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Adrenoceptor‐ and cholinoceptor‐mediated mechanisms in the regulation of 5‐hydroxytryptamine release from isolated tracheae of newborn rabbits
Author(s) -
Freitag Anke,
Wessler Ignaz,
Racké Kurt
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15681.x
Subject(s) - rauwolscine , prazosin , phenylephrine , yohimbine , forskolin , isoprenaline , muscarine , chemistry , endocrinology , medicine , hexamethonium , propranolol , antagonist , receptor , pharmacology , biology , muscarinic acetylcholine receptor , stimulation , blood pressure
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 μ m ) enhanced the outflow of 5‐HT by 80, 290 and 205%, respectively. 5‐HT outflow evoked by 10 μ m phenylephrine was not affected by the presence of the neurotoxin tetrodotoxin (1 μ m ). 3 Rauwolscine, ARC 239 (an α 2B ‐adrenoceptor preferring antagonist), yohimbine and prazosin antagonized the effect of 10 μ m phenylephrine in a concentration‐dependent manner with IC 50 values of 150, 295, 300 and 1,700 nM, respectively. Comparison of the ratios (between all antagonists) of the present IC 50 values with the corresponding ratios of K i values obtained in binding studies for the α 2A ‐, α 2B ‐, α 2C ‐ and α 2D ‐adrenoceptor subtypes strongly suggests the involvement of an α 2B ‐receptor. 4 5‐HT outflow evoked by 10 μ m phenylephrine was inhibited by 65% in the presence of 1 μ m forskolin and abolished in the presence of 10 μ m forskolin. 5 5‐HT outflow evoked by 10 μ m phenylephrine was inhibited by about 45 and 70% in the presence of 0.1 and 1 μ m isoprenaline, respectively. The inhibitory effect of 1 μ m isoprenaline was only marginally antagonized by 1 μ m , but blocked by 10 μ m propranolol. 6 5‐HT outflow was not affected by the muscarine receptor agonist oxotremorine (10 μ m ), but was enhanced by 175% by 100 μ m nicotine. The effect of nicotine was blocked by 100 μ m hexamethonium and prevented by 1 μ m tetrodotoxin or 1 μ m yohimbine. 7 In conclusion, 5‐HT release from NEE cells of the rabbit trachea is stimulated via α‐adrenoceptors most likely of the α 2B ‐subtype localized directly at the NEE cells. Activation of β‐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.