Anti‐inflammatory effect of synthetic somatostatin analogues in the rat

Helyes, Zsuzsanna; Pintér, Erika; Németh, József; Kéri, Gÿorgý; Thán, Márta; Oroszi, Gábor; Horváth, Anikó; Szolcsányi, Janós

doi:10.1038/sj.bjp.0704396

Cited by 97 publications

(68 citation statements)

References 35 publications

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“…The amount of the accumulated Evans blue was expressed as mg of dye/g of wet tissue. 27) Isolation of Rat Neutrophils Blood was collected in heparinized tubes. A 6% dextran solution was added to the blood and the supernatant was collected after 1 h. The equal parts of Lymphoprep TM and the supernatant were mixed.…”

Section: Methodsmentioning

confidence: 99%

.ALPHA.1-Acid Glycoprotein Suppresses Rat Acute Inflammatory Paw Edema through the Inhibition of Neutrophils Activation and Prostaglandin E2 Generation

Matsumoto

Nishi

Kikuchi

et al. 2007

Biological & Pharmaceutical Bulletin

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Section: Methodsmentioning

confidence: 99%

.ALPHA.1-Acid Glycoprotein Suppresses Rat Acute Inflammatory Paw Edema through the Inhibition of Neutrophils Activation and Prostaglandin E2 Generation

Matsumoto

Nishi

Kikuchi

et al. 2007

Biological & Pharmaceutical Bulletin

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“…Direct evidence for the involvement of somatostatin of neural origin in the observed antiinflammatory and analgesic actions was also provided (1-3, 8, 9). Results obtained with synthetic somatostatin receptor agonists suggested that these inhibitory effects were mediated by receptors of the SRIF 2 family (sst 4 /sst 1 ) (8,11,15,16,(19)(20)(21)25). However, because of the lack of sst 4 -selective antagonists, the precise receptor mechanisms of the somatostatin-mediated ''sensocrine'' inhibitory actions on inflammation and nociception have remained to be elucidated until the generation of sst 4 receptor gene-deficient mice.…”

Section: Figmentioning

confidence: 99%

“…4). Several data indicate that receptors in the SRIF 1 group mediate the endocrine and antiproliferative effects, whereas the SRIF 2 group, predominantly the sst 4 receptor, is responsible for the anti-inflammatory and antinociceptive actions (3,15,16).…”

mentioning

confidence: 99%

Impaired defense mechanism against inflammation, hyperalgesia, and airway hyperreactivity in somatostatin 4 receptor gene-deleted mice

Helyes

Pintér

Sándor

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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We have shown that somatostatin released from activated capsaicin-sensitive nociceptive nerve endings during inflammatory processes elicits systemic anti-inflammatory and analgesic effects. With the help of somatostatin receptor subtype 4 gene-deleted mice (sst4 ؊/؊ ), we provide here several lines of evidence that this receptor has a protective role in a variety of inflammatory disease models; several symptoms are more severe in the sst4 knockout animals than in their wild-type counterparts. Acute carrageenaninduced paw edema and mechanical hyperalgesia, inflammatory pain in the early phase of adjuvant-evoked chronic arthritis, and oxazolone-induced delayed-type hypersensitivity reaction in the skin are much greater in mice lacking the sst 4 receptor. Airway inflammation and consequent bronchial hyperreactivity elicited by intranasal lipopolysaccharide administration are also markedly enhanced in sst 4 knockouts, including increased perivascular/peribronchial edema, neutrophil/macrophage infiltration, mucus-producing goblet cell hyperplasia, myeloperoxidase activity, and IL-1␤, TNF-␣, and IFN-␥ expression in the inflamed lung. It is concluded that during these inflammatory conditions the released somatostatin has pronounced counterregulatory effects through sst4 receptor activation. Thus, this receptor is a promising novel target for developing anti-inflammatory, analgesic, and anti-asthmatic drugs.allergic contact dermatitis ͉ arthritis ͉ capsaicin-sensitive afferents ͉ endotoxin-induced pneumonitis ͉ inflammatory cytokines

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“…throughout the experimental period of 18 days dose-dependently inhibits oedema and inflammatory mechanical hyperalgesia (Pinter et al 2002). Octreotide had also no such effect in mustard oil-induced neurogenic inflammatory models, where TT-232 was proved to be highly effective (Helyes et al 2001). Therefore, we presume that SSTR4 -and less importantly also SSTR1 -mediated signalling is responsible for the anti-inflammatory action of somatostatin and TT-232.…”

Section: Sstr4 and Sstr1 Play An Important Role In The In Vivo Anti-imentioning

confidence: 83%

TT-232: An Anti-tumour and Anti-inflammatory Peptide Therapeutic in Clinical Development

Kéri¹,

Schwab

Szokolóczi

et al. 2005

Int J Pept Res Ther

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TT-232 is a structural derivative of the peptide hormone somatostatin with selective antiproliferative and anti-inflammatory properties. It has a strong anti-tumour activity both in vitro and in vivo on a wide range of tumour models and induces apoptosis. Its anti-tumour activity is mediated through the SSTR1 receptor and by the tumour specific isoform of pyruvate kinase. TT-232 has been shown to be a potent neurogenic inflammation inhibitory, anti-inflammatory and analgesic agent with a broader spectrum than presently available antiinflammatory/analgesic drugs. In animal models it is effective against neurogenic inflammation and blocks neuropathic hyperalgesia where COX-1 or COX-2 inhibitors (e.g. diclofenac or meloxicam) proved ineffective. TT-232 has passed phase I clinical trials without toxicity and significant side effects. Human phase II efficacy studies are ongoing in melanoma indication. Two more oncological indications and phase II clinical trials in inflammatory diseases, including rheumatoid arthritis and burn injuries are in preparation. This compound has the perspective to become the first drug in molecularly targeted therapy of inflammation where a combined effect of anti-inflammatory, analgesic and neurogenic inflammation inhibiting activity can be achieved.

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Anti‐inflammatory effect of synthetic somatostatin analogues in the rat

Cited by 97 publications

References 35 publications

.ALPHA.1-Acid Glycoprotein Suppresses Rat Acute Inflammatory Paw Edema through the Inhibition of Neutrophils Activation and Prostaglandin E2 Generation

.ALPHA.1-Acid Glycoprotein Suppresses Rat Acute Inflammatory Paw Edema through the Inhibition of Neutrophils Activation and Prostaglandin E2 Generation

Impaired defense mechanism against inflammation, hyperalgesia, and airway hyperreactivity in somatostatin 4 receptor gene-deleted mice

TT-232: An Anti-tumour and Anti-inflammatory Peptide Therapeutic in Clinical Development

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