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 natural tachykinins substance P (SP), neurokinin A (NKA), neurokinin B (NKB), and the neurokinin-receptor selective agonists substance P methyl esther (SPME), [beta-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 neurokinin2 (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 [beta-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 [beta-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.
Lördal
M
M
Department of Gastroenterology and Hepatology, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
Bränström
R
R
Hellström
P M
PM
D000818:Animals; D004576:Electromyography; D004594:Electrophysiology; D005769:Gastrointestinal Motility / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016065:Myoelectric Complex, Migrating / Q000187:drug effects; D015288:Neurokinin A / Q000494:pharmacology; D015287:Neurokinin B / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000819:agonists; D018041:Receptors, Neurokinin-2 / Q000819:agonists / Q000037:antagonists & inhibitors*; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology*
D010456:Peptides, Cyclic; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D015320:Tachykinins; C090951:MEN 10627; D013373:Substance P; D015288:Neurokinin A; D015287:Neurokinin B