Leukotriene-C 4 enhances mucus production from submucosal glands in canine trachea in vivo

Abstract

Because leukotrienes have been implicated as putative mediators in upper airways disease, we studied whether leukotriene C 4 (LTC 4) might also have a mucus enhancing effect on submucosal glands. We anesthetized mongrel dogs with chloralose (100 mg/kg) and urethane (500 mg/kg) and ventilated them on a pump. To help visualize the secretions from submucosal glands, we exposed the mucosa of the upper trachea and coated its surface with powdered tantalum. Secretions from the glands (hillocks) were measured with time: The number of hillocks was measured at four time points on 19 dogs after each treatment in the sequence: no LTC 4, LTC 4, no LTC 4 and LTC 4 + blocker. The potential blockers were nerve cutting, atropine, FPL-55, 712, and hexamethonium. Each potential blocker was used on 3–5 dogs. LTC 4 was injected into the cranial thyroid artery. In 19 dogs with 27 responses, LTC 4(8.6–11.0 μg) gave a positive response that was significantly different from control ( P < 0.01) at 1–4 min. These effects were not abolished in 5 dogs by cutting the superior laryngeal (SLN) and the vagus nerves ( P < 0.01). Pretreatment of the dogs ( n = 5) with atropine, hexamethonium and the specific SRS-A (LTC 4) antagonist FPL 55,112 ( n = 3) gave a significant ( P < 0.01–0.05) reduction in mucus secretion at all times for atropine, hexamethonium, and at all times except 4 min for (FPL 55,712). These results indicate that leukotriene C 4 induces mucus secretion in dogs. This secretion does not depend on an intact reflex pathway but is altered at the individual gland by agents which block ganglionic motor pathways.