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Summary Reasons for performing study: 5‐hydroxytryptamine (5‐HT; serotonin) is a potent vasoconstrictor of equine digital blood vessels and has been implicated in the pathogenesis of acute laminitis. Objectives: The aims of this study were firstly to examine whether cells of the digital blood vessel wall exhibited an active uptake mechanism for 5‐HT and to characterise its efficiency; and secondly, to study the potential inhibitory effect on this process of other amines, produced in the equine caecum. Methods: Confluent monolayers of equine digital vein endothelial cells (EDVEC) and equine digital vein smooth muscle cells (EDVSMC) were incubated with (3H)5‐HT (0.1–250 μmol/l) and the total and active uptake calculated. Equine pulmonary vein endothelial cells (EPVEC) were used as a positive control. Results: Both EDVEC and EDVSMC showed uptake of (3H)5‐HT by nonfaci litated diffusion; however, only EDVEC showed evidence of saturable facilitated uptake mechanism, with a Km of 41.6 ± 9.3 μmol/l, which was significantly higher than that of EPVEC (9.9 ± 2.1 μmol/l). All 6 caecally‐derived amines examined (tyramine, spermine, isoamylamine, tryptamine, phenylethylamine and isobutylamine) inhibited the total uptake of (3H)5‐HT in a concentration‐dependent manner, tyramine having the lowest IC50 (3.7 × 10−6 mol/l). Conclusions: These data suggest that facilitated uptake into the endothelium could play a role in moderating the vasoconstrictor response to 5‐HT in the equine digital circulation. Potential clinical relevance: The vasoconstrictor action of 5‐HT could be potentiated by gut‐derived amines, providing a feasible link between GI disturbances and the pathophysiology of laminits.
Equine Veterinary Journal – Wiley
Published: Mar 1, 2003
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