EFFECTS OF ANTIBODIES AGAINST ACETYLCHOLINESTERASE ON THE EXPRESSION OF PEPTIDES AND CATECHOLAMINE-SYNTHESIZING ENZYMES IN THE RAT ADRENAL-GLAND

In the rat, systemic administration of murine monoclonal antibodies ag ainst acetylcholinesterase caused rapid piloerection and ptosis (withi n 30-60 min after the injection). Using indirect immunohistochemistry the effect of these antibodies on peptides and enzyme expression was s tudied in the rat adrenal gland. Four days after antibody administrati on a total disappearance of acetylcholinesterase-immunoreactive fibers was observed. However, groups of acetylcholinesterase-immunoreactive chromaffin cells and intramedullary ganglion cells, both cell types sh owing acetylcholinesterase immunoreactivity also in the control adrena l medulla, expressed increased immunoreactivity. Analysis revealed tha t the acetylcholinesterase-immunoreactive chromaffin cell groups lacke d phenylethanolamine-N-methyltransferase staining both in controls and treated rats. Antibody administration also affected levels of several peptides present in nerve fibers and chromaffin cells. Thus, the numb er of cells expressing enkephalin, calcitonin gene-related peptide and galanin was dramatically increased compared to the very few cells obs erved containing these three peptides in the normal gland. The majorit y of cells expressing enkephalin after antibody treatment also showed phenylethanolamine-N-methyltransferase immunoreactivity. In contrast, the few chromaffin cells expressing strong enkephalin-like immunoreact ivity in controls were phenylethanolamine-N-methyltransferase negative . The sparse networks of calcitonin gene-related peptide- and galanin- positive fibers found in control adrenals were unchanged after the ant ibody treatment. However, the dense network of enkephalin varicose fib ers totally disappeared after the antibody injection. A few substance P- and somatostatin-immunoreactive cells, not present in the normal gl and, appeared after administration of the antibodies, whereas no chang es were encountered with regard to immunoreactive nerve fibers. No cle ar differences between normal and treated animals could be observed in chromaffin cells with regard to immunoreactivity for neuropeptide Y o r any of the four catecholamine-synthesizing enzymes, tyrosine hydroxy lase, aromatic 1-amino acid decarboxylase, dopamine beta-hydroxylase o r phenylethanolamine-N-methyltransferase. The present findings demonst rating a disappearance of acetylcholinesterase- and enkephalin-immunor eactive nerve fibers in the adrenal gland after intravenous injection of acetylcholinesterase antibodies support earlier reports showing tha t these antibodies cause degeneration of preganglionic fibers, and tha t neuronal decentralization of the adrenal gland induces marked increa ses in the levels of several peptides in chromaffin cells.