Epithelial modulation of tracheal smooth muscle response to antigenic stimulation

Abstract

The role of the epithelium has been studied in the contractile responses of rat trachea. The different modulations observed are discussed in respect to vagal components of the epithelial layer. Responses of rat trachea to immunologic stimulation are shown to be dependent on the presence of the epithelium, which prolongs the relaxation stage without affecting the contractions. This prolongation is abolished by neonatal capsaicin pretreatment, whereas substance P induces a significantly greater relaxation of serotonin-precontracted intact than deepithelialized trachea. Serotonin concentration-response curves are shifted to the right in intact preparations, which is partly reversed by neonatal capsaicin pretreatment, but a hyporeactivity of the tissue exists. A relaxing factor released by the epithelium is hypothesized, possibly dependent on substance P-ergic innervation. Muscarinic cholinergic innervation slightly modulates the contractions but not the relaxations in antigen-induced responses, independently on the presence of the epithelial layer. 4-Aminopyridine induces epithelium-dependent potentiations of contractions to antigen and to serotonin, which involves acetylcholine at one step of the reaction cascade. Epithelial-dependent contracting and relaxing factors are thus suggested in rat trachea.

The epithelium and the pharmacology of guinea‐pig tracheal tone in vitro

“…Ovalbumin in sensitized guinea-pig tracheae became mqre potent after epithelium removal, whereas its maximum effect was either unchanged (Hay et al, 1986a) or increased (Hay et al, 1987). In sensitized rat tracheae Frossard & Muller (1986) found a diminished response to ovalbumin when the epithelium had been removed. Tschirhart & Landry (1986) found that epithelium removal in guinea-pig tracheal preparations increased the potency of substance P by over forty times.…”

“…In preparations treated with thiorphan to prevent its breakdown, substance P was slightly more potent in the absence of epithelium. It may also be noted that Frossard & Muller (1986) found that substance P relaxed rat tracheal preparations and this response was slightly reduced by epithelium removal.…”

“…It has had an impact on work with isolated airway preparations where the focus has been on a role for the epithelium in regulation of airway smooth muscle tone. Despite the fact that many of the accumulated observations are negative or contradictory, it has generally been maintained that airway epithelium importantly affects tracheobronchial smooth muscle reactivity (Barnes et al, 1985;Flavahan et al, 1985;Farmer et al, 1986;Finnen et al, 1986;Frossard & Muller, 1986;Goldie et al, 1986;Hay et al, 1986a,b;Holroyde, 1986;Reaburn et al, 1986a,b;Thompson et al, 1986;Tschirhart & Landry, 1986;Nijkamp & Folkerts, 1987). It is understandable that positive results have been searched for and related to the pathology and pharmacology of asthma.…”

Comparison of the effects of epithelium removal and of an enkephalinase inhibitor on the neurokinin‐induced contractions of guinea‐pig isolated trachea

“…In support of the latter suggestion, Frossard & Muller (1986) and Tschirhart & Landry (1986) have shown that a relaxant factor (EpDRF) might be released from airway epithelium during the action of substance P on rat or guinea-pig trachea.…”

“…The mechanical removal of the epithelial layer hydroxytryptamine (5-HT) and substance P and to increases the sensitivity of the isolated trachea of antigenic challenge (Barnes et al, 1985;Flavahan et several species to a variety of bronchoconstrictor Goldie et al, 1986;Frossard & Muller, agents, such as histamine, acetylcholine, 5-1986;Hay et al, 1986a, b;Holroyde, 1986;Raeburn et al, 1986;Tschirhart & Landry, 1986;Tschirhart 1 Author for correspondence at: Laboratoire de Pharma-factor which modulates airway smooth muscle tone (Barnes et al, 1985;Flavahan et al, 1985;Frossard & Muller, 1986;Raeburn et al, 1986, Tschirhart & Landry, 1986Ilhan & Sahin, 1986;Tschirhart et al, 1987;Hay et al, 1987;Butler et al, 1987). In support of the latter suggestion, Frossard & Muller (1986) and Tschirhart & Landry (1986) have shown that a relaxant factor (EpDRF) might be released from airway epithelium during the action of substance P on rat or guinea-pig trachea.…”