INNERVATION OF THE RAT GASTROINTESTINAL SPHINCTERS - CHANGES DURING DEVELOPMENT AND AGING

The effect of age on the adrenergic and peptidergic innervation of the Lower oesophageal, pyloric and ileocaecal sphincters of the rat was i nvestigated using immunohistochemical techniques. The distribution of nerve fibres containing the neuronal protein, growth associated protei n-43, was also studied to determine the integrity of the enteric nervo us system during development and aging. The fo ur age groups examined were 2-3 days, 6 weeks, 3 months and 25 months old rats. Using protein gene product 9.5 antibody (a non-specific general neuronal marker), i t was revealed that the myenteric ganglia in all sphincter regions wer e compactly arranged and were smaller in size at neonatal stage gettin g more spaced out and larger in size with age. There was no obvious ch ange in the structure of the neuronal elements with age. In the lower oesophageal sphincter, calcitonin gene-related peptide- and substance P-like immunoreactive nerve fibres showed notable changes in density a nd fluorescence intensity with age, decreasing and increasing, respect ively, with no obvious change in vasoactive intestinal polypeptide- an d growth-associated protein-like immunoreactivity. A slight increase i n dopamine-beta-hydroxylase-like immunoreactivity was seen in old age. In the pyloric sphincter, there was an increase in calcitonin gene-re lated peptide- and substance P-like immunoreactivity with a less notab le increase in dopamine-beta-hydroxylase-like immunoreactivity. A decr ease in vasoactive intestinal polypeptide- and growth-associated prote in-43-like immunoreactivity in the circular muscle of the sphincter wa s seen in old age, In the ileocaecal sphincter there was a marked incr ease in growth associated protein-43-, vasoactive intestinal polypepti de-, dopamine-beta-hydroxylase and substance P-like immunoreactivity. There was a decrease in the density of calcitonin gene-related peptide -like immune-reactive nerve fibres in old age. In summary, two main co nclusions can be drawn from the results of the present study. First, t here was an age-related differential change in the density of immunore active nerve fibres containing various neuroactive substances. This in dicates a level of plasticity of the various enteric nerve types and m ay reflect the degree of importance of the different neurotransmitters in the physiological activities of the specific sphincter, Second, in all three sphincters of aged rats, the density of nerve fibres contai ning the markers for the excitatory neurotransmitters noradrenaline an d substance P (although the precise role of substance P in ileocaecal sphincter is not known) was increased, while the density of nerve fibr es containing the inhibitory neurotransmitters calcitonin gene-related peptide in the lower oesophageal and possibly ileocaecal sphincter, a nd vasoactive intestinal polypeptide in the pylorus were decreased. Th is is likely to underlie the physiological activity of the sphincters and may be associated with malfunction in old age. Investigations to d etermine the functional implications of these changes would be of grea t interest.