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Role of epithelium in agonist‐induced contractile responses of guinea‐pig trachealis: influence of the surface through which drug enters the tissue
Author(s) -
Iriarte C.F.,
Pascual R.,
Villanueva M.M.,
Román M.,
Cortijo J.,
Morcillo E.J.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb12697.x
Subject(s) - trachealis muscle , histamine , acetylcholine , epithelium , guinea pig , drug , respiratory epithelium , chemistry , anatomy , pharmacology , endocrinology , medicine , biology , pathology
1 A method has been used in guinea‐pig isolated tracheal rings to achieve selective drug entry from the adventitial or mucosal surface. A study has been made of the effects of epithelium removal on responses to spasmogens entering the tissue solely from the adventitial or the mucosal surface. 2 Cumulative concentration‐response curves for KCl (1 to 100 m m ), acetylcholine (0.1 μ m to 10 m m ) and histamine (1 μ m to 1 m m ) were constructed in intact and epithelium‐denuded tracheal rings in circumstances where drug entry was unrestricted or restricted to the adventitial or mucosal surface. 3 Epithelium removal did not alter the responsiveness or sensitivity of tracheal rings to KCl either when drug entry was unrestricted or when drug entry was restricted to the adventitial or mucosal surface. 4 When acetylcholine entered from the mucosal or adventitial surfaces of intact tracheal rings its concentration‐response curve was displaced to the right with respect to that obtained for unrestricted drug entry. A greater rightward shift was observed for mucosal drug entry than for adventitial drug entry. Epithelium removal potentiated acetylcholine entering from the mucosal surface to a greater extent (27.5 fold) than it potentiated acetylcholine entering from both surfaces (4 fold). Epithelium removal did not potentiate effects of acetylcholine entering from the adventitial surface alone. 5 In intact tracheal segments, concentration‐response curves for histamine entering from the mucosal surface were displaced to the right compared with those for histamine entering in an unrestricted fashion or from the adventitial surface alone. This displacement was absent in epithelium‐denuded preparations. Epithelium removal potentiated (2–3 fold) histamine entering from the mucosal surface or entering in an unrestricted way. It did not potentiate histamine entering from the adventitial surface alone. 6 Our findings suggest that the epithelium does not modulate tracheal responses to KCl. Its ability to modulate responses to acetylcholine and histamine is observed when these spasmogens enter the tissue from the mucosal surface but not when they enter from the adventitial surface. The mechanism by which epithelium removal preferentially potentiates acetylcholine and histamine entering from the mucosal rather than the adventitial surface remains to be determined.