Immunocytochemical and ultrastructural differentiation between Met- enkephalin-, Leu-enkephalin-, and Met/Leu-enkephalin-immunoreactive neurons of feline gut

Abstract

Selective immunocytochemical procedures, applied at the light and electron microscopical level, have resulted in the identification of three types of enkephalin-immunoreactive nerves in the feline gastrointestinal tract, including neurons containing either Met- or Leu-enkephalin immunoreactivity or those simultaneously storing both Met- and Leu-enkephalin immunoreactants. The three different types of enkephalin nerves show a similar distribution in the gut with the exception of the small arteries which frequently appear to be innervated only by Met-enkephalin-immunoreactive terminals. Electron microscopical identification using optimally fixed, osmicated, and contrasted tissue revealed ultrastructural differences between the three types of nerve terminals. Thus, the terminals contained variable proportions of large granular and large opaque p-type vesicles. Large granular vesicles were associated predominantly with Met-enkephalin immunoreactions. It is presently impossible to decide whether the different p-type vesicles reflect a continuous processing of a precursor contained within them or whether they are truly different in peptide content. Thus, granular vesicles had cores of either high or medium electron density. Medium electron-dense granular vesicles were sometimes difficult to distinguish from large opaque vesicles suggesting the existence of possible transitional forms. All types of enkephalin terminals also contained small clear ("cholinergic-like") vesicles which were not immunoreactive to enkephalins. These data indicate that multiple enkephalin precursors/enkephalin-containing peptides occur in the gut or, alternatively or additionally, that a common Met/Leu-enkephalin precursor is processed differently in different neurons.

A Qualitative and Quantitative Study on the Enkephalinergic Innervation of the Pig Gastrointestinal Tract

“…It has been established on the basis of ultrastructural data that synaptophysin labels the small clear vesicles present in nerve fibers (Navone et al 1986). On the other hand, the ENK-IR fibers in the cat digestive tract are characterized by the presence of both large, dense ENK-IR vesicles and small, clear non-ENK-IR vesicles (Larsson and Stengaard-Pedersen 1982). This set of structural data makes it possible to compare the enkephalinergic innervation with the intramural innervation of the digestive tract as a whole, i.e., that which can be determined by performing synaptophysin labeling.…”

Role of Opioid Ligands in the Irritable Bowel Syndrome

“…Along the paleospinothalamic pain pathway, mu, delta and kappa receptors have been found at the level of the spinal cord, the periaqueductal grey matter, the thalamus and the cerebral cortex. In the periphery, opioid receptors have been localized in the myenteric and submucosal plexuses (6,7). An interesting experimental model that illustrates the complex brain-gut relationship as well as the different effects and sites of actions of the subtypes of opioids is ileus produced by surgical procedure or peritonitis, which elicits pain and gastrointestinal (GI) motor inhibition; the effect on GI motor activity is mediated by a peritoneogastrointestinal inhibitory reflex with the involvement of afferent splanchnic nerves, hypothalamic release of corticotropin-releasing factor (CRF) and efferent vagal fibres.…”

Biological redundancy of endogenous GPCR ligands in the gut and the potential for endogenous functional selectivity

“…Enkephalin-derived peptides are mainly found in the cell bodies of myenteric neurons and in nerve fibers within the myenteric plexus and circular muscle ( Elde et al, 1976 ; Jessen et al, 1980 ; Schultzberg et al, 1980 ; Furness et al, 1983 ). There is evidence that immunoreactivities for Leu-enk and Met-enk are expressed by distinct neuronal populations within the enteric nervous system ( Linnoila et al, 1978 ; Larsson et al, 1979 ; Larsson and Stengaard-Pendersen, 1982 ). The morphology and distribution of Enk-containing myenteric neurons has been examined in detail.…”