Multiple muscarinic receptor subtypes mediating pulmonary oedema in the rabbit.
The effects of various muscarinic antagonists on acetylcholine (ACh)-induced pulmonary oedema were studied in isolated perfused rabbit lungs. ACh induced a dose-dependent increase in the capillary filtration coefficient (Kf,c). This effect has been previously related to the activation of the capsaicin-sensitive nerve fibres and the release of substance P. Atropine, pirenzepine (M1-selective antagonist) and 4-DAMP (M3-selective antagonist) altered this response, producing a dose-dependent shift to the right of the ACh concentration-Kf,c response curve. By contrast, the M2-selective antagonist AFDX-116 shifted the ACh concentration-response curve to the left. Atropine, pirenzepine and 4-DAMP also significantly reduced the capsaicin-induced increase in the Kf,c, while AFDX-116 enhanced it. We conclude that multiple muscarinic receptor subtypes are present in the rabbit lung, located on the C-fibres, and are involved in the ACh-induced pulmonary oedema. M1 and M3 receptors seem to stimulate the release of neuropeptides from C-fibres, whereas M2 receptors have an inhibitory effect on these fibers.
Delaunois
A
A
Department of Pharmacology-Toxicology-Pharmacotherapy, Faculty of Veterinary Medicine, University of Liège, Belgium.
Gustin
P
P
Ansay
M
M
D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D002211:Capsaicin; D005260:Female; D008168:Lung / Q000294:innervation; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009412:Nerve Fibers / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D011654:Pulmonary Edema / Q000139:chemically induced / Q000503:physiopathology*; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000145:classification* / Q000502:physiology*
D018727:Muscarinic Antagonists; D009479:Neuropeptides; D011976:Receptors, Muscarinic; D000109:Acetylcholine; D002211:Capsaicin