Localization of substance P (SP)-immunoreactivity in the myenteric plexus of the rat esophagus.

The present immunohistochemical study was performed to examine the number, distribution, and chemical coding of intrinsic substance P (SP) neurons and nerve fibers within the esophagus and discuss their functional roles. Many SP neurons and nerve fibers were found in the myenteric plexus, and the SP neurons gradually decreased from the oral side toward the aboral side of the esophagus. Double-immunolabeling showed that most SP neurons were cholinergic (positive for choline acetyltransferase), and few were nitrergic (positive for nitric oxide synthase). Some cholinergic SP nerve terminals surrounded cell bodies of several myenteric neurons. In the muscularis mucosa and lower esophageal sphincter, and around blood vessels, numerous SP nerve endings were present, and many of them were cholinergic. Also, SP nerve endings were found on only a few motor endplates of the striated muscles, and most of them were calcitonin gene-related peptide (CGRP)-positive. Retrograde tracing using Fast Blue (FB) showed that numerous sensory neurons in the dorsal root ganglia (DRGs) and nodose ganglion (NG) projected to the esophagus, and most FB-labeled SP neurons were CGRP-positive. These results suggest that the intrinsic SP neurons in the rat esophagus may play roles as, at least, motor neurons, interneurons, and vasomotor neurons, which are involved in local regulation of smooth muscle motility, neuronal transmission, and blood circulation, respectively. Moreover, SP nerve endings on only a minority of motor endplates may be extrinsic, derived from DRGs or NG, and possibly detect chemical circumstances within motor endplates to modulate esophageal motility.