Proliferative effect of acetylcholine on rat trachea epithelial cells is mediated by nicotinic receptors and muscarinic receptors of the M1-subtype.
Acetylcholine (ACh), synthesized in mammalian non-neuronal cells such as epithelial cells of the airways, digestive tract and skin, is involved in the regulation of basic cell functions (so-called non-neuronal cholinergic system). In the present experiments rat trachea epithelial cells have been cultured to study the proliferative effect of applied ACh by [3H]thymidine incorporation. ACh (exposure time 24 h) caused a concentration-dependent increase in cell proliferation with a doubling of the [3H]thymidine incorporation at a concentration of 0.1 microM. This effect was partly reduced by 30 microM tubocurarine and completely abolished by the additional application of 1 microM atropine. The stimulatory effect of acetylcholine, remaining in the presence of tubocurarine, was prevented by 1 microM pirenzepine (preferentially acting at M1-receptors), but neither by 1 microM AFDX 116 (preferentially acting at M2-receptors) nor by 1 microM hexahydrosiladifenidol (preferentially acting at M3-receptors). The combination of tubocurarine and pirenzepine halved the basal [3H]thymidine incorporation. In conclusion, ACh produces a proliferative effect in rat trachea epithelial cells, the effect being mediated by both nicotinic receptors and muscarinic receptors of the M1-subtype.
Metzen
Jürgen
J
Institute of Pharmacology, University of Mainz, Obere Zahlbacher Str 67, D-55101, Mainz, Germany.
Bittinger
Fernando
F
Kirkpatrick
Charles James
CJ
Kilbinger
Heinz
H
Wessler
Ignaz
I
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects*; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D013936:Thymidine / Q000378:metabolism; D014132:Trachea / Q000166:cytology / Q000187:drug effects*; D014403:Tubocurarine / Q000494:pharmacology
D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D000109:Acetylcholine; D013936:Thymidine; D014403:Tubocurarine