MULTIPLE MUSCARINIC RECEPTOR SUBTYPES MEDIATING PULMONARY-EDEMA 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 (M(1)-selective antagonist) and 4-DAMP (M(3)-selective antagonist) altered. this response, producing a dose-dependent shift to the right of the ACh concentration-Kf,c response curve. By contrast, the M(2)-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. M(1) and M(3) receptors seem to stimulate the release of neuropeptides from C-fibres, whereas M(2) receptors have an inhibitory effect on these fibres.