Role of M1 muscarinic receptor subtypes in mediating airway smooth muscle contraction.
Muscarinic receptor subtypes have been identified on airways of several mammalian species, including humans. They are distributed in the lung over submucosal glands, airway ganglia and over the nerves; M1-receptors are found in airway ganglia, M2-receptors (autoreceptors) are present in cholinergic postganglionic nerves at the prejunctional level, whereas the muscarinic receptor subtypes found in airway smooth muscle are of the M3-receptor subtype. We had previously reported the presence of M1-receptors on the smooth muscle of large and small airways of patients suffering from chronic bronchitis, but only is the peripheral airways of healthy subjects; one possible explanation of these results is that the bronchial epithelium may play a role in bronchial responsiveness to relaxant muscarinic antagonists. To clarify this hypothesis we have studied in vitro the responses to acetylcholine (ACh), and some muscarinic selective (pirenzepine, PZ; p-fluorohexahydrosiladyphenidol, pFHHSiD) and non-selective (atropine, ATR) antagonists, on human bronchial smooth muscle in the presence and in the absence of epithelium. The absence of epithelium did not modify the responsiveness to ACh to any great extent and did not change the responsiveness to relaxant antagonists. Our results show that the M1-receptors may play a role in mediating contraction of airway smooth muscle; research is in progress regarding their function in disease.
Matera
M G
MG
Institute of Pharmacology and Toxicology, 1st Faculty of Medicine and Surgery, University of Naples Federico II, Italy.
Cazzola
M
M
Rossi
F
F
D000109:Acetylcholine / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects / Q000502:physiology*; D004848:Epithelium / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D018727:Muscarinic Antagonists; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D010276:Parasympatholytics / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000502:physiology*
D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D010880:Piperidines; D011976:Receptors, Muscarinic; C058297:4-fluorohexahydrosiladifenidol; D010890:Pirenzepine; D001285:Atropine; D000109:Acetylcholine