Effects of extrinsic autonomic inputs on expression of c-Fos immunoreactivity in myenteric neurons of the guinea pig distal colon.

c-Fos protein is a nuclear protein coded by c-fos proto-oncogene subsequent to synaptic activation of the neurons. We used immunohistochemical methods to visualize the expression of c-Fos protein in myenteric neurons of the guinea pig distal colon and examined the effects of the extrinsic autonomic inputs on the enteric circuits. No c-Fos immunoreactivity was observed in the colonic segments fixed immediately after removal from the animal body. A number of c-Fos-immunoreactive nuclei of myenteric neurons, however, appeared in all preparations that were incubated in Krebs solution in vitro (n=10). Application of tetrodotoxin (0.2 microM) abolished the expression of c-Fos-immunoreactivity (n=6), but hexamethonium (100 microM) failed to decrease the number of c-Fos-positive neurons despite a complete suppression of spontaneous peristaltic movements (n=5). Neither the electrical stimulation (n=8) nor the severing of the pelvic nerves (n=5) changed the number of c-Fos-positive neurons. Application of clonidine, an alpha(2)-agonist, (0.1 microM) abolished the expression of c-Fos protein in all preparations (n=5), while denervation of the sympathetic fibers in the lumbar colonic and hypogastric nerves in vivo increased the number of c-Fos-positive neurons (n=5). The results indicate that the enteric circuit in the distal part of the gastrointestinal tract is under tonic inhibition by the sympathetic nervous system from the lumbar spinal cord. c-Fos immunoreactivity expressed in the colonic preparations in vivo might be the results of enhanced activation of non-nicotinic receptors after removal of the sympathetic inhibition. Copyright 2002 Elsevier Science B.V.