Characterization of 5-hydroxytryptamine release from isolated rabbit and rat trachea: the role of neuroendocrine epithelia cells and mast cells.

Rabbit or rat isolated tracheae were incubated in vitro, and the release of 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) was determined by HPLC with electrochemical detection. 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 degranulating drug compound 48/80. High potassium- and A 23187-evoked release of 5-HT was markedly higher from tracheae of newborn compared to adult rabbits. In rabbit tracheae, mechanical removal of the mucosa resulted in 80-90% reduction in tissue 5-HT and in a similar reduction in high potassium-evoked 5-HT release. 5-Hydroxytryptophan, but not tryptophan, caused a marked increase in the spontaneous outflow of 5-HT and 5-HIAA from tracheae of newborn rabbits, and the effect on 5-HT, but not that on 5-HIAA, required an intact mucosa. Furthermore, treatment with 5-hydroxytryptophan caused an increase in tissue 5-HT and 5-HIAA, and these effects required an intact mucosa. In tracheae of adult rabbits 5-hydroxytryptophan caused similar, although less profound, effects. Adrenaline (1 micromol/1) enhanced the release of 5-HT from newborn rabbit tracheae, and this effect was inhibited by 1 micro mol/l phentolamine or 1 micromol/1 prazosin, but not affected by 100 nmol/1 propranolol. In rat tracheae, compound 48/80 evoked a large release of 5-HT, whereas depolarizing concentrations of potassium (45 mmol/1) had only a very minor effect. In rat tracheae, 5-hydroxytryptophan had small effects on the outflow and tissue contents of 5-HT and 5-HIAA in comparison to the effects on rabbit tracheae; and removal of the mucosa resulted in only a minor reduction in tissue 5-HT. In conclusion, neuroendocrine 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 from NEE cells. 5-HT secretion from NEE cells is activated by a rise in intracellular calcium, and calcium influx through voltage-regulated channels appears to be one activating pathway. 5-HT secretion from NEE cells can be stimulated via alpha-adrenoceptors.