title: A role for inflammatory mediators in airway hyper-responsiveness.
abstract: We have demonstrated that PGF2 alpha potentiates airway contraction in vitro and suggested that this response may be mediated by TxA2. We have localized the site of action of PGF2 alpha to a point distal to the parasympathetic ganglion and shown that it is a specific effect since PGD2 produces no similar potentiation. The mechanism of the potentiation may be by a direct alteration in smooth muscle sensitivity induced by TxA2 (Fig. 4). In our previous studies we have been able to induce hyperresponsiveness in vivo (Berend et al., 1986) but no increased responsiveness in vitro (Armour et al., 1987b). In vivo airway hyperresponsiveness may depend on the presence of a mediator like TxA2 which has a short half-life, is produced by continual stimulation of inflammatory cells and which is "washed out" in vitro once the source of stimulation is removed. The fact that we can demonstrate an increase in sensitivity in vitro using PGF2 alpha or a TxA2 analogue, combined with the fact that both mediators are released from a variety of inflammatory cells suggests that one or both of these agents may mediate part of the increased responsiveness observed in asthma.
authors.affiliation: Department of Pharmacology, University of Sydney, N.S.W., Australia.
authors.forename: C L
authors.initials: CL
authors.lastname: Armour
authors.forename: J L
authors.initials: JL
authors.lastname: Black
authors.forename: P R
authors.initials: PR
authors.lastname: Johnson
mesh_terms: D000818:Animals; D001249:Asthma / Q000209:etiology*; D001980:Bronchi / Q000294:innervation; D001986:Bronchial Spasm / Q000209:etiology*; D002217:Carbachol; D015237:Dinoprost; D006632:Histamine; D009130:Muscle, Smooth / Q000187:drug effects* / Q000503:physiopathology; D011460:Prostaglandins F / Q000502:physiology*; D011817:Rabbits; D013928:Thromboxane A2 / Q000502:physiology*; D014132:Trachea / Q000294:innervation
chemical_list: D011460:Prostaglandins F; D013928:Thromboxane A2; D006632:Histamine; D002217:Carbachol; D015237:Dinoprost