Relaxation by calcium antagonists of potassium-contracted trachea from normal and sensitized guinea-pigs: influence of epithelium and the surface of drug entry.
A technique by which drug access was restricted to either the mucosal or the adventitial surface of tracheal rings, isolated from normal (unsensitized) or sensitized guinea-pigs, was used to study the role of the epithelium in the relaxation produced by calcium antagonists (verapamil, nifedipine, cinnarizine and flunarizine) of K(+)-induced contraction. In trachea from normal guinea-pigs, the relaxation to verapamil for unrestricted or mucosal drug entry was reduced in the absence of epithelium, whereas the relaxation produced by nifedipine, cinnarizine or flunarizine was unchanged. In sensitized trachea, the relaxation elicited by the calcium antagonists tested was similar in intact and epithelium-denuded tracheal rings irrespective of the surface of drug entry. These results confirm that the epithelium influences the relaxation to verapamil. This modulatory effect is absent in sensitized trachea and is not shared by other calcium antagonists.
Román
M
M
Departamento de Fisiología y Farmacología, Universidad de Alcalá, Madrid, Spain.
Pascual
R
R
Iriarte
C F
CF
Villanueva
M M
MM
Ortiz
J L
JL
Cortijo
J
J
Morcillo
E
E
D000818:Animals; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D002936:Cinnarizine / Q000494:pharmacology; D004848:Epithelium / Q000502:physiology; D005620:Freund's Adjuvant / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D011188:Potassium / Q000494:pharmacology*; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000503:physiopathology; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013499:Surface Properties; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D002121:Calcium Channel Blockers; D012710:Serum Albumin, Bovine; D002936:Cinnarizine; D005620:Freund's Adjuvant; D011188:Potassium