Spasmolytic effect of the NK2-receptor-selective antagonist MEN 10,627 in rat small intestine.
The effect of activation of tachykinin NK2-receptors on gastrointestinal propulsion was studied in vivo in conscious rats. The selective NK2-receptor agonist [beta Ala8]NKA-(4-10) produced an atropine-resistant specific increase of the small intestinal transit measured by the charcoal method. This effect was restricted to the small intestine since gastric emptying was not affected by [beta Ala8]NKA-(4-10). The newly developed polycyclic peptide NK2-receptor antagonist MEN 10,627 produced a dose-dependent inhibition of this stimulated transit. The spasmolytic effect of MEN 10,627 was highly selective because it did not affect stimulated intestinal transit induced by equieffective doses of carbachol and reserpine. These findings indicate that MEN 10,627 is a valuable tool for assessing the role of NK2-receptors in intestinal propulsive activity.
Tramontana
M
M
Pharmacology Department, Istituto Farmacobiologico Malesci S.p.A., Firenze, Italy.
Maggi
C A
CA
Evangelista
S
S
D000595:Amino Acid Sequence; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005746:Gastric Emptying / Q000187:drug effects; D005772:Gastrointestinal Transit / Q000187:drug effects; D007275:Injections, Intravenous; D007421:Intestine, Small / Q000187:drug effects*; D008297:Male; D008969:Molecular Sequence Data; D015288:Neurokinin A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors*
D010446:Peptide Fragments; D010456:Peptides, Cyclic; D018041:Receptors, Neurokinin-2; C064218:neurokinin A (4-10), beta-Ala(8)-; C090951:MEN 10627; D015288:Neurokinin A; D002217:Carbachol