Regional variation in the neurochemical coding of the myenteric plexus of the human colon and changes in patients with slow transit constipation

Abstract

There are differences in the structure and function between regions of the colon. In patients with slow transit constipation the activity of all regions is markedly slowed. Counts of colonic neurones in slow transit constipation have been semiquantitative and led to varying results. We have applied new methods of quantification of markers in whole mounts of the colonic myenteric plexus to compare density of innervation between regions and between normal patients and those undergoing resection for severe constipation. Whole mounts of colonic myenteric plexus were made from specimens removed for cancer treatment (controls) and cases of severe constipation. All neurones were labelled by anti-human neuronal protein antibodies. Neurones synthesizing acetyl choline were labelled for choline acetyltransferase (ChAT) and those for nitric oxide by antisera to nitric oxide synthase (NOS). Four populations of neurones were distinguished and quantified according to the two selective markers, ChAT and NOS. In the normal major populations were NOS alone (51% of ascending colon neurones and 44% of descending colon neurones) and ChAT alone (41% ascending colon, 48% descending colon). Nitric oxide synthase/ChAT and NOS-/ChAT-comprised only small populations. In all regions in severe constipation, the percentage of NOS-only colonic myenteric neurones was raised (54% ascending colon, 49% descending colon) and ChAT only was reduced (36% ascending colon, 42% descending colon). The other populations were not changed. Accurate quantification of neuronal populations in whole mounts of human colon reveals inter-regional differences in innervation and marked changes in innervation in cases of very severe constipation.

Cyclooxygenase-Dependent Alterations in Substance P-Mediated Contractility and Tachykinin NK1 Receptor Expression in the Colonic Circular Muscle of Patients with Slow Transit Constipation

“…Conversely, increased NO synthase-positive neurons and activities are associated with STC (Tomita et al, 2002;Wattchow et al, 2008). Our result is in agreement with the study by Mitolo-Chieppa et al (2001) performed in male STC circular muscle, which shows that EFS-induced relaxation of SP-precontracted muscle strips is reduced at 0.5 Hz (ATP mediated) and enhanced at 4 Hz (NO) medicated compared with control, suggesting an abnormality in NO and ATP release.…”

“…3 H]ACh in response to EFS in STC taenia coli muscle strips and decreased choline acetyltransferase in colonic myenteric neurons of STC have been demonstrated (Burleigh, 1988;Wattchow et al, 2008). Conversely, increased NO synthase-positive neurons and activities are associated with STC (Tomita et al, 2002;Wattchow et al, 2008).…”

Characterization of motor patterns in isolated human colon: are there differences in patients with slow-transit constipation?

“…There is also evidence that the interval between CMCs is reduced in the transverse colon and splenic flexure (9). Other studies have demonstrated reductions in specific neurochemical classes of myenteric neurons in STC patients (4,15,21,32), in addition to reduced density of pacemaker cells (16) or specific types of neuromuscular transmission (31). Whether anatomical or functional changes in the large intestine of STC patients represents a cause or an effect of STC is not fully clear.…”

Impaired colonic motility and reduction in tachykinin signalling in the aged mouse

“…Moreover adecrease in cholineacetyltransferasepositive neurons and arelative increase in the percentage of nitric oxide synthase positive neurons have been demonstrated in middle-aged aged adults suffering from slow-transit constipation (Wattchow et al, 2008). However, a reduction in myenteric neuronal number is also seen in humans with no detectable GI disorders and therefore their involvement in age-related constipation is questionable (Bernard et al, 2009).…”