NADPH-diaphorase-positive nerve fibers associated with motor endplates in the rat esophagus: new evidence for co-innervation of striated muscle by enteric neurons

Abstract

NADPH-diaphorase histochemistry was combined with demonstration of acetylcholinesterase and immunocytochemistry for calcitonin gene-related peptide to study esophageal innervation in the rat. Most of the myenteric neurons stained positively for NADPH-diaphorase, as did numerous varicose nerve fibers in the myenteric plexus, among striated muscle fibers, around arterial blood vessels, and in the muscularis mucosae. A majority of motor endplates (as demonstrated by acetylcholinesterase histochemistry or calcitonin gene-related peptide immunocytochemistry) were associated with fine varicose NADPH-diaphorase-positive nerve fibers. Analysis of brainstem nuclei, sensory vagal, spinal, and sympathetic ganglia in normal and neonatally capsaicin-treated rats, and comparison with anterogradely labeled vagal branchiomotor, preganglionic and sensory fibers led to the conclusion that NADPH-diaphorase-positive fibers on motor endplates originate in esophageal myenteric neurons. No association of NADPH-diaphorase-positive nerve fibers with motor endplates was found in other organs containing striated muscle. These results suggest extensive, presumably nitrergic, co-innervation of esophageal striated muscle fibers by enteric neurons. Thus, control of peristalsis in the esophagus of the rat may be more complex than hitherto assumed.

A novel pathogenesis of megacolon in Ncx/Hox11L.1 deficient mice.

“…Thus, functions of the ganglia were analyzed by examining the production of NADPH diaphorase and substance P in the neuronal cells. NADPH diaphorase is identical to nitric oxide synthase (26)(27)(28)(29) and nitric oxide functions as an inhibitory neurotransmitter to relax smooth muscle (30), while substance P is an excitatory neurotransmitter to contract circular smooth muscles (31,32). NADPH diaphorase positive neuronal cells were dense in the proximal colon of Ncx Ϫ / Ϫ mice with (data not shown) or without megacolon (Fig.…”

Evidence for the involvement of neurotrophins in muscle transdifferentiation and acetylcholine receptor transformation in the esophagus of Myf5−/−:MyoD−/− and NT‐3−/− embryos

“…Considering that the motor endplates of striated esophageal muscle, unlike other striated muscles, have both the vagal and the enteric innervation (Neuhuber et al, 1994;Wö rl et al, 2002), it appears probable that the innervation has a function in smooth-to-skeletal muscle transition. To assess possible differences in innervation between the wild-type and Myf5 -/-:MyoD -/-mouse esophagi, we used histochemistry and various immunohistochemical markers for vagal and enteric innervation on relevant embryonic stages (i.e., E15.5-E18.5).…”

“…Therefore, the motor endplates of striated esophageal muscle, unlike other striated muscles, have both the regular (i.e., vagal) cholinergic innervation, but also a coinnervation by nerves from the ENS (Neuhuber et al, 1994), reaching a maximum of 80% coinnervation at P4 and then progressively declining for several months (Wö rl et al, 2002). Although it is possible that this enteric coinnervation might be residual from the SM cells preceding the supposed transdifferentiation, the precise timing of innervation and removal of the enteric neurons around the formation of the motor endplates has led to the conclusion that this coinnervation likely has a perinatal function in maintenance or development of striated muscle in the mouse esophagus (Neuhuber et al, 1994;Wö rl et al, 2002).…”

Muscularis mucosae - the forgotten sibling

“…The rat esophageal muscularis mucosae may be sparsely innervated by inhibitory adrenergic nerves. The rat esophageal muscularis mucosae is known to receive a nitrergic innervation Neuhuber et al, 1994). The electrically-evoked relaxation of the pre-contracted muscularis mucosae from the cervical esophagus was inhibited by the pretreatment with tetrodotoxin but enhanced with L-arginine.…”