ON THE PEPTIDERGIC HYPOTHESIS FOR NONADRENERGIC NONCHOLINERGIC INNERVATION IN THE RAT DUODENUM

1 The nature of the non-adrenergic, non-cholinergic (NANC) transmitter was studied in vitro in the rat duodenum, by use of an isometric-isov olumic preparation. 2 Electrical field stimulation (EFS) induced a tet rodotoxin (TTX)-sensitive fall both in luminal pressure and in isometr ic tension. 3 Neurotensin (NT) induced TTX-insensitive inhibitory resp onses similar to those induced by EFS. Vasoactive intestinal peptide ( VIP) caused a delayed, slow, concentration-dependent, TTX-insensitive inhibitory effect, detected only by a change in luminal pressure. 4 Al pha-chymotrypsin prevented the NT- and VIP-induced inhibitory effects and antagonized the response to EFS. 5 Apamin antagonized the EFS- and NT-induced effects, but failed to affect the relaxation in response t o exogenous VIP. 6 Desensitization of NT receptors by exposure to NT ( 10 nM) for 30 min did not affect the EFS-induced relaxation. 7 These f indings provide support for the involvement of a peptide in the NANC r elaxation in rat duodenum. However, there is no evidence that NT or VI P are neurotransmitters released from the NANC system in this preparat ion.