prostaglandin-d2 and enprofylline

Prostaglandins (PGs) F2 alpha and D2 are bronchoconstrictor agents which are released under allergic conditions such as asthma. The efficacy and potency of PGF2 alpha and PGD2 differ in some tissues. We compared the effects of these two PGs in sensitized human parenchymal strips. In six experiments, PGF2 alpha 0.1 and 0.3 microM produced greater contractions than PGD2 at the same concentrations. There were no significant differences between the contractions from the two PGs at concentrations of 0.01, 0.03, 1.0-10 microM and the two PGs appeared to be equipotent. We studied the effects of the anti-asthmatic drug theophylline, and its analogue enprofylline, on the contraction caused by these PGs. Theophylline 100 microM caused no change to the cumulative concentration response curves. However, enprofylline 100 microM reduced the PGF2 alpha-induced contractions.

Topics: Bronchodilator Agents; Dinoprost; Histamine; Humans; Lung; Muscle Contraction; Muscle, Smooth; Prostaglandin D2; Theophylline; Xanthines

Human lung bronchiolar segments (about 2 mm long and with a diameter of 0.6-1.5 mm) were dissected and circular muscle tension recorded. Airways were identified by histology and in some preparations by relaxant responses to noradrenaline (0.1-10 microM). Adenosine (1-100 microM) produced only very weak contractions, whereas carbachol (EC50 = 0.40 microM), histamine (EC50 = 0.63 microM), prostaglandin D2 (EC50 = 0.50 microM), substance P (EC50 = 4.6 microM) and ATP (1-100 microM) produced much greater ones. The contractions generally developed rapidly and were stable. The mean maximum increase in tension achieved with the most efficient constrictor, carbachol, was 0.5 g. ATP was the least efficient producing only about 40% of carbachol's maximum. Terbutaline, theophylline and enprofylline relaxed carbachol (2.0 microM = EC70)-contracted preparations. Terbutaline (3-3000 nM) relaxed 4 out of 11 bronchioles. Theophylline (10-4000 microM) and enprofylline (1-400 microM) consistently relaxed the bronchiolar preparations including those exhibiting little responsiveness to the beta 2-adrenoceptor agonist. Since enprofylline (which does not block adenosine receptors) was a five times more potent relaxant than theophylline and since adenosine produced only weak contractions, antagonism of adenosine receptors is probably not involved in relaxation of the small airways. It is suggested that the present data, which apparently differ from those obtained with lung parenchymal strips, are of relevance for human small airways responsiveness.

Topics: Adenosine; Adenosine Triphosphate; Bronchi; Bronchodilator Agents; Carbachol; Histamine; Humans; In Vitro Techniques; Lung; Muscle Contraction; Muscle Relaxation; Muscle, Smooth; Prostaglandin D2; Prostaglandins D; Substance P; Terbutaline; Theophylline; Xanthines