Histamine-induced contraction of human isolated bronchus is enhanced by endogenous prostaglandin F2 alpha and activation of TP receptors.
The effect of histamine on the production of prostaglandin F2 alpha and the actions of prostaglandin F2 alpha on the responsiveness of human isolated bronchial smooth muscle were examined by organ bath techniques using bronchi from lung tissue resected from 18 patients. Following exposure to histamine, epithelium-intact bronchi generated 34.26 +/- 16.3 pg of prostaglandin F2 alpha/mg of tissue and epithelium-denuded preparations produced 32.62 +/- 11.83 pg/mg, suggesting that histamine-induced release of prostaglandin F2 alpha was from non-epithelial sources, presumably smooth muscle. The histamine H2 receptor antagonist ranitidine did not affect the release of prostaglandin F2 alpha, suggesting that its generation may have resulted from histamine H1 receptor activation. Carbachol did not influence prostaglandin F2 alpha generation. Contractile responses to histamine, prostaglandin F2 alpha and carbachol were measured in the presence and absence of the prostaglandin TP receptor antagonist SQ 29,548 ([1 S-[1 alpha,2 beta(5Z),3 beta,4 alpha]]-7-[3[[2-[9-phenylamino)carbonyl]hydrazino] methyl-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid) (0.4 microM). SQ 29,548 abolished responses to prostaglandin F2 alpha suggesting that contractions were mediated via TP receptors. Exposure to SQ 29,548 also produced a 3-fold rightward shift in the concentration-effect curve for histamine (P = 0.01) without influencing the maximum response. SQ 29,548 did not affect responses to carbachol. These results suggest that histamine selectively stimulates the generation of prostaglandin F2 alpha from epithelium-denuded human airway tissue (presumably from the smooth muscle), which in turn, amplifies the contractile responses of human airway smooth muscle to histamine.
Knight
D A
DA
Department of Medicine, University of Western Australia, Nedlands, Australia. dknight@prl.pulmonary.ubc.ca
Stewart
G A
GA
Thompson
P J
PJ
D019086:Bridged Bicyclo Compounds, Heterocyclic; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D015237:Dinoprost / Q000378:metabolism / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000187:drug effects*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D018679:Cholinergic Agonists; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011982:Receptors, Prostaglandin; D006632:Histamine; C045749:SQ 29548; D002217:Carbachol; D015237:Dinoprost