title: Comparison of the anti-inflammatory and anti-nociceptive effects of cortistatin-14 and somatostatin-14 in distinct in vitro and in vivo model systems.
abstract: We showed that somatostatin (SST) exerts anti-inflammatory and anti-nociceptive effects through somatostatin receptor subtypes 4 and 1 (sst(4)/sst(1)). Since cortistatin (CST) is a structurally similar peptide, we aimed at comparing the sst(1)- and sst(4)-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 sst(1) and sst(4)-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.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, Szigeti str. 12, 7624, Pécs, Hungary.
authors.forename: Adrienn
authors.initials: A
authors.lastname: Markovics
authors.forename: Éva
authors.initials: É
authors.lastname: Szoke
authors.forename: Katalin
authors.initials: K
authors.lastname: Sándor
authors.forename: Rita
authors.initials: R
authors.lastname: Börzsei
authors.forename: Teréz
authors.initials: T
authors.lastname: Bagoly
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Kemény
authors.forename: Krisztián
authors.initials: K
authors.lastname: Elekes
authors.forename: Erika
authors.initials: E
authors.lastname: Pintér
authors.forename: János
authors.initials: J
authors.lastname: Szolcsányi
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Helyes
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016466:CHO Cells; D006224:Cricetinae; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D020078:Neurogenic Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D009479:Neuropeptides / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000494:pharmacology*
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D009479:Neuropeptides; D010456:Peptides, Cyclic; C467796:cortistatin 14; D013004:Somatostatin