The effects of intraluminal and extraluminal drug application on secretion and smooth muscle tone in the ferret liquid-filled trachea in vitro.

With the ferret liquid-filled trachea in vitro, intraluminal methacholine (MCh), phenylephrine (PE) and histamine (Hist) increased smooth muscle tone and salbutamol (Salb) decreased tone. Lysozyme output was increased by intraluminal MCh and PE. Albumin transport into the lumen was not altered by intraluminal Hist, Salb or PE. The concentration-response curves for smooth muscle contraction and for lysozyme output to extraluminal MCh lay to the left of those for intraluminal MCh. Indomethacin shifted the smooth-muscle response curves to MCh significantly to the left but did not significantly alter lysozyme output. Extraluminal MCh produced a concentration-dependent increase in albumin output whilst intraluminal MCh did so in one of three studies. Albumin output in response to MCh was not significantly altered by indomethacin. Thus, MCh has a less potent effect on smooth muscle and lysozyme secretion and, to a lesser extent, on epithelial albumin transport when given intraluminally. This may be because the epithelium restricts diffusion of the drug or due to the production of a non-prostanoid factor which inhibits smooth muscle responsiveness. Smooth muscle responsiveness is enhanced by blocking cyclooxygenase activity, suggesting MCh-induced release of a prostanoid with relaxant activity.