Abstract
The release of dynorphin-(1-17), somatostatin and substance P into the venous effluate of the isolated and vascularly perfused guinea-pig small intestine was measured during rest and peristaltic activity. The peptides were determined by specific radioimmunoassays. Increasing the intraluminal pressure by 5 mbar increased the release of dynorphin-(1-17), somatostatin and substance P. A substantial increase in the release of substance P was only seen in the presence of naloxone (1.5 microM) indicating an inhibitory influence of opioid peptide-containing neurones on the release of substance P. The pressure-induced release of substance P and dynorphin-(1-17) was completely prevented by tetrodotoxin (1.3 microM), which suggests a neural origin of these two peptides. The pressure-induced release of somatostatin was only partially inhibited by tetrodotoxin (1.3 microM) suggesting that somatostatin may also be released from non-neuronal sources, i.e. endocrine mucosal cells. Dimethylphenylpiperazinium (32 microM) increased the release of somatostatin and substance P and this effect was inhibited by tetrodotoxin (1.3 microM). Cholecystokinin-octapeptide (38 nM) induced a large increase in the release of somatostatin but only a minute increase in the release of substance P; these effects of cholecystokinin-octapeptide were not blocked by tetrodotoxin (1.3 microM). Noradrenaline (59 microM) inhibited the pressure-induced release of substance P but not that induced by dimethylphenylpiperazinium (32 microM). Neither the pressure-induced nor the dimethylphenylpiperazinium-evoked release of somatostatin was significantly diminished by noradrenaline. These results indicate that dynorphin-(1-17), somatostatin and substance P may be transmitters involved in the coordination of the peristaltic reflex. Part of the inhibitory effects of opioid peptides and noradrenaline on intestinal motility may be brought about by inhibition of the release of substance P.