CHARACTERIZATION OF 5-HYDROXYTUYPTAMINE RELEASE FRONT ISOLATED RABBITAND RAT TRACHEA - THE ROLE OF NEUROENDOCRINE EPITHELIAL-CELLS AND MAST-CELLS

Rabbit or rat isolated tracheae were incubated in vitro, and the relea se of 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindoleace tic acid (5-HIAA) was determined by HPLC with electrochemical detectio n. Release of 5-HT from rabbit tracheae could be evoked by the calcium ionophore A 23187 and, in a calcium-dependent manner, by depolarizing concentrations of potassium (45 mmol/l), but not by the mast cell deg ranulating drug compound 48/80. High potassium- and A 23187-evoked rel ease of 5-HT was markedly higher from tracheae of newborn compared to adult rabbits. In rabbit tracheae, mechanical removal of the mucosa re sulted in 80-90% reduction in tissue 5-HT and in a similar reduction i n high potassium-evoked 5-HT release. 5-Hydroxytryptophan, but not try ptophan, caused a marked increase in the spontaneous outflow of 5-HT a nd 5-HIAA from tracheae of newborn rabbits, and the effect on 5-HT, bu t not that on 5-HIAA, required an intact mucosa. Furthermore, treatmen t with 5-hydroxytryptophan caused an increase in tissue 5-HT and 5-HIA A, and these effects required an intact mucosa. In tracheae of adult r abbits 5-hydroxytryptophan caused similar, although less profound, eff ects. Adrenaline (1 mu mol/l) enhanced the release of 5-HT from newbor n rabbit tracheae, and this effect was inhibited by 1 mu mol/l phentol amine or 1 mu mol/l prazosin, but not affected by 100 nmol/l propranol ol. In rat tracheae, compound 48/80 evoked a large release of 5-HT, wh ereas depolarizing concentrations of potassium (45 mmol/l) had only a very minor effect. In rat tracheae, 5-hydroxytryptophan had small effe cts on the outflow and tissue contents of 5-HT and 5-HIAA in compariso n to the effects on rabbit tracheae; and removal of the mucosa resulte d in only a minor reduction in tissue 5-HT. In conclusion, neuroendocr ine epithelial (NEE) cells and mast cells are the major source of 5-HT in tracheae of the rabbit and rat, respectively. Isolated tracheae of newborn rabbits appear to be a useful model to study 5-HT secretion f rom NEE cells. 5-HT secretion from NEE cells is activated by a rise in intracellular calcium, and calcium influx through voltage-regulated c hannels appears to be one activating pathway. 5-HT secretion from NEE cells can be stimulated via alpha-adrenoceptors.