Muscarinic hyperresponsiveness of antigen-sensitized feline airway smooth muscle in vitro

R. W. Mitchell From the Asthma, Allergy and Immunology Disease Research Center, Section of Pulmonary and Critical Care Medicine, Department of Medicine, Physiologic and Pharmacologic Sciences, and the Committees on Comparative Medicine and Pathology, Immunology, and Cell Physiology and Clinical Pharmacology, Division of the Biological Sciences, The University of Chicago, Chicago, IL 60637.

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I. M. Ndukwu From the Asthma, Allergy and Immunology Disease Research Center, Section of Pulmonary and Critical Care Medicine, Department of Medicine, Physiologic and Pharmacologic Sciences, and the Committees on Comparative Medicine and Pathology, Immunology, and Cell Physiology and Clinical Pharmacology, Division of the Biological Sciences, The University of Chicago, Chicago, IL 60637.

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A. R. Leff From the Asthma, Allergy and Immunology Disease Research Center, Section of Pulmonary and Critical Care Medicine, Department of Medicine, Physiologic and Pharmacologic Sciences, and the Committees on Comparative Medicine and Pathology, Immunology, and Cell Physiology and Clinical Pharmacology, Division of the Biological Sciences, The University of Chicago, Chicago, IL 60637.

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P. A. Padrid From the Asthma, Allergy and Immunology Disease Research Center, Section of Pulmonary and Critical Care Medicine, Department of Medicine, Physiologic and Pharmacologic Sciences, and the Committees on Comparative Medicine and Pathology, Immunology, and Cell Physiology and Clinical Pharmacology, Division of the Biological Sciences, The University of Chicago, Chicago, IL 60637.

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Abstract

Objective

To determine the effect of in vivo antigen sensitization (Ascaris suum) of cats on tracheal smooth muscle (TSM) and bronchial smooth muscle (BSM) muscarinic reactivity in vitro.

Animals

Healthy domestic shorthair cats of either sex.

Procedure

Cats were sensitized and were longterm antigen (or sham) challenge exposed for 6 weeks by aerosolization with soluble Ascaris suum. Tracheal and BSM preparations were obtained and stimulated in vitro by electrical field stimulation (EFS), acetylcholine (ACh, a muscarinic agonist), and physostigmine (an AChase inhibitor). Responses were compared with responses of comparable tissues from sham antigen challenge-exposed cats.

Results

Tracheal and BSM from sensitized, compared with sham-sensitized (control), cats had greater isometric contraction (expressed as percentage of the response observed for isotonic, 63 mM KCl-elicited contraction [% KCI]) in response to endogenous (EFS) and exogenous muscarinic receptor activation (ACh). Contractions in response to EFS by TSM from control cats were 74 % KCI vs 97 %KCI for antigen-sensitized TSM (P < 0.04). Muscarinic responses were augmented comparably by in vivo sensitization; TSM from control cats contracted to 190 % KCI vs 230 % KCl (P < 0.03) for TSM from immune-sensitized cats. Physostigmine augmented responses of all tissues to ACh so that TSM from control (290 %KCI) and antigen-sensitized (257 %KCI) cats were similar. Responses of BSM from antigen-sensitized cats had similar augmentation of contractile response to EFS and ACh.

Conclusions

Long-term in vivo antigen sensitization increases numbers of muscarinic receptors on airway smooth muscle or decreases the availability or activity of AChase in cats.

Clinical Relevance

Modulation of muscarinic receptors may be useful for treatment of asthmatic cats with in vivo airway hyperreactivity. (Am J Vet Res 1997;58:672–676)

Abstract

Objective

To determine the effect of in vivo antigen sensitization (Ascaris suum) of cats on tracheal smooth muscle (TSM) and bronchial smooth muscle (BSM) muscarinic reactivity in vitro.

Animals

Healthy domestic shorthair cats of either sex.

Procedure

Cats were sensitized and were longterm antigen (or sham) challenge exposed for 6 weeks by aerosolization with soluble Ascaris suum. Tracheal and BSM preparations were obtained and stimulated in vitro by electrical field stimulation (EFS), acetylcholine (ACh, a muscarinic agonist), and physostigmine (an AChase inhibitor). Responses were compared with responses of comparable tissues from sham antigen challenge-exposed cats.

Results

Tracheal and BSM from sensitized, compared with sham-sensitized (control), cats had greater isometric contraction (expressed as percentage of the response observed for isotonic, 63 mM KCl-elicited contraction [% KCI]) in response to endogenous (EFS) and exogenous muscarinic receptor activation (ACh). Contractions in response to EFS by TSM from control cats were 74 % KCI vs 97 %KCI for antigen-sensitized TSM (P < 0.04). Muscarinic responses were augmented comparably by in vivo sensitization; TSM from control cats contracted to 190 % KCI vs 230 % KCl (P < 0.03) for TSM from immune-sensitized cats. Physostigmine augmented responses of all tissues to ACh so that TSM from control (290 %KCI) and antigen-sensitized (257 %KCI) cats were similar. Responses of BSM from antigen-sensitized cats had similar augmentation of contractile response to EFS and ACh.

Conclusions

Long-term in vivo antigen sensitization increases numbers of muscarinic receptors on airway smooth muscle or decreases the availability or activity of AChase in cats.

Clinical Relevance

Modulation of muscarinic receptors may be useful for treatment of asthmatic cats with in vivo airway hyperreactivity. (Am J Vet Res 1997;58:672–676)

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