Uptake of 5-hydroxytryptamine by equine digital vein endothelial cells: inhibition by amines found in the equine caecum.
BACKGROUND
5-hydroxytryptamine (5-HT; serotonin) is a potent vasoconstrictor of equine digital blood vessels and has been implicated in the pathogenesis of acute laminitis.


OBJECTIVE
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 micromol/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 micromol/l, which was significantly higher than that of EPVEC (9.9 +/- 2.1 micromol/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 x 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.


CONCLUSIONS
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.
Bailey
S R
SR
Department of Veterinary Basic Sciences, Royal Veterinary College, Royal College Street, London NW1 OTU, UK.
Wheeler-Jones
C
C
Elliott
J
J
D000588:Amines / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002432:Cecum / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005534:Foot Diseases / Q000209:etiology / Q000662:veterinary*; D016166:Free Radical Scavengers; D006724:Hoof and Claw / Q000098:blood supply*; D006734:Horse Diseases / Q000097:blood / Q000209:etiology*; D006736:Horses; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D014316:Tritium; D014661:Vasoconstriction / Q000187:drug effects
D000588:Amines; D016166:Free Radical Scavengers; D012702:Serotonin Antagonists; D014316:Tritium; D012701:Serotonin