Muscarinic M3 receptors mediate contraction of human central and peripheral airway smooth muscle.
The muscarinic receptor subtype involved in human airway smooth muscle contraction was characterised for the first time, using subtype-selective muscarinic antagonists. It was demonstrated that methacholine-induced contraction of central (trachea) and peripheral (small bronchi) airway smooth muscle preparations was antagonised by pirenzepine, AF-DX 116, 4-DAMP methobromide, hexahydrosiladifenidol, and methoctramine with pA2-values characteristic of M3 (smooth muscle/glandular) muscarinic receptors. Since these pA2-values demonstrate significant correlations with those found in bovine and guinea-pig tracheal smooth muscle contraction, it is concluded that these animal tissues provide a good model for the study of M3 subtype-selective muscarinic antagonists to be used as bronchodilators.
Roffel
A F
AF
Department of Pharmacology and Therapeutics, University of Groningen, The Netherlands.
Elzinga
C R
CR
Zaagsma
J
J
D001980:Bronchi / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D009241:Ipratropium / Q000494:pharmacology; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000502:physiology*; D010276:Parasympatholytics / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000502:physiology*; D014132:Trachea / Q000502:physiology*
D010276:Parasympatholytics; D010880:Piperidines; D011976:Receptors, Muscarinic; D010890:Pirenzepine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D009241:Ipratropium; C046773:hexahydrosiladifenidol; C048593:otenzepad