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Comparison of the Anti-inflammatory and Anti-nociceptive Effects of Cortistatin-14 and Somatostatin-14 in Distinct In Vitro and In Vivo Model Systems

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Abstract

We showed that somatostatin (SST) exerts anti-inflammatory and anti-nociceptive effects through somatostatin receptor subtypes 4 and 1 (sst4/sst1). Since cortistatin (CST) is a structurally similar peptide, we aimed at comparing the sst1- and sst4-binding and activating abilities, as well as the effects of SST-14 and CST-14 on inflammatory and nociceptive processes. CST-14 concentration-dependently displaced radiolabeled SST-14 binding, induced similar sst1 and sst4-activation with a less potency, and exerted significantly greater inhibitory effect on endotoxin-stimulated interleukin (IL)-1β production of murine peritoneal macrophages. Capsaicin-induced calcitonin gene-related peptide release from peripheral sensory nerve terminals of isolated rat tracheae was significantly decreased by 2 μM CST and 100 nM SST, but concentration-response correlation was not found. Mustard oil-evoked acute neurogenic plasma protein extravasation in the rat hindpaw skin, carrageenan-induced mouse paw edema, mechanical hyperalgesia, and IL-1β, tumor necrosis factor-α production, as well as mild heat injury-evoked thermal hyperalgesia were similarly attenuated by both peptides. In the latter case, i.pl. and i.p. injections exerted equal inhibitory actions. CST-14 and SST-14 similarly diminish both acute neurogenic and cellular inflammatory processes, as well as mechanical and heat hyperalgesia, in which their inhibitory effect on sensory nerve endings is likely to be involved. However, CST-14 exerts remarkably greater inhibition on cytokine production.

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Acknowledgments

This work was supported by OTKA K73044, K78059, and K81984; ETT 03-380/2009 and ETT 04-364/2009; the “Science, Please! Research Teams on Innovation” program (SROP-4.2.2/08/1/2008-0011); and the Developing Competitiveness of Universities in the South Transdanubian Region (SROP-4.2.1.B-10/2/KONV-2010-0002). The Ph.D. fellowship of Adrienn Markovics was supported by Sanofi-Aventis/Chinoin.

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  1. Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, Szigeti str. 12, 7624, Pécs, Hungary

    Adrienn Markovics, Éva Szőke, Katalin Sándor, Rita Börzsei, Teréz Bagoly, Ágnes Kemény, Krisztián Elekes, Erika Pintér, János Szolcsányi & Zsuzsanna Helyes

  2. PharmInVivo Ltd., Szondi Gy. str. 10, 7269, Pécs, Hungary

    Erika Pintér, János Szolcsányi & Zsuzsanna Helyes

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  1. Adrienn Markovics
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  2. Éva Szőke
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  10. Zsuzsanna Helyes
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Correspondence to Zsuzsanna Helyes.

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Markovics, A., Szőke, É., Sándor, K. et al. Comparison of the Anti-inflammatory and Anti-nociceptive Effects of Cortistatin-14 and Somatostatin-14 in Distinct In Vitro and In Vivo Model Systems. J Mol Neurosci 46, 40–50 (2012). https://doi.org/10.1007/s12031-011-9577-4

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