title: Carbon monoxide and nitric oxide interactions in magnocellular neurosecretory neurones during water deprivation.
abstract: Nitric oxide (NO) and carbon monoxide (CO) are diffusible gas messengers in the brain. Previously, we have shown their independent involvement in central fluid/electrolyte homeostasis control. In the present study, we investigated a possible functional interaction between NO/CO in the regulation of vasopressin (VP) and oxytocin (OT) magnocellular neurosecretory cells (MNCs) activity in euhydrated (EU) and dehydrated [48-h water-deprived (48WD)] rats. Using brain slices from EU and 48WD rats, we measured, by immunohistochemistry, the expression of neuronal NO synthase (nNOS, which synthesises NO) and haeme-oxygenase (HO-1, which synthesises CO) in the hypothalamic supraoptic nucleus (SON). In addition, we used patch-clamp electrophysiology to investigate whether regulation of SON MNC firing activity by endogenous CO was dependent on NO bioavailability and GABAergic inhibitory synaptic function. We found a proportion of OT and VP SON MNCs in EU rats to co-express both of HO-1 and nNOS (33.2 ± 2.9% and 15.3 ± 1.4%, respectively), which was increased in 48WD rats (55.5 ± 0.9% and 21.0 ± 1.7%, respectively, P < 0.05 for both). Inhibition of endogenous HO activity [chromium mesoporphyrin IX chloride (CrMP) 20 μm] induced MNC membrane hyperpolarisation and decreased firing activity, and these effects were blunted by previous blockade of endogenous NOS activity (l-NAME, 2 mm) or blockade of inhibitory GABA function [Picrotoxin (Sigma-Aldrich, St Louis, MO, USA), 50 μm]. No significant changes in SON NO bioavailability (4,5 diaminofluorescein diacetate fluorescence) were observed after CrMP treatment. Taken together, our results support a state-dependent functional inter-relationship between NO and CO in MNCs, in which CO acts as an excitatory gas molecule, whose effects are largely dependent on interactions with the inhibitory SON signals NO and GABA.
authors.affiliation: Department of Physiology, Georgia Regents University, Augusta, GA, USA; Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
authors.forename: W L
authors.initials: WL
authors.lastname: Reis
authors.forename: V C
authors.initials: VC
authors.lastname: Biancardi
authors.forename: S
authors.initials: S
authors.lastname: Son
authors.forename: J
authors.initials: J
authors.lastname: Antunes-Rodrigues
authors.forename: J E
authors.initials: JE
authors.lastname: Stern
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D010121:Oxytocin / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013495:Supraoptic Nucleus / Q000166:cytology / Q000378:metabolism*; D014667:Vasopressins / Q000378:metabolism; D014868:Water Deprivation / Q000502:physiology*
chemical_list: D014667:Vasopressins; D009569:Nitric Oxide; D010121:Oxytocin; D002248:Carbon Monoxide; D052248:Nitric Oxide Synthase Type I; D006419:Heme Oxygenase (Decyclizing)
keywords: carbon monoxide; nitric oxide; osmotic stimulation; oxytocin; vasopressin