CHANGES OF MUSCARINIC RECEPTORS IN NASAL MUCOSA IN GUINEA PIGS SENSITIZED WITH OVALBUMIN AND EFFECT OF ANTI-ALLERGIC DRUGS TO THESE RECEPTORS

Abstract

Our previous study showed that the increased density of cholinergic muscarinic receptors (muscarinic receptors) in the nasal mucosa of subjects with nasal allergy is induced secondarily by some pathophysiological changes in the nasal mucosa which is related intimately with the development of hyperreactive nasal symptoms.The present study was designed to elucidate the mechanism of an increase in the density of muscarinic receptors. Guinea pigs were sensitized intraperitoneally using 20μg ovalbumin and 10mg of aluminum hydroxide in 1 ml of normal saline 7 times every 2 weeks. After that, transairway sensitizations was performed by ultranebulization of 3ml of 0.01% ovalbumin in normal saline consecutively for 5 days. One week later, nasal provocation was performed daily for 7 days by nasal instillation of 50μl of 1% ovalbumin in normal saline, which caused typical hyperreactive nasal symptomes in most guinea pigs. Then the effect of anti-allergic drugs to cholinergic receptors was studied.After provocation, DSCG (4mg/body) or flunisolide (50μg/body) was administered by nasal instillation. And azelastine (2mg/body), clemastine (2mg/body) or tranilast (300mg/body) was given orally daily for 4 weeks. During administration of drugs, nasal provocations were continued 3 times for a week.The increased density of muscarinic receptors was reproduced in the nasal membrane of guinea pigs which was provocated repeatedly with antigen after trans-airway sensitization. On the other hand, no significant change was observed in the nasal membrase of guinea pigs sensitized with ovalbumin without nasal provocation. All of anti-allergic drugs studied suppressed an increase in the density of muscarinic receptors. However, no significant change was observed in the density of muscarinic receptors when azelatine or cremastine was administered to normal guinea pigs. There were no significant changes in the affinity of muscarinic receptors in the nasal mucosa between corresponding groups.Above results indicate that an increase in the density of muscarinic receptors observed in the nasal mucosa of subjects with nasal allergy has been induced secondarily by some of chemical mediators which have been released by antigen antibody reactions. Chemical mediators, besides causing nasal allergic symptoms, may act as an aggravating factor in vicious cycle promoting hyperreactivity of the nasal mucosa by increasing density of muscarinic receptors.