Regulatory peptides

SUMMARY The peptidergic innervation of the gastrointestinal tract was clearly affected in these six cases of Feline Dysautonomia. Most notably there was a striking depletion of VIP‐immunoreactivity. However, the lesions in Feline Dysautonomia are not selective for neurons containing this particular peptide, since a reduction in substance P‐ and Met‐enkephalin‐immunoreactivity was also found. Depletion of these three neuropeptides does not correlate well with the clinical finding of gastrointestinal atony, since only substance P has excitatory actions on gut smooth muscle (Iversen, 1982). Both VIP and enkephalin have inhibitory actions, acting directly on smooth muscle or via the myenteric plexus respectively (Fahrenkrug and Emson, 1982; North and Egan, 1982). However, as there was no specificity in the distribution of lesions, at least in terms of peptidergic nerves, it is probable that other types of nerves in the intrinsic and extrinsic innervation of the gut are affected, and contribute to the loss of tone. The depletion of neuropeptide immunoreactivity does not distinguish between a loss of peptidergic neurons and a loss of peptide content. However, in routinely stained sections there was little evidence of neuronal loss: only a small number of abnormal, apparently degenerating, nerve cell bodies was seen in the enteric plexuses. Thus, it is possible that levels of immunoreactive materials are reduced in peptidergic nerves. At the ultrastructural level, Griffiths and Sharp (1983) have found disorganized rough endoplasmic reticulum and a depletion of ribosomes in neurons from affected cats, and it is possible that impaired peptide synthesis may contribute to the observed reduction in immunoreactivity. In contrast to the findings in the peptidergic innervation, the peptide‐containing endocrine cells appeared to be unaffected. At least, glucagon‐and somatostatin‐IR cells in the colon were not depleted in number. Thus, in Feline Dysautonomia, while there was little evidence of neuronal lesions in the gastrointestinal tract on routine histological examination, there was a marked loss of neuropeptide immunoreactivity. Neuropeptide immunohistochemistry would appear, therefore, to be more sensitive in detecting neuronal abnormalities in this disease. At present however, it cannot be used as a diagnostic tool for Feline Dysautonomia, as regulatory peptides are known to be involved in several other diseases of the mammalian gastrointestinal tract (Vaillant and others, 1982; Bloom and Polak, 1982). Further studies are required to distinguish the enteric neuropeptide abnormalities in Feline Dysautonomia from those occurring in other disorders affecting the feline gut.