Increased Muscarinic Receptor Blockade by Atropine in Tracheal Chains of Ovalbumin-Sensitized Guinea Pigs

Abstract

Drug delivery to the receptor sites and receptor affinity could be determinant factors for increased bronchial responsiveness seen in asthma. Competitive antagonism blockade which is measured as dose ratio – 1 (DR-1) depends only on these two factors. Therefore, in this study we examined the muscarinic receptor blockade by atropine on isolated tracheal chains of sensitized compared to control guinea pigs. An experimental model of asthma was induced in guinea pigs by sensitization of animals with injection and inhalation of ovalbumin (OA). The responses of tracheal chains of sensitized and control animals (for each group n = 10) to cumulative concentrations of methacholine in the absence and presence of 5 nmol/l atropine were measured, and the effective concentrations of methacholine causing 50% of maximum response (EC₅₀ M) were obtained. The atropine blockade (DR-1) was calculated by: (post-atropine EC₅₀ M/EC₅₀ M) – 1. The responses of tracheal chains to 0.1% OA, relative to contraction obtained by 10 mmol/l methacholine, were also measured. The tracheal responses of sensitized guinea pigs were significantly higher than those of control animals to both OA (mean ± SEM, 55.94 ± 5.22 vs. 2.59 ± 0.85%, p < 0.001) and methacholine (EC₅₀ M for asthmatic and control animals were 0.88 ± 0.27 and 2.00 ± 0.26 μmol, respectively, p < 0.01). The muscarinic receptor blockade by atropine (DR-1) was also significantly higher in tracheas of asthmatic compared to that of control animals (131.12 ± 19.82 vs. 24.50 ± 3.19, p < 0.001). There were significant correlations between tracheal response to OA and EC₅₀ M (r = –0.644, p = 0.002) and also between DR-1 and tracheal responses to both OA (r = 0.738, p < 0.001) and EC₅₀ M (r = –0.679, p < 0.001). This enhanced muscarinic receptor blockade in tracheal chains of sensitized animals confirms our previous findings which was predicted to be due to the increased drug delivery to the receptors. Drug delivery could also be a determinant factor for bronchial responsiveness to stimuli in asthma.

Increased Tracheal Responsiveness to Beta-Adrenergic Agonist and Antagonist in Ovalbumin-Sensitized Guinea Pigs

“…The consistent antagonism blockade of the present in vitro study and our previous in vitro [12,17] and in vivo [3,15,16] studies indicated that in asthma either receptor affinity (Ka) or drug delivery to the receptors ([I]) or both of these factors are increased. We suggest that airway hyperreponsiveness to stimuli including isoprenaline and enhanced antagonism blockade may be caused by epithelial damage which is a well-recognized feature in asthma [23].…”

“…The results of ß-adrenergic receptor blockade (CR -1) by propranolol in the sensitized compared to the control group seen in this study was also very similar to those of ß-adrenergic, muscarinic, and histamine (H 1 ) receptor blockades in our previous in vivo findings with propranolol [3], atropine [15], and chlorpheniramine [16] in asthmatic compared to normal subjects and in vitro results with atropine [12] and chlorpheniramine [17] in sensitized compared to the control guinea pigs.…”

“…In each experiment a cumulative log concentration-response curve of methacholine-induced contraction of the tracheal chain was also obtained as previously described [12].…”

The effects of Valeriana officinalis L. hydro-alcoholic extract on depression like behavior in ovalbumin sensitized rats

“…[12] This model is accompanied with acute inflammatory events including infiltration of inflammatory cells such as eosinophils, mast cells, neutrophils and lymphocytes. [1314] In sensitized animals, both CD4+ and CD8+ cells are activated which they then express Th2 cytokines.…”

Beta-1 selective adrenergic antagonist landiolol and esmolol can be safely used in patients with airway hyperreactivity

“…An experimental model of asthma was established by using the white-of-egg albumin ovalbumin (Ova) as an antigen. [19][20][21] Briefly, the asthmatic group received Ova (1 mg/2 mL saline) intraperitoneally, and after 2 weeks the Ova sensitization was boosted by exposure to aerosolized Ova (10 mg, 1 mL saline) for 10 minutes. The control group received the same volume of sterilized .9% saline instead of Ova.…”