0000000000437537

AUTHOR

Anke Freitag

Adrenoceptor- and cholinoceptor-mediated mechanisms in the regulation of 5-hydroxytryptamine release from isolated tracheae of newborn rabbits

Abstract 1. Isolated tracheae of newborn rabbits were incubated in vitro and the outflow of 5-hydroxytryptamine (5-HT) was determined by h.p.l.c. with electrochemical detection. Evidence has previously been provided that this 5-HT outflow derives from neuroendocrine epithelial (NEE) cells of the airway mucosa. 2. Phenylephrine (1, 10 and 30 microM) enhanced the outflow of 5-HT by 80, 290 and 205%, respectively. 5-HT outflow evoked by 10 microM phenylephrine was not affected by the presence of the neurotoxin tetrodotoxin (1 microM). 3. Rauwolscine, ARC 239 (an alpha(2B)-adrenoceptor preferring antagonist), yohimbine and prazosin antagonized the effect of 10 microM phenylephrine in a concentr…

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Characterization of 5-hydroxytryptamine release from isolated rabbit and rat trachea: the role of neuroendocrine epithelial 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 …

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Nitric oxide, via activation of guanylyl cyclase, suppresses alpha2-adrenoceptor-mediated 5-hydroxytryptamine release from neuroendocrine epithelial cells of rabbit tracheae.

Isolated tracheae of newborn rabbits were incubated in vitro and the outflow of 5-hydroxytryptamine (5-HT) was determined by HPLC with electrochemical detection. Evidence has previously been provided that this 5-HT outflow derives from neuroendocrine epithelial (NEE) cells of the airway mucosa. Phenylephrine, at a maximally effective concentration of 10 microM, caused a transient increase in 5-HT outflow by about 250%, an effect mediated by alpha2B-adrenoceptors, as previously shown. The phenylephrine-induced 5-HT release remained unchanged in calcium-free medium, but was reduced by 75% when the tracheae were incubated in calcium-free medium which contained 0.5 mM EDTA, a treatment known to…

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Phosphodiesterase inhibitors suppress alpha2-adrenoceptor-mediated 5-hydroxytryptamine release from tracheae of newborn rabbits.

The outflow of 5-hydroxytryptamine (5-HT) from isolated tracheae of newborn rabbits was determined by high pressure liquid chromatography with electrochemical detection. This 5-HT outflow reflects release from neuroendocrine epithelial cells of the airway mucosa, as previously shown. Phenylephrine, via alpha2B-adrenoceptors, caused a transient increase in 5-HT outflow, maximally by about 250%, an effect mediated by liberation of intracellular Ca2+, as previously shown. The non-selective phosphodiesterase inhibitor 2-isobutyl-1-methylxanthine (IBMX) concentration-dependently inhibited phenylephrine-induced 5-HT release (completely at 100 microM, IC50: 1.3 microM). Likewise, benzafentrine (in…

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Effects of bacterial lipopolysaccharides (LPS) and tumour necrosis factor-alpha (TNF alpha) on rat tracheal epithelial cells in culture: morphology, proliferation and induction of nitric oxide (NO) synthase.

Rat tracheal epithelial cells were cultured and the effects of LPS and TNF alpha on cell morphology, rate of proliferation and NO synthase activity were studied. NO synthase activity was determined by measuring the accumulation of 3H-L-citrulline during incubation of confluent monolayer with 3H-L-arginine. In untreated cells no significant 3H-L-citrulline formation was detected, and bradykinin and the calcium ionophore A 23187 failed to stimulate 3H-L-citrulline formation excluding a constitutively expressed, calcium-dependent NO synthase activity. After culturing the cells for 18 h in the presence of LPS (10 micrograms/ml) and TNF alpha (500 U/ml) a marked formation of 3H-L-citrulline coul…

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