The symptoms of allergic asthmatic patients typically worsen during the night, especially during the early morning hours. Although 24-hour variations in the environment contribute to the intensification of the asthmatic condition nocturnally, environmental changes themselves do not fully explain the temporal aspects of this disease. Orcadian (about 24-hour) rhythms in critical bioprocesses constitute significant contributory factors. The exacerbation of asthma during the night represents the changing status of biological functioning due to circadian rhythms in bronchial patency; airways hyperreactivity to acetylcholine, histamine, and house dust; and plasma cortisol, epinephrine, histamine, and cyclic AMP, among others.
Overview of PAF biosynthesis and catabolism Cellular origins of PAF PAF receptors PAF receptor antagonists PAF and cell activation PAF and cardiovascular disease PAF and lung disease PAF and renal disease PAF and the gastrointestinal tract Effects of PAF on blood elements PAF and the skin PAF and the nervous system PAF and the immune system PAF and the establishment of pregnancy PAF and fetal development.
Bradykinin (BK) has several effects on airway function which may be relevant in obstructive airways disease. These effects are mediated via B2-receptors. BK is a potent bronchoconstrictor in animals and humans in vivo. Bradykinin contracts airway smooth muscle, is a potent bronchial vasodilator, increases microvascular leakage, stimulates epithelial cells to release bronchodilators and stimulates mucus secretion. Perhaps its most important action is the activation of sensory nerves in airways, leading to reflex bronchoconstriction, coughing and neurogenic inflammation through the release of neuropeptides from sensory nerves.
We have demonstrated recently that exogenous prostaglandin E 2 (PGE 2 ) inhibits electrical field stimulation (EFS)‐induced acetylcholine (ACh) release from parasympathetic nerve terminals innervating guinea‐pig trachea. In the present study, we have attempted to characterize the pre‐junctional prostanoid receptor(s) responsible for the inhibitory action of PGE 2 and to assess whether other prostanoids modulate, at a prejunctional level, cholinergic neurotransmission in guinea‐pig trachea. To this end, we have investigated the effect of a range of both natural and synthetic prostanoid agonists and antagonists on EFS‐evoked [ 3 H]‐ACh release. In epithelium‐denuded tracheal strips pretreated with indomethacin (10 μ M ), PGE 2 (0.1 n M –1 μ M ) inhibited EFS‐evoked [ 3 H]‐ACh release in a concentration‐dependent manner with an EC 50 and maximal effect of 7.62 n M and 74% inhibition, respectively. Cicaprost, an IP‐receptor agonist, PGF 2α and the stable thromboxane mimetic, U46619 (each at 1 μ M ), also inhibited [ 3 H]‐ACh release by 48%, 41% and 35%, respectively. PGD 2 (1 μ M ) had no significant effect on [ 3 H]‐ACh release. The selective TP‐receptor antagonist, ICI 192,605 (0.1 μ M ), completely reversed the inhibition of cholinergic neurotransmission induced by U‐46619, but had no significant effect on similar responses effected by PGE 2 and PGF 2α . A number of EP‐receptor agonists mimicked the ability of PGE 2 to inhibit [ 3 H]‐ACh release with a rank order of potency: GR63799X (EP 3 ‐selective)>PGE 2 >M&B 28,767 (EP 3 selective)>17‐phenyl‐ω‐trinor PGE 2 (EP 1 ‐selective). The EP 2 ‐selective agonist, AH 13205 (1 μ M ), did not affect EFS‐induced [ 3 H]‐ACh release. AH6809 (10 μ M ), at a concentration 10 to 100 times greater than its pA 2 at DP‐, EP 1 ‐ and EP 2 ‐receptors, failed to reverse the inhibitory effect of PGE 2 or 17‐phenyl‐ω‐trinor PGE 2 on [ 3 H]‐ACh release. These results suggest that PGE 2 inhibits [ 3 H]‐ACh release from parasympathetic nerves supplying guinea‐pig trachea via an interaction with prejunctional prostanoid receptors of the EP 3 ‐receptor subtype. Evidence for inhibitory prejunctional TP‐ and, possibly, IP‐receptors was also obtained although these receptors may play only a minor role in suppressing [ 3 H]‐ACh release when compared to receptors of the EP 3 ‐subtype. However, the relative importance of the different receptors will depend not only on the sensitivity of guinea‐pig trachea to prostanoids but on the nature of the endogenous ligands released locally that have activity on parasympathetic nerves. British Journal of Pharmacology (1998) 123 , 1246–1252; doi: 10.1038/sj.bjp.0701720
The measurement of exhaled nitric oxide (NO) made its way as a new lung function from basic discovery to clinical application in less than a decade. As was the case with spirometry, after the initial bloom of the field, making and following basic discoveries, contradictory findings and unexpected discoveries brought the area to a halt, and scientists have been prompted to take a fresh look at all of the available data and the future horizon.
No abstract is provided for this article.
Alveolar macrophages play a critical role in innate and acquired immunity, in the defense of the respiratory tract against pathogens, and in the clearance of inhaled particles. They also play an important role in the inflammatory response and there is increasing evidence that they play a pivotal role in the pathophysiology of COPD. Because of the extraordinary diversity of macrophage responses they can account for most of the known features of COPD (1-5) (Fig. 1).
