Quinacrine-induced dilation of the rat cecum and degeneration of large granular vesicle-containing neurons in the myenteric plexus

Summary

Intraperitoneal injection of quinacrine (100 mg/ kg) into rats causes marked dilation of the cecum about one week after the injection, but the jejunum remains its normal size. The morphological changes induced in the myenteric plexus and the longitudinal and circular muscle layers of both the cecum and the jejunum have been examined by fluorescence and electron microscopy 1.5 h to 2 weeks after the injection.

In the cecum, 1.5 h after the injection, the granular fluorescence of quinacrine was apparent in many ganglion cells of the myenteric plexus and in the nerve fibers in the muscle layers. In connection with the granular fluorescence, numerous lysosomal dense bodies appeared in ganglion cells and axons, and subsequently the degeneration of the neurons was observed at ultrastructural level. The lysosomal dense bodies often contained many large granular vesicles of 95–140 nm in diameter. The number of lysosomal dense bodies in the axons was greatest 3–7 days after the injection. Although the axon type sensitive to quinacrine could not be specified, axons containing many large granular vesicles were the predominate type. Fibrosis in the outer longitudinal muscle layer was another characteristic resulting from quinacrine administration. Proliferation of the rough-surfaced endoplasmic reticulum and of the Golgi complex and a concomitant decrease in the number of myofilaments became evident in many smooth muscle cells 3–7 days after the injection; the intercellular spaces became enlarged 7 days after quinacrine administration. These changes and the dilation of the cecum showed considerable recovery 2 weeks after the injection. A similar distribution of quinacrine fluorescence, lysosomal dense bodies and fibrosis were found in the jejunum, though in lesser degree. We suggest that the neuronal and/or muscular alterations are prerequisites for the enlargement of the cecum and that the regional difference of the gut in terms of sensitivity to quinacrine is quantitative rather than qualitative.