Immunohistochemical localization of substance P NK1 receptor in guinea pig distal colon

Background: Neurokinin receptors facilitate tachykinin mediated intestinal motility and secretion. Distribution of Substance P (SP) neurokinin 1 receptor (NK1r) immunoreactivity (IR) has been previously characterized in guinea pig ileum, but not colon. This study localizes NK1rs in guinea pig distal colon. Methods: Neurons were double labelled for NK1r and either acetylcholine transferase (ChAT), calbindin (calb), neuropeptide Y (NPY), nitric oxide synthase (NOS) or SP. The NK1r endocytosis was induced by 10−5 mol L−1 SP, septide, [SarMet] SP or neurokinin A. Results: In guinea pig distal colon, NK1r–IR was present on 70% of submucosal neurons. Sixty‐threepercent of the NK1r–IR submucosal neurons were ChAT–IR, 16% calb/SP–IR, 19% NPY–IR and 14% NOS–IR neurons. The NK1r–IR was present on 5% of myenteric neurons. Of these 63% were ChAT–IR, 16% calb–IR neurons and 25% NOS–IR. The NK1rs were also on myenteric plexus interstitial cells of Cajal and on circular muscle. Conclusion: In guinea pig distal colon, NK1rs were on 70% of submucosal neurons including all three secretomotor neuron subtypes and sensory neurons, suggesting NK1rs have a major role in neuronal control of mucosal reflexes. The NK1rs were on few myenteric neurons but were dense on muscle cells, suggesting NK1rs affect motility through neuro‐muscular rather than neuro‐neuronal transmission.