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A distinct differential pattern of distribution of peptidergic nerves in the sphincters of rat, cat and man
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A DISTINCT SPHINCTERS London,
DIFFERENTIAL OF RAT, CAT
PATTERN AND MAN.
OF DISTRIBUTION OF PEPTIDERGIC NERVES IN THE A.E. Bishop, H. Inakuchi, J-M. Polak, R.P.M.S.
U.K.
Recent evidence shows an increase in the amount of VIP immunoreactive material in certain sphincters of the cat. We have studied, in detail, the distribution of the entire peptidergic innervation of gut sphincters in a range of mammalian species, including man. Cardiac , pyloric, ileo-caecal and anal sphincters from 6 rats and 5 cats and 5 human pyloric sphincters were studied by immunocytochemistry. Close anatomical areas, immediately proximal and distal to sphincters and regions further away, were taken for comparison. Brightly immunostained VIP nerves were seen in the mucosa, submucosa and longitudinal muscle of the rat and cat pyloric sphincters and in the rat ileo-caecal valve, in numbers comparable to those in non-sphincter areas. Interestingly a distinct differential pattern of distribution of VIP nerves was found in these three specific areas, along the inner margin of the circular muscle in the deep muscular plexus, where a substantially increased population of VIP nerves was observed. Other rat and cat sphincters, including cardiac and anal, showed no such increase in VIP nerves. Further, no increase in VIP innervation was seen in the human pyloric sphincter. In contrast to VIP, nerves containing substance P, met-enkephalin and bombesin were not increased in sphincters and had a similar distribution in each area of the gut, except for the external anal sphincter which contained no peptidergic innervation of any type, even VIP. Therefore, is we conclude that, as a rich supply of VIP nerves to sphincters not a generalised phenomenon within or across mammalian species, special attention must be paid to the detailed morphological distribution of peptidergic nerves before interpretation can be made of their functions in sphincters.
ABNORMALITIES A-E. Bishop,
OF NEURAL AND HORMONAL PEPTIDES J-M- Polak, B. Lake, M.G. Bryant
IN HIRSCHSPRUNG'S DISEASE and S.R. Bloom, RPMS, l.ondon,UK.
A severe disruption of normal gut motility exists in Hirschpsrung's disease as a result of extensive abnormalities of the autonomic innervation. Biologically active peptides, involved in the control of gut motility, are present in high concentrations in the large bowel. The possibility of an involvement of these peptides in Hirschsprung's disease was investigated by immunocytochemistry and radioimmunoassay. Surgical specimens of large bowel were taken from 8 children (ages 6 months to 2 years) and compared with age-matched controls. The diseased tissues were sampled from distinctly dilated and constricted areas and from mid or transitional portions. Conventional histology established the hypo/aganglionic areas. Both VIP and substance P nerves were greatly reduced in hypo/aganglionic areas of diseased specimens, in apparent proportion to the extent of aganglionosis. Enteroglucagon (EG) and somatostatin (som) cells were also reduced in diseased bowel. EG cells were reduced from 220227 cells/mm2 (mean+SEM) in controls to respmid and distal portions, 109+8, 176213 and 198+15 cells/mm2 in proximal, ectively. Som cells fell from 2227.7 to 7~3.2, 1022.7 and 15~3.7 in similar areas. Comparable changes were revealed by measurement of bowel peptide content eg VIP content fell from 142218 pmol/g wet weight of tissue to 69210.9 pmol/g, a range of 6.0 to 98 pmol/g depending on the extent of aganglionosis. Thus, major abnormalities of the diffuse neuroendocrine system exist in Hirschsprung's disease, indicating that a disturbance of the normal pattern of regulatory peptides is involved in the development of severely disordered gut function.
A DISTINCT SPHINCTERS London,
DIFFERENTIAL OF RAT, CAT
PATTERN AND MAN.
OF DISTRIBUTION OF PEPTIDERGIC NERVES IN THE A.E. Bishop, H. Inakuchi, J-M. Polak, R.P.M.S.
U.K.
Recent evidence shows an increase in the amount of VIP immunoreactive material in certain sphincters of the cat. We have studied, in detail, the distribution of the entire peptidergic innervation of gut sphincters in a range of mammalian species, including man. Cardiac , pyloric, ileo-caecal and anal sphincters from 6 rats and 5 cats and 5 human pyloric sphincters were studied by immunocytochemistry. Close anatomical areas, immediately proximal and distal to sphincters and regions further away, were taken for comparison. Brightly immunostained VIP nerves were seen in the mucosa, submucosa and longitudinal muscle of the rat and cat pyloric sphincters and in the rat ileo-caecal valve, in numbers comparable to those in non-sphincter areas. Interestingly a distinct differential pattern of distribution of VIP nerves was found in these three specific areas, along the inner margin of the circular muscle in the deep muscular plexus, where a substantially increased population of VIP nerves was observed. Other rat and cat sphincters, including cardiac and anal, showed no such increase in VIP nerves. Further, no increase in VIP innervation was seen in the human pyloric sphincter. In contrast to VIP, nerves containing substance P, met-enkephalin and bombesin were not increased in sphincters and had a similar distribution in each area of the gut, except for the external anal sphincter which contained no peptidergic innervation of any type, even VIP. Therefore, is we conclude that, as a rich supply of VIP nerves to sphincters not a generalised phenomenon within or across mammalian species, special attention must be paid to the detailed morphological distribution of peptidergic nerves before interpretation can be made of their functions in sphincters.
ABNORMALITIES A-E. Bishop,
OF NEURAL AND HORMONAL PEPTIDES J-M- Polak, B. Lake, M.G. Bryant
IN HIRSCHSPRUNG'S DISEASE and S.R. Bloom, RPMS, l.ondon,UK.
A severe disruption of normal gut motility exists in Hirschpsrung's disease as a result of extensive abnormalities of the autonomic innervation. Biologically active peptides, involved in the control of gut motility, are present in high concentrations in the large bowel. The possibility of an involvement of these peptides in Hirschsprung's disease was investigated by immunocytochemistry and radioimmunoassay. Surgical specimens of large bowel were taken from 8 children (ages 6 months to 2 years) and compared with age-matched controls. The diseased tissues were sampled from distinctly dilated and constricted areas and from mid or transitional portions. Conventional histology established the hypo/aganglionic areas. Both VIP and substance P nerves were greatly reduced in hypo/aganglionic areas of diseased specimens, in apparent proportion to the extent of aganglionosis. Enteroglucagon (EG) and somatostatin (som) cells were also reduced in diseased bowel. EG cells were reduced from 220227 cells/mm2 (mean+SEM) in controls to respmid and distal portions, 109+8, 176213 and 198+15 cells/mm2 in proximal, ectively. Som cells fell from 2227.7 to 7~3.2, 1022.7 and 15~3.7 in similar areas. Comparable changes were revealed by measurement of bowel peptide content eg VIP content fell from 142218 pmol/g wet weight of tissue to 69210.9 pmol/g, a range of 6.0 to 98 pmol/g depending on the extent of aganglionosis. Thus, major abnormalities of the diffuse neuroendocrine system exist in Hirschsprung's disease, indicating that a disturbance of the normal pattern of regulatory peptides is involved in the development of severely disordered gut function.