Tachykinin and calcitonin gene-related peptide immunoreactivities and mRNAs in the mammalian enteric nervous system and sensory ganglia.

Tachykinins and CGRP label two distinct populations of neurons innervating the digestive system: intrinsic and extrinsic, afferents. The bulk of SP/tachykinin innervation originates from intrinsic neurons, even though a minor component of this innervation derives from afferent neurons, which are mostly located in dorsal root ganglia. Afferent SP/tachykinin fibers are mainly confined to a perivascular location and to the submocosa in the gut, but are distributed also to the hepatobiliary pathway and pancreas. On the contrary, the extrinsic CGRP-containing afferents form a major component of the sensory innervation of the alimentary tract, including the rich CGRP innervation of the esophagus, stomach, hepatobiliary tract, pancreas, and vasculature, as well as a portion of non-vascular fibers distributed to the intestinal wall. Tachykinin and CGRP immunoreactivities appear to be colocalized in a population of nerve fibers, which are likely to be extrinsic, afferent, since colocalization of these peptide immunoreactivities has not been reported in intrinsic neurons. The presence of SP/NKA-encoding transcripts in the enteric nervous system and sensory ganglia and the lack of hybridization signal with RNA probes complementary to NKB mRNA indicate that the PPT I gene, but not the PPT II gene, is transcribed in these structures. This observation, along with receptor binding sites and radioimmunoassay data, which have failed to detect NKB receptor binding sites or immunoreactivity (Eysselein et al., 1990; Maggio, 1988; Mantyh et al., 1988; 1989) in the intestine of several mammals, is consistent with a differential expression of the two PPT genes in the periphery and in the central nervous system (Brecha et al., 1989; Warden and Young, 1988). A differential expression of the tachykinin-encoding genes, the existence of multiple tachykinin receptor subtypes (Mantyh et al., 1988; 1989), and the findings that tachykinins can be differentiated on the basis of the potency of their activities (Galligan et al., 1987; Maggio, 1988), support the possibility that each tachykinin is expressed in separate, and perhaps functionally distinct neuronal systems. alpha- and beta-CGRP genes also are differentially expressed according to the neuronal populations: alpha-CGRP mRNA is the most prominent form in sensory ganglia, and beta-CGRP mRNA is the only form detected in enteric neurons (Mulderry et al., 1988; Sternini and Anderson, 1990). In addition, distinct distributions of mRNAs generated from the two CGRP genes have been reported in the central nervous system (Amara et al., 1985). The differential expression patterns of alpha- and beta-CGRP mRNAs are consistent with a differential regulation of the alpha- and beta-CGRP genes.(ABSTRACT TRUNCATED AT 400 WORDS)