Responsiveness to histamine in human sensitized airway smooth muscle.
Passive sensitization of human isolated airway smooth muscle increases contractile responses to histamine. We looked to see whether this increase was due to an alteration in the relative role of histamine H1 and H2 receptors. Human bronchial spiral strips obtained at thoracotomy were passively sensitized by incubation in serum from atopic asthmatic patients to Dermatophagoïdes pteronyssinus and control strips were incubated in serum from healthy non-allergic non-atopic subjects. We also studied spiral strips dissected from two spontaneously sensitized human lung specimens. Cumulative concentration-response curves (CCRC) to Ca2+ (10(-5) -3 x 10(-2) M) were constructed either in the presence of 10(-5) M histamine alone or in that of the combination histamine and the H2 antagonist cimetidine (10(-5) M). Unlike in the absence of histamine, Ca2+ CCRC in the presence of histamine alone were significantly shifted to the left in the passively sensitized tissues (mean EC50: 5.7 x 10(-4) M) compared to control ones (mean EC50: 9.3 x 10(-4) M, n = 6, P < 0.05). Addition of cimetidine to histamine did not alter the Ca2+ CCRC either in the control or in passively or spontaneously sensitized airway smooth muscle. These results suggest that (i) passive sensitization increases contractile response to Ca2+ of human bronchial smooth muscle in the presence of histamine; (ii) this increase is not due to a difference in the H1- vs H2-mediated response; and (iii) H2-mediated effects do not play a significant role in spontaneously sensitized human lung as both in the non-sensitized and passively sensitized lung.
Marthan
R
R
Laboratoire de Physiologie, Faculté de Médecine Victor Pachon, Université de Bordeaux II, France.
Crevel
H
H
Guénard
H
H
Savineau
J P
JP
D000368:Aged; D000704:Analysis of Variance; D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D006967:Hypersensitivity / Q000503:physiopathology; D007116:Immunization, Passive; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D008925:Mites / Q000276:immunology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011968:Receptors, Histamine / Q000502:physiology*
D011968:Receptors, Histamine; D002927:Cimetidine; D006632:Histamine; D002118:Calcium