Neuronal cholecystokinin, gastrin-releasing peptide, neurotensin, and beta-endorphin in the intestine of the guinea pig. Distribution and possible motor functions

Abstract

The guinea-pig intestine was found to harbor nerve fibers containing immunoreactive cholecystokinin (CCK), gastrin-releasing peptide (GRP), neurotensin or beta-endorphin. Such fibers occurred in the myenteric and submucous ganglia and in the smooth muscle. GRP- and CCK-fibers, in addition, were found in the mucosa. Following colchicine treatment, neuronal perikarya in the myenteric ganglia displayed CCK-, GRP-, or beta-endorphin immunoreactivity. CCK-immunoreactive perikarya were located also in the submucous ganglia. Neurotensin-immunoreactive cell bodies could not be detected. The presence of immunoreactive neuronal perikarya in intramural ganglia indicates that CCK-, GRP- and beta-endorphin-containing fibers are intrinsic to the gut wall. GRP, neurotensin, and beta-endorphin were identified in extracts of smooth muscle by immuno-chemical and chromatographic analysis. CCK-8, GRP and neurotensin contracted the isolated taenia coli. Tetrodotoxin reduced the response to CCK-8 but not that to GRP and neurotensin, suggesting that the two latter peptides act directly on smooth muscle receptors. The effect of CCK-8 is partly mediated by cholinergic nerves, since not only tetrodotoxin but also atropine greatly reduced the CCK-8-induced contractile response. The substance P (SP) antagonist, (D-Pro2, D-Trp7,9)-SP1-11 had no effect on the CCK-8-induced contraction of the taenia. CCK-8 enhanced the SP-mediated (atropine-resistant) contractile response to electrical stimulation but not that mediated by acetylcholine. beta-Endorphin had no effect on the tension of the muscle but reduced the response to electrical stimulation (cholinergic as well as SP-mediated) through a naloxone-sensitive mechanism. While CCK-8 and beta-endorphin seem to play neuromodulatory roles in the taenia coli, the significance of GRP and neurotensin remains enigmatic.