Carbon Monoxide and Nitric Oxide as Examples of the Youngest Class of Transmitters

Nowaczyk, Alicja; Kowalska, Magdalena; Nowaczyk, Jacek; Grześk, Grzegorz

doi:10.3390/ijms22116029

Cited by 33 publications

(36 citation statements)

References 152 publications

(214 reference statements)

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“…Through excitatory motor neurons, ascending interneurons cause contraction of smooth muscle mediated by acetylcholine, substance P, and neurokinin A. Descending interneurons cause smooth muscle relaxation, activating inhibitory motor neurons to release nitric oxide (NO), vasoactive intestinal peptide (VIP), and pituitary adenylate cyclase-activating peptide (PACAP) [ 17 ]. Longitudinal smooth muscles contract and relax in reverse fashion to circular muscle under the regulation of the same neurotransmitters [ 18 , 19 ].…”

Section: Serotonin In the Gi Tractmentioning

confidence: 99%

“…Hagbom showed that serotonin is secreted by EC cells in response to rotavirus enterotoxin NSP4, which acts via 5-HT3 receptor and increases bowel motility [ 77 ]. The mechanism of chemotherapy-dependent nausea is via excitation by anticancer drugs (e.g., cisplatin) of EC cells to release serotonin, which activates 5-HT3 receptors and vagal sensory afferent neurons conduct signals to the emetic center in the brain stem [ 17 , 78 ]. In patients treated by cisplatin, higher urinary levels of 5-HIAA confirmed the correlation with the development of emesis.…”

Section: Serotonin In the Gi Tractmentioning

confidence: 99%

“…Dependent on anticancer drug doses and type, ondansetron combined with dexamethasone gives complete protection from vomiting in up to 70–80% of cases without adverse effects on intestinal activity and stool consistency [ 17 , 80 , 81 ]. Ondansetron was first approved in the EU in 1990 and in the US in 1991.…”

Section: Serotonin In the Gi Tractmentioning

confidence: 99%

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The Role of Serotonin Neurotransmission in Gastrointestinal Tract and Pharmacotherapy

Guzel

Mirowska‐Guzel

2022

Molecules

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5-Hydroxytryptamine (5-HT, serotonin) is a neurotransmitter in both the central nervous system and peripheral structures, acting also as a hormone in platelets. Although its concentration in the gut covers >90% of all organism resources, serotonin is mainly known as a neurotransmitter that takes part in the pathology of mental diseases. Serotonin modulates not only CNS neurons, but also pain transmission and platelet aggregation. In the periphery, 5-HT influences muscle motility in the gut, bronchi, uterus, and vessels directly and through neurons. Serotonin synthesis starts from hydroxylation of orally delivered tryptophan, followed by decarboxylation. Serotonin acts via numerous types of receptors and clinically plays a role in several neural, mental, and other chronic disorders, such as migraine, carcinoid syndrome, and some dysfunctions of the alimentary system. 5-HT acts as a paracrine hormone and growth factor. 5-HT receptors in both the brain and gut are targets for drugs modifying serotonin neurotransmission. The aim of the present article is to review the 5-HT receptors in the gastrointestinal (GI) tract to determine the role of serotonin in GI physiology and pathology, including known GI diseases and the role of serotonin in GI pharmacotherapy.

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Section: Serotonin In the Gi Tractmentioning

confidence: 99%

Section: Serotonin In the Gi Tractmentioning

confidence: 99%

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The Role of Serotonin Neurotransmission in Gastrointestinal Tract and Pharmacotherapy

Guzel

Mirowska‐Guzel

2022

Molecules

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“…Although a significant portion of phenotypic changes caused by nitrite are NO-independent, it is widely accepted that NO is the molecule largely underpinning the physiological influences; nitrite impacts the physiology of living organisms in part by serving as a biochemical circulating reservoir for NO [19]. Additionally, NO can be engaged in cellular physiological and pathological processes through a complex cross-talking with two other gasotransmitters, carbon monoxide (CO) and hydrogen sulfide (H 2 S) [23][24][25][26][27]. Meanwhile, nitrite can be converted back to NO through the one-electronoxidation of NO.…”

Section: Introductionmentioning

confidence: 99%

Complex Interplay of Heme-Copper Oxidases with Nitrite and Nitric Oxide

Chen

Xie

Huang

et al. 2022

IJMS

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Nitrite and nitric oxide (NO), two active and critical nitrogen oxides linking nitrate to dinitrogen gas in the broad nitrogen biogeochemical cycle, are capable of interacting with redox-sensitive proteins. The interactions of both with heme-copper oxidases (HCOs) serve as the foundation not only for the enzymatic interconversion of nitrogen oxides but also for the inhibitory activity. From extensive studies, we now know that NO interacts with HCOs in a rapid and reversible manner, either competing with oxygen or not. During interconversion, a partially reduced heme/copper center reduces the nitrite ion, producing NO with the heme serving as the reductant and the cupric ion providing a Lewis acid interaction with nitrite. The interaction may lead to the formation of either a relatively stable nitrosyl-derivative of the enzyme reduced or a more labile nitrite-derivative of the enzyme oxidized through two different pathways, resulting in enzyme inhibition. Although nitrite and NO show similar biochemical properties, a growing body of evidence suggests that they are largely treated as distinct molecules by bacterial cells. NO seemingly interacts with all hemoproteins indiscriminately, whereas nitrite shows high specificity to HCOs. Moreover, as biologically active molecules and signal molecules, nitrite and NO directly affect the activity of different enzymes and are perceived by completely different sensing systems, respectively, through which they are linked to different biological processes. Further attempts to reconcile this apparent contradiction could open up possible avenues for the application of these nitrogen oxides in a variety of fields, the pharmaceutical industry in particular.

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“…However, it was discovered that in mammals H 2 S has physiological relevance and is endogenously generated [ 1 , 2 ]. Currently, H 2 S is considered to be a member of the class of gasotransmitters or, in other words, endogenous gaseous signaling molecules, along with nitric oxide and carbon monoxide [ 3 , 4 , 5 , 6 , 7 ]. Although still debated, cyanide has also recently been proposed to be part of this class [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of Hydrogen Sulfide on Mitochondrial and Bacterial Bioenergetics

Borisov

Forte

2021

IJMS

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This review focuses on the effects of hydrogen sulfide (H2S) on the unique bioenergetic molecular machines in mitochondria and bacteria—the protein complexes of electron transport chains and associated enzymes. H2S, along with nitric oxide and carbon monoxide, belongs to the class of endogenous gaseous signaling molecules. This compound plays critical roles in physiology and pathophysiology. Enzymes implicated in H2S metabolism and physiological actions are promising targets for novel pharmaceutical agents. The biological effects of H2S are biphasic, changing from cytoprotection to cytotoxicity through increasing the compound concentration. In mammals, H2S enhances the activity of FoF1-ATP (adenosine triphosphate) synthase and lactate dehydrogenase via their S-sulfhydration, thereby stimulating mitochondrial electron transport. H2S serves as an electron donor for the mitochondrial respiratory chain via sulfide quinone oxidoreductase and cytochrome c oxidase at low H2S levels. The latter enzyme is inhibited by high H2S concentrations, resulting in the reversible inhibition of electron transport and ATP production in mitochondria. In the branched respiratory chain of Escherichia coli, H2S inhibits the bo3 terminal oxidase but does not affect the alternative bd-type oxidases. Thus, in E. coli and presumably other bacteria, cytochrome bd permits respiration and cell growth in H2S-rich environments. A complete picture of the impact of H2S on bioenergetics is lacking, but this field is fast-moving, and active ongoing research on this topic will likely shed light on additional, yet unknown biological effects.

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Carbon Monoxide and Nitric Oxide as Examples of the Youngest Class of Transmitters

Cited by 33 publications

References 152 publications

The Role of Serotonin Neurotransmission in Gastrointestinal Tract and Pharmacotherapy

The Role of Serotonin Neurotransmission in Gastrointestinal Tract and Pharmacotherapy

Complex Interplay of Heme-Copper Oxidases with Nitrite and Nitric Oxide

Impact of Hydrogen Sulfide on Mitochondrial and Bacterial Bioenergetics

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