Mediation of irregular spiking activity by multiple neurokinin-receptors in the small intestine of the rat

Abstract

1. We have studied the small intestinal myoelectric response to the natural tachykinins substance P (SP), neurokinin A (NKA), neurokinin B (NKB), and the neurokinin-receptor selective agonists substance P methyl esther (SPME), [β-Ala(8)]neurokinin A 4-10, and senktide in conscious rats. 2. The effects of the agonists were studied before and after administration of the selective neurokinin (2) (NK(2))-receptor antagonist MEN 10,627. 3. Under basal conditions SP, NKA, NKB, as well as the selective NK(1)-receptor agonist SPME, the NK(2)-receptor agonist [β-Ala(8)]NKA 4–10, and the NK(3)-receptor agonist senktide, disrupted the interdigestive rhythm with regularly recycling migrating myoelectric complexes 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 [β-Ala(8)]NKA 4–10 but not to SP, SPME, NKA, NKB or senktide. 6. It is concluded that not only NK(2) receptors, but also other receptors, such as NK(1) and NK(3) receptors, may mediate the motility-stimulating action of different tachykinins in vivo. 7. It is further concluded that MEN 10,627 exerts a selective NK(2)-receptor antagonism, and may be a valuable tool for assessing the functional role of NK(2)-receptors in gastrointestinal physiology