ACETYLCHOLINE IN ISOLATED AIRWAYS OF RAT, GUINEA-PIG, AND HUMAN - SPECIES-DIFFERENCES IN ROLE OF AIRWAY MUCOSA

Stored endogenous acetylcholine (ACh) and in vitro synthesis of [H-3]A Ch were measured in isolated, mucosa-intact and mucosa-denuded airways of rat, guinea pig, and humans. In addition, choline acetyltransferas e (ChAT) activity and ACh content were measured in freshly isolated ai rway mucosa as well as in cultured epithelial cells of rat tracheas. R at tracheas stored 25 nmol/g ACh, whereas guinea pig tracheas and huma n bronchi contained only 2-3 nmol/g ACh. When incubated with [H-3] cho line, the isolated airways of rat, guinea pig, and human synthesized s ignificant amounts of [H-3]ACh. In guinea pig and human airways, remov al of the mucosa affected neither stored ACh nor in vitro synthesis of [H-3]ACh. In rat tracheas, however, removal of the mucosa resulted in a 50% reduction of stored ACh. Freshly isolated mucosa wiped off from the luminal surface of rat tracheas contained large amounts of ACh (6 .5 nmol/g airway), whereas in human mucosa (central bronchi) only smal l amounts of ACh were found. In enzymatically isolated mucosal cells o f rat tracheas, a considerable ChAT activity (21 nmol . mg protein(-1) . h(-1)) was detected, blockable by bromoacetylcholine. Enzymatically isolated human mucosa contained a rather low ChAT-like activity (0.5 n mol . mg protein(-1). h(-1)), not sensitive to bromoacetylcholine. In cultured epithelial cells of rat tracheas (4th-6th passage), neither C hAT activity nor ACh was detected. The large airways of rat, guinea pi g, and humans contain considerable amounts of ACh, supporting histolog ical evidence of a dense cholinergic innervation particularly of rat t racheas. The mucosa of rat tracheas synthesizes and stores large amoun ts of ACh, whereas the low ChAT activity in human mucosa argues agains t the presence of cholinergic neurons able to synthesize and store ACh .