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

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. The effects of the agonists were studied before and after administration of the selective neurokinin 2 (NK 2 )‐receptor antagonist MEN 10,627. 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. MEN 10,627 given alone did not affect the interdigestive rhythm. MEN 10,627 inhibited the response to [β‐Ala 8 ]NKA 4–10 but not to SP, SPME, NKA, NKB or senktide. 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 . 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.British Journal of Pharmacology (1998) 123 , 63–70; doi: 10.1038/sj.bjp.0701585