MEDIATION OF IRREGULAR SPIKING ACTIVITY BY MULTIPLE NEUROKININ-RECEPTORS IN THE SMALL-INTESTINE OF THE RAT

1 We have studied the small intestinal myoelectric response to the nat ural tachykinins substance P (SP), neurokinin A (NKA), neurokinin B (N KB), and the neurokinin-receptor selective agonists substance P methyl esther (SPME), [beta-Ala(8)]neurokinin A 4-10, and senktide in consci ous rats. 2 The effects of the agonists were studied before and after administration of the selective neurokinin(2) (NK2)-receptor antagonis t MEN 10,627. 3 Under basal conditions SP, NKA, NKB, as well as the se lective NK1-receptor agonist SPME, the NK2-receptor agonist [beta-Ala( 8)]NKA 4-10, and the NK3-receptor agonist senktide, disrupted the inte rdigestive rhythm with regularly recycling migrating myoelectric compl exes and induced a phase II-like irregular spiking activity. 4 MEN 10, 627 given alone did not affect the interdigestive rhythm. 5 MEN 10,627 inhibited the response to [beta-Ala(8)]NKA 4-10 but not to SP, SPME, NKA, NKB or senktide. 6 It is concluded that not only NK2 receptors, b ut also other receptors, such as NK1 and NK3 receptors, may mediate th e motility-stimulating action of different tachykinins in vivo. 7 It i s further concluded that MEN 10,627 exerts a selective NK2-receptor an tagonism, and may be a valuable tool for assessing the functional role of NK2-receptors in gastrointestinal physiology.