The effects of gossypol on the ultrastructure and function of tracheal ciliated cells

Gossypol acetic acid inhibits rabbit tracheal ciliary function in a concentration dependent manner. At concentrations of both 10(-4)M and 5 X 10(-5), ciliary beat is reduced to less than 2 beats/sec in approximately 60 min. At 10(-5)M, reduction of frequency is more gradual, requiring 120 min or longer to approach inhibition. The primary site in the cell showing morphological alteration is the mitochondrion, although extended exposure at lower concentrations does seem to cause increase in the amount of endoplasmic reticulum and Golgi. At the time of inhibition of ciliary beat, mitochondria have a washed out matrix, disrupted cristae and extensive infolding of the outer membrane. Some indication of mitochondrial swelling is also evident. Demembranated axonemes exposed to gossypol show the same dose-dependent response as intact ciliated cells. At 10(-4)M gossypol, axonemes are completely inhibited from reactivation. Axonemes can be reactivated in the presence of 10(-5)M gossypol but are quickly inhibited. 10(-6)M gossypol has no inhibitory effect on demembranated axonemes or intact ciliated cells. Gossypol may be acting initially as a direct but reversible inhibitor of axonemal function while damage to mitochondria may be responsible for the long term, non-reversible inhibition of ciliary function.