Surgery and sepsis increase somatostatin-like immunoreactivity in the human plasma

Sütő, Balázs; Bagoly, Teréz; Börzsei, Rita; Lengl, Orsolya; Szolcsányi, Janós; Németh, Timea; Loibl, Csaba; Bardonicsek, Zsofia; Pintér, Erika; Helyes, Zsuzsanna

doi:10.1016/j.peptides.2010.03.018

Cited by 9 publications

(10 citation statements)

References 24 publications

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“…SOM release might be due to opening of TRPA1 or TRPV1 channels (Pethő et al, 2017; Pozsgai et al, 2017). Elevated SOM plasma concentration in response to painful disease was detected in rodents and patients (Helyes et al, 2004; Antal et al, 2008; Suto et al, 2010). SOM possesses systemic antinociceptive and anti-inflammatory properties mediated by sst 4 receptors (Helyes et al, 2004; Pintér et al, 2006; Schuelert et al, 2015; Pozsgai et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

TRPA1 Ion Channel Determines Beneficial and Detrimental Effects of GYY4137 in Murine Serum-Transfer Arthritis

et al. 2019

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Modulation of nociception and inflammation by sulfide in rheumatoid arthritis and activation of transient receptor potential ankyrin 1 (TRPA1) ion channels by sulfide compounds are well documented. The present study aims to investigate TRPA1-mediated effects of sulfide donor GYY4137 in K/BxN serum-transfer arthritis, a rodent model of rheumatoid arthritis. TRPA1 and somatostatin sst4 receptor wild-type (WT) and knockout mice underwent K/BxN serum transfer and were treated daily with GYY4137. Functional and biochemical signs of inflammation were recorded, together with histological characterization. These included detection of hind paw mechanical hyperalgesia by dynamic plantar esthesiometry, hind paw volume by plethysmometry, and upside-down hanging time to failure. Hind paw erythema, edema, and passive movement range of tibiotarsal joints were scored. Somatostatin release from sensory nerve endings of TRPA1 wild-type and knockout mice in response to polysulfide was detected by radioimmunoassay. Polysulfide formation from GYY4137 was uncovered by cold cyanolysis. GYY4137 aggravated mechanical hyperalgesia in TRPA1 knockout mice but ameliorated it in wild-type ones. Arthritis score was lowered by GYY4137 in TRPA1 wild-type animals. Increased myeloperoxidase activity, plasma extravasation, and subcutaneous MIP-2 levels of hind paws were detected in TRPA1 knockout mice upon GYY4137 treatment. Genetic lack of sst4 receptors did not alter mechanical hyperalgesia, edema formation, hanging performance, arthritis score, plasma extravasation, or myeloperoxidase activity. TRPA1 WT animals exhibited smaller cartilage destruction upon GYY4137 administration. Sodium polysulfide caused TRPA1-dependent somatostatin release from murine nerve endings. Sulfide released from GYY4137 is readily converted into polysulfide by hypochlorite. Polysulfide potently activates human TRPA1 receptors expressed in Chinese hamster ovary (CHO) cells. According to our data, the protective effect of GYY4137 is mediated by TRPA1, while detrimental actions are independent of the ion channel in the K/BxN serum-transfer arthritis model in mice. At acidic pH in inflamed tissue sulfide is released from GYY4137 and reacts with neutrophil-derived hypochlorite. Resulting polysulfide might be responsible for TRPA1-mediated antinociceptive and anti-inflammatory as well as TRPA1-independent pro-inflammatory effects.

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Section: Discussionmentioning

confidence: 99%

TRPA1 Ion Channel Determines Beneficial and Detrimental Effects of GYY4137 in Murine Serum-Transfer Arthritis

et al. 2019

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“…Beside a population of nociceptors SOM is expressed in the central nervous system and peripheral tissues, too ( 23 , 38 ). Treatment with TRPA1 receptor agonists or nociceptor activation by other means leads to SOM release from primary sensory neurons and the peptide reaches significant concentration in the bloodstream ( 9 , 39 – 42 ). SOM exerts antinociceptive and anti-inflammatory effects at parts of the body distant from the site of release.…”

Section: Discussionmentioning

confidence: 99%

Role of Transient Receptor Potential Ankyrin 1 Ion Channel and Somatostatin sst4 Receptor in the Antinociceptive and Anti-inflammatory Effects of Sodium Polysulfide and Dimethyl Trisulfide

et al. 2018

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Transient receptor potential ankyrin 1 (TRPA1) non-selective ligand-gated cation channels are mostly expressed in primary sensory neurons. Polysulfides (POLYs) are Janus-faced substances interacting with numerous target proteins and associated with both protective and detrimental processes. Activation of TRPA1 in sensory neurons, consequent somatostatin (SOM) liberation and action on sst4 receptors have recently emerged as mediators of the antinociceptive effect of organic trisulfide dimethyl trisulfide (DMTS). In the frame of the present study, we set out to compare the participation of this mechanism in antinociceptive and anti-inflammatory effects of inorganic sodium POLY and DMTS in carrageenan-evoked hind-paw inflammation. Inflammation of murine hind paws was induced by intraplantar injection of carrageenan (3% in 30 µL saline). Animals were treated intraperitoneally with POLY (17 µmol/kg) or DMTS (250 µmol/kg) or their respective vehicles 30 min prior paw challenge and six times afterward every 60 min. Mechanical pain threshold and swelling of the paws were measured by dynamic plantar aesthesiometry and plethysmometry at 2, 4, and 6 h after initiation of inflammation. Myeloperoxidase (MPO) activity in the hind paws were detected 6 h after challenge by luminescent imaging. Mice genetically lacking TRPA1 ion channels, sst4 receptors and their wild-type counterparts were used to examine the participation of these proteins in POLY and DMTS effects. POLY counteracted carrageenan-evoked mechanical hyperalgesia in a TRPA1 and sst4 receptor-dependent manner. POLY did not influence paw swelling and MPO activity. DMTS ameliorated all examined inflammatory parameters. Mitigation of mechanical hyperalgesia and paw swelling by DMTS were mediated through sst4 receptors. These effects were present in TRPA1 knockout animals, too. DMTS inhibited MPO activity with no participation of the sensory neuron–SOM axis. While antinociceptive effects of POLY are transmitted by activation of peptidergic nerves via TRPA1, release of SOM and its effect on sst4 receptors, those of DMTS partially rely on SOM release triggered by other routes. SOM is responsible for the inhibition of paw swelling by DMTS, but TRPA1 does not contribute to its release. Modulation of MPO activity by DMTS is independent of TRPA1 and sst4.

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“…Routine urine analysis was also performed. Blood samples were also collected for measuring vasoactive sensory neuropeptides, such as PACAP-38 and somatostatin by specific and sensitive radioimmunoassay (RIA) techniques developed in our laboratory [ 30 , 31 ]. Peptidase inhibitor aprotinin (200 IU per ml of blood; Gordox, Gedeon Richter, Budapest) was added immediately to the blood taken into EDTA tubes.…”

Section: Methodsmentioning

confidence: 99%

Impairment of microcirculation and vascular responsiveness in adolescents with primary Raynaud phenomenon

2018

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Background Raynaud’s phenomenon (RP) is a functional vascular disease, presenting with recurrent episodes of ischemia of extremities in response to cold and emotional stress. Investigating cutaneous microcirculation is an important tool in understanding the complex neuro-immuno-vascular interactions in its pathophysiological mechanisms. Since there is no available data on vascular responsiveness in RP in the paediatric population, we investigated skin perfusion and heat-induced hyperaemia in comparison with clinical severity and laboratory parameters of the disease.MethodsFifty two adolescents (27 patients with primary RP and 25 age-matched healthy controls) were investigated in the study. Patients were divided into two groups according to the symptoms existing within the previous 2 months. Following baseline microcirculation measurement with Laser Doppler flowmetry (Periflux 5000 system), all subjects underwent local heating test at 42 °C and 44 °C. Besides routine laboratory parameters, immune-serological tests and the vasoactive sensory neuropeptides somatostatin and pituitary adenylate-cyclase activating polypeptide (PACAP) were measured.ResultsBaseline perfusion measured in perfusion units (PU) at 32 °C was significantly lower in symptomatic RP patients (97.6 ± 22.4 PU) compared with both healthy volunteers (248.3 ± 23.5 PU, p < 0.001) and RP patients without symptoms (187.4 ± 24.9 PU, p < 0.05). After local heating to 42 °C maximum blood flow was significantly reduced in primary RP participants with current symptoms (358.6 ± 43.9 PU, p < 0.001), but not in asymptomatic ones (482.3 ± 28.7 PU, p > 0.05) when compared with healthy subjects (555.9 ± 28.2 PU). Both the area under the response curve and the latency to reach the maximum flow were significantly increased in both RP groups (symptomatic 164.6 ± 7.4 s, p < 0.001, asymptomatic 236.4 ± 17.4 s, p < 0.001) when compared with the control group (101.9 ± 4.7 s). The heat-induced percentage increase from baseline to maximal blood flow was significantly greater in symptomatic RP adolescents in comparison with healthy ones. Laboratory parameters and neuropeptide plasma levels were not altered in any groups.ConclusionTo our knowledge this is the first study in paediatric population to show altered heat-induced cutaneous hyperaemia responses in relation with the clinical severity and symptomatology.

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Surgery and sepsis increase somatostatin-like immunoreactivity in the human plasma

Cited by 9 publications

References 24 publications

TRPA1 Ion Channel Determines Beneficial and Detrimental Effects of GYY4137 in Murine Serum-Transfer Arthritis

TRPA1 Ion Channel Determines Beneficial and Detrimental Effects of GYY4137 in Murine Serum-Transfer Arthritis

Role of Transient Receptor Potential Ankyrin 1 Ion Channel and Somatostatin sst4 Receptor in the Antinociceptive and Anti-inflammatory Effects of Sodium Polysulfide and Dimethyl Trisulfide

Impairment of microcirculation and vascular responsiveness in adolescents with primary Raynaud phenomenon

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