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. 4 5-HT outflow evoked by 10 IM phenylephrine was inhibited by 65% in the presence of 1 gM forskolin and abolished in the presence of 10 gM forskolin. 5 5-HT outflow evoked by 10 gM phenylephrine was inhibited by about 45 and 70% in the presence of 0.1 and 1 gM isoprenaline, respectively. The inhibitory effect of 1 gM isoprenaline was only marginally antagonized by 1 gM, but blocked by 10 gM propranolol.6 5-HT outflow was not affected by the muscarine receptor agonist oxotremorine (10 gM), but was enhanced by 175% by 100 gM nicotine. The effect of nicotine was blocked by 100 gM hexamethonium and prevented by 1 gM tetrodotoxin or 1 gM yohimbine. 7 In conclusion, 5-HT release from NEE cells of the rabbit trachea is stimulated via a-adrenoceptors most likely of the a2B-subtype localized directly at the NEE cells. Activation of ,B-adrenoceptors as well as direct activation of adenylyl cyclase by forskolin exert inhibitory effects on 5-HT release. Activation of nicotinic, but not of muscarinic receptors, also evokes the release of 5-HT. However, the effect of nicotine appears to be mediated indirectly via the release of noradrenaline.

Role of 5‐HT2A, 5‐HT4 and 5‐HT7 receptors in the antigen‐induced airway hyperresponsiveness in guinea‐pigs

“…Interestingly, we found that the nicotinic receptor was colocalized in the same cells in which 5-HT was observed, which is in agreement with a published study performed in hamster lungs [38]. Other research groups have already reported that stimulation of the nicotinic receptor by nicotine induces the release of 5-HT from PNECs [30,39]. In our study, PNECs might be a potential source of 5-HT, at least in sensitized guinea-pigs, from which 5-HT release may be triggered by ACh during a dose-response curve.…”

Functional and pharmacological mechanisms of nucleoside transport across the basolateral membrane of rabbit tracheal epithelial cells

“…The existence of various cell surface receptors in the upper airway that modulate levels of intracellular second messengers is well characterized. The co-administration of various catecholamines of adrenergic receptor agonists, that act through elevating intracellular cAMP levels, can potentially enhance the absorption of inhaled nucleoside analogues (Freitag et al, 1996). On the other hand, the presence of muscarinic, cholinergic receptor antagonists, that prevents the elevation of [Ca 2+ ] i , can add up to the same outcome if included in similar pulmonary formulations of nucleoside drugs (Reinheimer et al, 2000).…”