Cecal dilatation-dislocation is one of the most economically important noninfectious diseases of the GIT in dairy cows, and in Switzerland, the prevalence is the same as for abomasal displacement in dairy cows.1 Clinically, CDD is characterized by reductions in appetite, milk yield, and fecal output and signs of mild colic. Dilatation of the cecum generally precedes dislocation.2–4 However, the exact pathogenesis of the disease has not been elucidated. Originally, it was believed that CDD in cattle was triggered primarily by cecal atony, which would lead to accumulation of gas and digesta and be followed by dilatation and secondary displacement.4,5 However, investigators in a study6 on motility of the cecum and PLAC during the recovery period after surgery for correction of CDD suggested that a motility disturbance, not located in the cecum and PLAC but more distally in the intestine (ie, in the spiral colon), may be implicated in the pathogenesis of the disease.
Serotonin (5-HT) acts via specific receptors in the wall of the GIT to affect motility. Seven families of 5HTRs, termed 5-HTR1 to 5-HTR7, with more than 15 subtypes have been identified. The genetic structure has not been established for all 5-HTR subtypes. The 5-HTR1, 5-HTR2, 5-HTR4, 5-HTR5, 5-HTR6, and 5-HTR7 families are guanine nucleotide binding protein (ie, G protein)–coupled receptors with 7 transmembrane regions, which regulate intracellular signalling through the adenylate cyclase or phopholipase C pathways.7–9 In contrast, 5-HTR3 functions as a ligand-gated ion channel.10
Serotonin receptors are distributed in numerous mammalian tissues, including the brain, the heart, and most segments of the GIT.11–14 The latter contains >80% of the total 5-HT, most of which is in enterochromaffin cells of the intestines but which also is found in enteric neurons.8,15,16 In the intestines, 5-HT acts as a neurotransmitter and as a paracrine-signalling molecule and participates in mucosal sensory transduction.14–17 Of the 5-HTR subtypes identified so far, 5-HTR1A, 5-HTR2A, 5-HTR2B, 5-HTR3, 5-HTR4, and 5-HTR1P primarily modulate GIT motility.8,9,17,18 The various effects induced by 5-HT depend primarily on the 5-HTR involved as well as the species and tissues.19–24
Few investigations have addressed the role of 5-HT in the regulation of GIT motility in ruminants, with most investigations conducted in rodents or humans.8,9,18,25–28 Studies9,29–31 on the pharmacologic aspects of the phasic and tonic motor events in the GIT of ruminants have revealed that cholinergic, adrenergic, serotonergic, opiate, and dopaminergic mechanisms appear to be involved in the regulation of a wide range of physiologic functions. In sheep,32 duodenal distention causes inhibition of forestomach and abomasal motility via 5-HTR1A, 5-HTR2, and 5-HTR3 subtypes. The 5-HTR4 subtype also appears to play an important role in the control of forestomach motility in sheep as well as in the initiation of migrating myoelectric complexes.33,34 Administration of 5-HT inhibits the primary cycles of the reticulorumen in goats35 and sheep.30,36 Furthermore, investigators37 reported a role of 5-HT in the control of forestomach and antroduodenal motility in sheep. Thus, serotonin has several functions in the regulation of cyclic motor events in the GIT of ruminants, but the precise role played by specific 5-HTR subtypes is not known.
The expression of mRNA coding for 5-HTR subtypes in the GIT of healthy dairy cows has been described.38 In that study, investigators reported that relative concentrations of mRNA coding for 5-HTR subtypes vary among receptor subtypes and among locations of the GIT.
The objective of the study reported here was to investigate the expression of mRNA coding for receptor subtypes 5-HTR1A, 5-HTR1B, 5-HTR1D,5-HTR1F, 5-HTR2A, 5-HTR2B, and 5-HTR4 in intestinal tissues of cows with naturally developing CDD, compared with results obtained for healthy dairy cows. We hypothesized that the amount of mRNA coding for 5-HTR subtypes would differ between tissues from healthy dairy cows and cows with a motility disorder leading to CDD. Confirmation of this hypothesis may indicate involvement of 5-HTR subtypes in the pathogenesis of CDD, leading to new perspectives for pharmacologic and therapeutic interventions.
Proximal loop of the ascending colon
External loop of the spiral colon
Maxon 3-0, Tüscher AG, Bern, Switzerland.
RNAlater, Ambion Inc, Austin, Tex.
Mini-beadbeater, Biospec Products, Bartlesville, Okla.
TriFast, PeqLab Biotechnologie GmBh, Erlangen, Germany.
Biophotometer, Eppendorf, Netheler-Hinz, Hamburg, Germany.
Reverse transcriptase, MMLV-RT, Promega, Madison, Wis.
Random hexamer primers, MBI Fermentas, St Leon-Rot, Germany.
Light Cycler Fast Start DNA Master SYBR Green I, Roche Diagnostics, F. Hoffmann la Roche Ltd, Basel, Switzerland.
R 1.8.1, R Foundation for Statistical Computing, Vienna, Austria.
Systat 10.0, Systat Software Inc, Richmond, Calif.
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