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Distribution and Colocalization of Nitric Oxide Synthase and Calretinin in Myenteric Neurons of Developing, Aging, and Crohn's Disease Human Small Intestine

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Abstract

The pattern of distribution and colocalizationof nitric oxide synthase and the calcium-binding proteincalretinin in myenteric neurons and nerve fibers wereexamined in the human small intestine from preterm fetuses (14-17 weeks of gestation), normaladults (mean age 50 years old), old age (mean age 80years old), and Crohn's disease patients (mean age 30years old) using NADPH-diaphorase histochemistry and immunohistochemical techniques. In all agegroups investigated, NADPH-diaphorase-reactive andcalretinin-immunoreactive neurons and nerve fibers wereseen throughout the myenteric plexus. The highestproportion of NADPH-diaphorase-reactive neurons was foundin the myenteric ganglia of old age intestines (56% ofprotein gene product-immunoreactive neurons) followed byfetal intestines (41%) and Crohn's intestine (30%) compared with intestines of controladults (20%). A similar trend was observed forcalretinin-immunoreactive neurons where the highestproportion of immunoreactive neurons was found in themyenteric ganglia of old age intestines (28% of proteingene product-immunoreactive neurons), followed by fetalintestines (22%), and Crohn's intestines (18%) comparedwith intestines of control adults (9%). A colocalization of NADPH-diaphorase activity and calretininimmunoreactivity was only seen in the myenteric neuronsof fetal intestines (2% of NADPH-diaphorase-reactiveneurons were also calretinin-immunoreactive). The pattern of distribution of NADPH-reactive andcalretinin-immunoreactive neurons in the myentericganglia of fetal intestine differs from that of theother age groups. In the fetal intestine, the myenteric neurons containing either calretinin orNADPH-diaphorase are distributed through out themyenteric ganglia with no specific orientation to oneanother. In the intestines of control adult, Crohn's,and old age patients, single largecalretinin-immunoreactive neurons are surrounded by anumber of small NADPH-diaphorase-positive neurons, withthis feature being more prominent in intestines ofold-age and Crohn's disease patients. In summary, a high number ofboth NADPH-diaphorase-reactive andcalretinin-immunoreactive neurons were seen in themyenteric ganglia of fetal, old age, and Crohn'sintestines; we discuss that there may be a role for nitric oxide andcalretinin in the process of development, aging, andpathological changes in the human intestine associatedwith alteration in the calcium homeostasis in the myenteric neurons.

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Belai, A., Burnstock, G. Distribution and Colocalization of Nitric Oxide Synthase and Calretinin in Myenteric Neurons of Developing, Aging, and Crohn's Disease Human Small Intestine. Dig Dis Sci 44, 1579–1587 (1999). https://doi.org/10.1023/A:1026658826010

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