Sensitization alters contractile responses and calcium influx in human airway smooth muscle.
Although an abnormality in airway smooth muscle has been promoted as a mechanism for airway hyperresponsiveness, there is, so far, little evidence to support this. We investigated whether in vitro hyperresponsiveness to pharmacologic agents could be induced in human airway tissue by passive sensitization and whether these changes in contractile responses were related to an alteration in calcium mobilization. Human bronchial tissue was incubated in serum with a high RAST titer to Dermatophagoides farinae. Control tissues were incubated in serum taken from a skin test-negative donor with a total IgE of less than 10 IU/ml. We compared contractile responses to histamine, KCI, and carbachol in nonsensitized and sensitized tissues and examined the effect on these responses of the calcium voltage-dependent channel agonist, BAY K8644 (10(-6) mol/L). We found that sensitization significantly increased responses to histamine, depressed responses to carbachol, and increased the involvement of the calcium voltage-dependent channel in contractions to KCl. These results suggest that airway hyperresponsiveness may be associated with altered calcium mobilization in airway smooth muscle.
Black
J L
JL
Department of Pharmacology, University of Sydney, N.S.W., Australia.
Marthan
R
R
Armour
C L
CL
Johnson
P R
PR
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000368:Aged; D001980:Bronchi / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D005260:Female; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007114:Immunization; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology
D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D006632:Histamine; D002217:Carbachol; D002118:Calcium