EFFECT OF CELIAC GANGLIONECTOMY ON TACHYKININ INNERVATION, RECEPTOR DISTRIBUTION AND INTESTINAL RESPONSES IN THE RAT

Substance P (SP) is an important neurotransmitter in the control of in testinal motility and is found in both the enteric and sympathetic ner vous systems. This study examined the effect of celiac ganglionectomy on (1) mechanical properties of the circular muscles of the duodenum, ileum and proximal colon, (2) circular muscle responses to SP and neur okinin A, (3) distribution of substance P-like immunoreactive nerves, and 4) the distribution of neurokinin 1 and neurokinin 2 receptors. Ce liac ganglionectomy resulted in an effective sympathectomy as evidence d by a marked decrease in norepinephrine content and tyrosine hydroxyl ase staining in the duodenum, ileum and proximal colon. The in vitro l ength/tension characteristics of the circular muscle of the duodenum, ileum and colon were unchanged after ganglionectomy. In all regions of the gut studied, substance P and neurokinin A caused dose-dependent c ontractions that were unaltered by celiac ganglionectomy. Immunohistoc hemistry revealed moderate substance P-like immunoreactive fibers in t he myenteric plexus, submucosal plexus and circular muscle of the ileu m, while in the colon, substance P-like immunoreactivity was intense i n the myenteric plexus, and moderate in the circular muscle. In vitro autoradiography showed minimal binding of SP (NK1 receptor) or neuroki nin A (NK2 receptor) in the ileum and significantly greater binding in the circular muscle layer of the colon. Celiac ganglionectomy did not affect substance P-like immunoreactivity, or NK1 or NK2 receptor bind ing. A greater contractile response to neurokinins was seen in the col on than in the duodenum or ileum, which paralleled the receptor densit y. The studies demonstrate that surgical celiac ganglionectomy, unlike chemical sympathectomy, does not affect the substance P innervation, receptor density or physiological responses of the intestine. The grea ter contractile response of the colon than the ileum parallels the gre ater receptor density rather than the peptide content as determined by immunhistochemistry.