HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Potent neuropeptide Y Y1 receptor antagonist, 1229U91: blockade of neuropeptide Y-induced and physiological food intake.

Abstract
Neuropeptide Y (NPY) is thought to increase food intake through the action of Y1 (-like) receptors in the hypothalamus. To confirm the involvement of Y1 receptors in feeding behavior, selective and potent antagonists for Y1 receptors are required. In the present study, we showed that a peptide, 1229U91 [(Ile,Glu,Pro,Dpr,Tyr,Arg,Leu,Arg, Tyr-NH2)2 cyclic (2,4'),(2',4)-diamide], is a potent and selective antagonist for Y1 receptors. 1229U91 displaced [125I]peptide YY (PYY) binding to membranes of human neuroblastoma-derived SK-N-MC cells that predominantly express Y1 receptors with a K1 value 0.10 nM and inhibited the NPY-induced increase in intracellular calcium levels(IC50 = 0.27 nM). In contrast, the K1 values for [125I]PYY binding to Y2 receptors in membranes of human neuroblastoma-derived SK-N-BE2 cells and rat hypothalamus were 700 nM and more than 1 microM, respectively. Although [125I]PYY could not detect Y1 receptors in the rat hypothalamic membranes, [125I]1229U91 revealed binding sites with a high affinity (Kd = 18 pM), indicating the presence of Y1 receptors in the hypothalamus. Intracerebroventricular injection of 1229U91 (30 micrograms) into male Sprague-Dawley rats completely inhibited NPY (5 micrograms)-induced food intake without any other behavioral change. Furthermore, intracerebroventricular injection of 1229U91 significantly suppressed physiological feeding behavior after overnight fasting. These results indicate that Y1 receptors in the rat hypothalamus mediate NPY-induced food intake, and that physiological feeding behavior after overnight fasting may be largely regulated by NPY via Y1 receptors. 1229U91 may be useful for further elucidating the pathophysiological roles of NPY in feeding behavior.
AuthorsA Kanatani, A Ishihara, S Asahi, T Tanaka, S Ozaki, M Ihara
JournalEndocrinology (Endocrinology) Vol. 137 Issue 8 Pg. 3177-82 (Aug 1996) ISSN: 0013-7227 [Print] United States
PMID8754736 (Publication Type: Journal Article)
Chemical References
  • 1229U91
  • Neuropeptide Y
  • Peptides, Cyclic
  • Receptors, Gastrointestinal Hormone
  • peptide YY receptor
Topics
  • Animals
  • Dose-Response Relationship, Drug
  • Feeding Behavior (drug effects)
  • Humans
  • Hypothalamus (metabolism)
  • Male
  • Neuropeptide Y (pharmacology)
  • Peptides, Cyclic (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Gastrointestinal Hormone (antagonists & inhibitors)
  • Tumor Cells, Cultured

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: