326 EQUINE VETERINARY JOURNAL Equine vet. J. (2008) 40 (4) 326-331 doi: 10.2746/042516408X293583 Summary Reasons for performing study: Increased plasma (5-HT) concentrations are reported in horses predisposed to develop laminitis and after i.v. infusion of endotoxins. In the equine jejunum contractile 5-HT 1A -like receptors show tachyphylaxia upon prolonged activation with 5-HT. Therefore, increased systemic 5-HT release in colic horses could play a possible role in the pathophysiology of ileus. Objective: To investigate possible increased systemic release of 5-HT in colic horses with compromised bowel and to identify the source of 5-HT overload. Methods: Concentrations of 5-HT were determined in plasma and peritoneal fluid (PF) of healthy horses (n = 10), strangulating small intestinal colic horses (n = 18), nonsurgical colic horses (n = 10) and cryptorchid stallions (n = 6). It was attempted to identify the source of 5-HT overload by comparing the blood and PF 5-HT concentrations within horses and by assessing the in vivo platelet activation through determination of the β-thromboglobulin (β-TG)/platelet factor 4 (PF4) ratio. Results: All horses in the strangulating small intestinal colic group had plasma (P = 0.006) and PF (P = 0.01) 5-HT concentrations above those found in the control group. Plasma β-TG/PF4 ratio in these horses exceeded 2 in all cases, indicating in vivo platelet activation. Concentrations of 5-HT in PF of colic horses with compromised bowel were significantly lower than the corresponding plasma concentrations (P = 0.005). Potential relevance: In horses with compromised bowel, significant amounts of 5-HT can be released into the systemic circulation, through massive release of platelet-stored 5-HT. 5-HT is a very potent proinflammatory, vasoconstrictive and immunomodulatory agent. In view of the rapid and prolonged tachyphylaxia, shown for the jejunal 5-HT 1A -like receptors, this increased systemic 5-HT release could play a role in the pathophysiology of ileus in horses. Introduction Serotonin (5-hydroxytryptamine, 5-HT) is a very important messenger in the digestive tract; it is essential to the brain-gut connection and related to gastrointestinal motility and visceral sensation. Contractile 5-HT receptors have been identified in several parts of the equine GI tract (Sellers et al. 1985; Nieto et al. 2000; Weiss et al. 2002; Delesalle et al. 2006, 2008; Delco et al. 2007) and also in the equine digital circulation (Bailey et al. 1998). Bailey et al. (2003a) demonstrated seasonal changes in plasma concentrations of caecum-derived amines, among which was 5-HT, in clinically normal ponies and ponies predisposed to laminitis. They suggested that the release of 5-HT into the systemic circulation may contribute to haemodynamic disturbances in horses and ponies with acute laminitis (Elliott and Bailey 2006). Menzies-Gow et al. (2004) measured increased concentrations of plasma thromboxane β 2 and 5-HT in horses, following experimental endotoxaemia. The 5-HT 1A serotonergic receptor subtype, identified in the equine small intestine, is responsible for the 5-HT induced contractile response (Delesalle et al. 2006, 2007a). It is known for its features of tachyphylaxia (receptor desensitisation), which takes place when the receptor is protractedly and excessively activated in the presence of an overload of agonist such as endogenous 5-HT (Raymond et al. 1999; Serres et al. 2000; Hensler and Durgam 2001). Release of excessive amounts of 5-HT in colic horses, could therefore play a role in the pathophysiology of ileus (Delesalle et al. 2006). In the body, 5-HT is stored in blood platelets and in the enterochromaffin (EC) cells of the GI tract. These cells are found in the mucosal epithelium of the whole GI tract of many vertebrates, including the horse (Fink et al. 2006). Taking into consideration 2 important features, predominantly found in colic horses predisposed to develop ileus, namely intestinal necrosis and endotoxaemia, both platelets and EC cells of necrotising bowel segments, could serve as a source of 5-HT overload in colic horses (Koenig and Cote 2006). The aim of this study was to determine the 5-HT concentrations in blood and peritoneal fluid (PF) of Determination of the source of increased serotonin (5-HT) concentrations in blood and peritoneal fluid of colic horses with compromised bowel C. DELESALLE*, G. R. VAN DE WALLE † , C. NOLTEN ‡ , L. VER DONCK ‡ , A. VAN HEMELRIJCK ‡ , W. DRINKENBURG ‡ , H. DE BOSSCHERE § , P. CLAES # , P. DEPREZ, L. LEFERE, S. TORFS and R. A. LEFEBVRE ¶ Large Animal Internal Medicine, Faculty of Veterinary Medicine, Ghent University, Merelbeke; † Laboratory for Thrombosis Research, K.U. Leuven Campus Kortrijk, Kortrijk; ‡ Johnson & Johnson Pharmaceutical Research and Development, Beerse; § Medical Laboratory Bruyland, Meiweg 1a, B-8500 Kortrijk; # HistoGeneX NV, Campus Middelheim, Antwerp; and ¶ Heymans Institute of Pharmacology, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium. Keywords: horse; disseminated intravascular coagulation (DIC); β-thromboglobulin; platelet factor 4 (PF-4); endotoxaemia *Author to whom correspondence should be addressed. [Paper received for publication 21.12.07; Accepted 07.02.08]