Decreased sensitivity and response of isolated tracheal muscle to methacholine and histamine without changing the activity of pulmonary muscarinic receptors in the egg albumin-sensitized guinea pig.

Guinea pigs were sensitized by daily intraperitoneal injections of 100 mg of egg albumin for 3 consecutive days and sacrificed at 30-35 days after the last injection. The in vitro sensitivity and response of the sensitized tracheal muscle to methacholine and histamine were significantly less than those of littermate controls. However, there was no difference between the dissociation constants and concentrations of pulmonary muscarinic receptor binding sites of the control and sensitized guinea pigs. We conclude that subsensitivity and hyporesponsiveness to methacholine and histamine occur in the airway muscle of this guinea pig model of experimental asthma and suggest that the decreased reactivity to methacholine might be due to defects beyond the receptor.