Role of acetylcholine and muscarinic receptors in serotonin-induced bronchoconstriction in the mouse.
For the murine trachea, it has been reported that constriction evoked by serotonin (5-HT) is largely dependent on acetylcholine (ACh) released from the epithelium, owing to the sensitivity of the 5-HT response to epithelium removal, sensitivity to atropine, and insensitivity to tetrodotoxin (Moffatt et al., 2003). Consistent with this assumption, the respiratory epithelium contains ACh, its synthesizing enzyme, and the high-affinity choline transporter CHT1 (Reinheimer et al., 1996; Pfeil et al., 2003; Proskocil et al., 2004). Recently, we demonstrated that ACh can be released from non-neuronal cells by corticosteroid-sensitive polyspecific organic cation transporters (OCTs), which are also expressed by airway epithelial cells (Lips et al., 2005). Hence, we proposed that 5-HT evokes release of ACh from epithelial cells via OCTs and that this epithelial-derived ACh induces bronchoconstriction. We tested this hypothesis in a well-established model of videomorphometric analysis of bronchial diameter in precision-cut murine lung slices utilizing epithelium removal to assess the role of the epithelium, OCT mouse knockout (KO) strains to assess the role of OCT isoforms, and muscarinic receptor M2/M3 double-KO mice to assess the cholinergic component of 5-HT induced bronchoconstriction, as bronchi of this strain are entirely unresponsive to cholinergic stimulation(Struckmann et al., 2003).
Kummer
Wolfgang
W
Institute for Anatomy and Cell Biology, JLU, 35385 Giessen, Germany. Wolfgang.Kummer@anatomie.med.uni-giessen.de
Wiegand
Silke
S
Akinci
Sibel
S
Schinkel
Alfred H
AH
Wess
Jürgen
J
Koepsell
Hermann
H
Haberberger
Rainer Viktor
RV
Lips
Katrin Susanne
KS
D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D003345:Corticosterone / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*
D011976:Receptors, Muscarinic; D012701:Serotonin; D000109:Acetylcholine; D003345:Corticosterone