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Construction of cell lines expressing the human somatostatin receptors SSTR1 and SSTR4

Construction of cell lines expressing the human somatostatin...

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第十五届国际药理学大会

作者： Sandor Zoltan Kvell Krisztian Czompoly Tamas janos szolcsanyi Dept.Pharmacology Univ.PecsHungary Dept.Biotechnology Univ.PecsHungary Dept.Biotechnology Univ.PecsHungary Dept.Pharmacology Univ.PecsHungary

＜正＞ The peptide hormone somatostatin has been shown to inhibit the release of inflammatory neuropeptides from the nerve endings of capsaicin sensitive neurons and thus prevent inflammation. Previous studies indicated that somatostatin exerts its anti-inflammatory effects through the SSTR4 and possibly the SSTR1 receptor. To facilitate large scale screening for pharmacologically active compounds acting on these targets, two new cell lines were created which express the human SSTR1 and SSTR4 receptors. CHO-K1 cells were transfected by alentiviral system containing the human SSTR1 and SSTR4 cDNAs. In the constructs the SSTR cDNA is followedby an internal ribosome entry site allowing separate expression of the enhanced green fluorescent protein from the same mRNA. Stable and uniform expression of the SSTR receptors were demonstrated by RT-PCR. flow cytometry and immunohistochemistry. Binding of somatostatin-14. somatostatin analogue peptid TT-232. the selective SSTR4 ligand KD-5621 and the selective SSTR1 ligand KD-7825 were demonstrated by a radioactive binding assay.

关键词： cell line somatostatin SSTR1 SSTR4

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ROLE OF TRPV1 RECEPTORS IN BLEOMYCIN-INDUCED SCLERO-DERMA IN MICE

ROLE OF TRPV1 RECEPTORS IN BLEOMYCIN-INDUCED SCLERO-DERMA IN...

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第十五届国际药理学大会

作者： Szabo Arpad Czirjak Laszlo Helyes Zsuzsanna Laszlo Terezia Elekes Krisztian Starr Anna Brain Susan szolcsanyi janos Pinter Erika Dept.of Pharmacology University of PecsHungary Dept.of Immunology and Rheumatology University of PecsHungary Dept.of Pharmacology University of PecsHungary Dept.of Phatology University of PecsHungary Dept.of Pharmacology University of PecsHungary Centre of Cardiovascular Biology and Medicine Kings CollegeUK Centre of Cardiovascular Biology and Medicine Kings CollegeUK Dept.of Pharmacology University of PecsHungary Dept.of Pharmacology University of PecsHungary

＜正＞ Neuropeptides released from the activated capsaicin-sensitive. TRPV1 receptor-expressing sensory nerves modulate inflammatory processes. This study examines the role of TRPV1 and calcitonin-gene related peptide（ CGRP） in bleomycin-induced scleroderma using transgenic *** sclerosis of TRPV1 receptor and CGRP gene-deficient mice （TRPV1-/-and CGRP-/-） and their wild-type （WT） counterparts was induced by daily s. c. bleomycin injection during 30 days. Composite histological sclerosis score was calculated on the basis of thickening, leukocyte infiltration and amount of collagen boundles. The collagen-specific amino-acid, hydroxyproline. in the skin was measured with spectrophotometry. Quantitative real-time RT-PCR was used to determine type Ⅰ collagen-alpha mRNA. Bleomycin induced a marked skin thickening and fibrosis. Both sclerosis score and hydroxyproline content of the skin were significantly increased in TRPV1-/-and CGRP-/-mice compared to WT animals. Type Ⅰ collagenalpha mRNA was significantly higher in bleomycin-treated TRPV1-/-mice. These data suggest that CGRP released by TRPV1 activation exerts a protective action against fibrosis.

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Anti-inflammatory effects of somatostatin receptor subtype 4 selective agonist J-2156 in rodents

Anti-inflammatory effects of somatostatin receptor subtype 4...

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第十五届国际药理学大会

作者： Pinter Erika Helyes Zsuzsanna Nemeth Jozsef Sandor Katalin Elekes Krisztian Szabo Arpad Pozsgai Gabor Engstrom Ma Wurster Siegfried Keszthelyi Daniel szolcsanyi janos Dept. of Pharmacol. University of Pecs Hungary Dept. of Pharmacol. University of Pecs Hungary Dept. of Pharmacol. University of Pecs Hungary Dept. of Pharmacol. University of Pecs Hungary Dept. of Pharmacol. University of Pecs Hungary Dept. of Pharmacol. University of Pecs Hungary Dept. of Pharmacol. University of Pecs Hungary Juvantia Pharma Ltd. Turku Finland Juvantia Pharma Ltd. Turku Finland Dept. of Pharmacol.University of Pecs Hungary Dept. of Pharmacol.University of Pecs Hungary

＜正＞ The aim of the present study was to investigate a,sst4 selective synthetic agonist, J- 2156,on sensory neuropeptide release and acute inflammatory processes. Electrically - induced release of substance P,calcitonin gene - related peptide and somatostatin from isolated rat tracheae was measured with radioimmunoassay. Mustard oil - induced neurogenic inflammation in the rat hindpaw skin was determined by Evans blue accumulation and in the mouseear with a micrometer. Dextran -carrageenan - induced non - neurogenic inflammation was measured by *** accumulation evoked by IL - 1 beta or zymosan in the murine back skin was determined with myeloperoxidase assay.J - 2156 （10 - 2000 nM） concentration- dependently diminished neuropeptide release. It also inhibited neurogenic and non - neurogenic acute inflammatory processes but did not influence IL - 1 beta or zymosan - induced leukocyte accumulation. These results suggest that J - 2156 acting on sst4 inhibits neuropeptide release and vascular components of inflammation therefore opens new way in antiinflammatory treatment.

关键词： somatostatin sst4 receptor neuropeptides inflammation

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