microinjected into the pontine reticular formation of C57BL/6J (B6) mice significantly (P < 0.0001) increased ACh release. Microdialysis delivery of the NO donor N-ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino)-ethanamine (NOC-12) to the mouse pontine reticular formation also caused a concentration-dependent increase in ACh release (P < 0.001). These are the first neurochemical data showing that ACh release in the pontine reticular formation of the B6 mouse is modulated by NO. The signal transduction cascade through which NO modulates ACh release in the pontine reticular formation has not previously been characterized. Therefore, an additional series of studies quantified the effects of a soluble guanylate cyclase (sGC) inhibitor, 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), on ACh release in the cat medial pontine reticular formation. During naturally occurring states of sleep and wakefulness, but not anesthesia, ODQ caused a significant (P < 0.001) decrease in ACh release. These results show for the first time that NO modulates ACh in the medial pontine reticular formation of the cat via an NO-sensitive sGC signal transduction cascade. Isoflurane and halothane anesthesia have been shown to decrease ACh release in the medial pontine reticular formation. The finding that ODQ did not alter ACh release during isoflurane or halothane anesthesia demonstrates that these anesthetics disrupt the NO-sensitive sGC-cGMP pathway. Considered together, results from the mouse and cat indicate that NO modulates ACh release in arousal-promoting regions of the pontine reticular formation via an NO-sensitive sGC-cGMP pathway.
authors.affiliation: Department of Anesthesiology, University of Michigan, Ann Arbor, MI 48109-0615, USA. rlydic@umich.edu
authors.forename: Ralph
authors.initials: R
authors.lastname: Lydic
authors.forename: Ricardo
authors.initials: R
authors.lastname: Garza-Grande
authors.forename: Richard
authors.initials: R
authors.lastname: Struthers
authors.forename: Helen A
authors.initials: HA
authors.lastname: Baghdoyan
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001143:Arousal / Q000502:physiology*; D002415:Cats; D017869:Cyclic GMP-Dependent Protein Kinases / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology*; D009603:Nitroso Compounds / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D011149:Pons / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D012890:Sleep / Q000502:physiology; D013997:Time Factors
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; C118603:NOC 12; D009603:Nitroso Compounds; D010069:Oxadiazoles; D011810:Quinoxalines; D009569:Nitric Oxide; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D000109:Acetylcholine