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

摘要: 1. Isolated tracheae of newborn rabbits were incubated in vitro and the outflow 5-hydroxytryptamine (5-HT) was determined by h.p.l.c. with electrochemical detection. Evidence has previously been provided that this 5-HT derives from neuroendocrine epithelial (NEE) cells airway mucosa. 2. Phenylephrine (1, 10 30 microM) enhanced 80, 290 205%, respectively. evoked microM phenylephrine not affected presence neurotoxin tetrodotoxin (1 microM). 3. Rauwolscine, ARC 239 (an alpha(2B)-adrenoceptor preferring antagonist), yohimbine prazosin antagonized effect a concentration-dependent manner IC50 values 150, 295, 300 1,700 nM, Comparison ratios (between all antagonists) present corresponding Ki obtained binding studies for alpha(2A)-, alpha(2B)-, alpha(2C)- alpha(2D)-adrenoceptor subtypes strongly suggests involvement an alpha(2B)-receptor. 4. inhibited 65% 1 forskolin abolished forskolin. 5. about 45 70% 0.1 isoprenaline, The inhibitory isoprenaline only marginally microM, but blocked propranolol. 6. muscarine receptor agonist oxotremorine (10 microM), 175% 100 nicotine. nicotine hexamethonium prevented or yohimbine. 7. In conclusion, release NEE rabbit trachea is stimulated via alpha-adrenoceptors most likely alpha(2B)-subtype localized directly at cells. Activation beta-adrenoceptors as well direct activation adenylyl cyclase exert effects on release. nicotinic, muscarinic receptors, also evokes 5-HT. However, appears to be mediated indirectly noradrenaline.