註釋 ABSTRACT DISTRIBUTION OF NEUROKININ 2 AND 3 RECEPTOR mRNA IN THE NORMAL EQUINE GASTROINTESTINAL TRACT AND EFFECT OF INFLAMMATION ON EXPRESSION OF NEUROKININ 1, 2 AND 3 RECEPTOR mRNA IN THE JEJUNUM Dr. Christina E. W. Martin Advisor: Dr. Judith B. Koenig This study is an investigation of the distribution of neurokinin receptors in the equine gastrointestinal tract. The objectives of this research were to determine the relative distribution of neurokinin 2 (NK2) and 3 (NK3) receptor mRNA in the normal equine gastrointestinal tract, and also to determine changes in neurokinin 1 (NK1), NK2 and NK3 receptor mRNA expression after ischemia/reperfusion injury or intraluminal distension in the jejunum. Samples from 9 regions in the gastrointestinal tract (duodenum, jejunum, ileum, caecum, right ventral colon, left ventral colon, pelvic flexure, right dorsal colon and left dorsal colon) were harvested from 5 mature healthy horses, euthanized for reasons unrelated to the gastrointestinal tract, for the study of NK2 and NK3 mRNA distribution in the normal intestinal tract. To evaluate the effect of inflammation on NK1, NK2 and NK3 receptor mRNA distribution, samples were taken from 6 horses whose jejunum underwent one of three treatments: control (sham-operated), intraluminal distension (ILD) or ischemic strangulation obstruction and subsequent reperfusion injury (ISO). NK2 and NK3 receptor primers were designed and real-time PCR was used to quantify NK1 (primers previously described), NK2 and NK3 receptor mRNA expression in the treatment groups described above. In healthy horses, NK2 mRNA expression in the small intestine was highest in the duodenum and lowest in the ileum. NK2 mRNA expression in the large intestine was highest in the caecum. NK3 mRNA expression was more variable between individuals than NK2 expression overall. No significant difference was found between concentrations of NK1 or NK3 receptor mRNA between control, ILD or ISO treatments. A trend was noted for NK1 mRNA to be lower in ILD treatments than control. For NK2 receptor mRNA, ILD and ISO values were significantly lower than that of control. Tachykinin agonists and antagonists have shown therapeutic value in intestinal inflammation and motility disorders in laboratory animals and humans. Neurokinin receptor mRNA is present in the equine intestinal tract. Relative levels appear to be altered by inflammation, although the clinical significance of this finding needs to be further evaluated. The current study suggests that tachykinin therapy may have a potential utility in the medical treatment of equine post-operative ileus and equine colic, however further investigation into the physiology of neurokinin receptors in the horse is warranted. 