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-Ala⁸]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 (NK₂)-receptor antagonist MEN 10,627.

3. Under basal conditions SP, NKA, NKB, as well as the selective NK₁-receptor agonist SPME, the NK₂-receptor agonist [β-Ala⁸]NKA 4–10, and the NK₃-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-Ala⁸]NKA 4–10 but not to SP, SPME, NKA, NKB or senktide.

6. It is concluded that not only NK₂ receptors, but also other receptors, such as NK₁ and NK₃ receptors, may mediate the motility-stimulating action of different tachykinins in vivo.

7. It is further concluded that MEN 10,627 exerts a selective NK₂-receptor antagonism, and may be a valuable tool for assessing the functional role of NK₂-receptors in gastrointestinal physiology.

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