Prostaglandin E2, but not prostacyclin inhibits histamine-induced contraction of human bronchial smooth muscle.
The effects of exogenous prostaglandin E2 and prostacyclin on the function of epithelium-intact and epithelium-denuded human bronchial smooth muscle and the role of these mediators in the inhibition of histamine-induced contraction was examined using bronchi obtained from 22 patients undergoing thoracotomy. Under resting tension, a variable biphasic contraction-relaxation or monophasic relaxation was observed following the cumulative addition of exogenous prostaglandin E2 or prostacyclin. Cumulative addition of these mediators to pre-contracted bronchi produced incomplete relaxation, irrespective of the presence of epithelium. Addition of prostaglandin E2, at a concentration equating to that produced after histamine stimulation (1.2 x 10(-9)M), produced a reduction (24%) in the maximum contractile response (Emax) to a subsequent histamine challenge (P < 0.03). However, a similar response was not observed after the addition of prostacyclin at a concentration similar to that produced endogenously (6.5 x 10(-10)M). The combined addition of both mediators resulted in a significant reduction (26%) in the Emax to histamine (P < 0.02) but this effect was not statistically different to that of prostaglandin E2 alone. The addition of supramaximal concentrations (1 microM) of each prostanoid, either alone or in combination, did not inhibit responses to histamine. These data suggest that whilst prostaglandin E2 does not act as a direct acting relaxant agonist, it may inhibit histamine-induced muscle contraction and thereby contribute to the observed tachyphylaxis to this mediator. In contrast, prostacyclin appears to be of little importance in modulating human bronchial smooth muscle responses to histamine either directly or by enhancing responses to prostaglandin E2. The inhibitory effect of prostaglandin E2 appears to be concentration-dependent and suggests a bimodal action of this mediator in human airways.
Knight
D A
DA
Asthma and Allergy Research Unit, University Department of Medicine, Queen Elizabeth II Medical Centre, Nedlands, Australia.
Stewart
G A
GA
Thompson
P J
PJ
D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D011464:Epoprostenol / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D013618:Tachyphylaxis
D006632:Histamine; D011464:Epoprostenol; D015232:Dinoprostone