Nitric oxide synthase-containing neurons in the pig large intestine: topography, morphology, and viscerofugal projections.

The distribution of neurons that are capable of synthesizing nitric oxide (NO) has been demonstrated in the porcine large intestine by means of NO synthase (NOS) immunocytochemistry and nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochemistry. An overall colocalization of NOS immunoreactivity and NADPHd staining was observed. Nitrergic neurons were abundant in the myenteric and outer submucous plexus of the caecum, colon, and rectum. Only a few nitrergic perikarya were seen in the inner submucous plexus of the colon and caecum, whereas a substantially larger number was observed in the rectum. Nitrergic nerve fibers were present in the three ganglionic nerve plexuses. Contrary to the outer longitudinal muscle layer and the mucosal region, the circular muscle layer received a dense nitrergic innervation. The nitrergic nerve cells were variable in size and shape, and several displayed vasoactive intestinal polypeptide (VIP) immunoreactivity (IR). Retrograde tracing studies revealed the existence of nitrergic neurons that project to the caudal (inferior) mesenteric ganglion. They were observed in the myenteric and outer submucous plexus of the transverse and descending colon and the rectum. These observations strongly suggest that several subpopulations of NO-synthesizing neurons, namely, motor neurons and interneurons, should be distinguished in the porcine large intestine, thereby emphasizing the importance of NO as a biologically active mediator.