HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Beneficial effect of chronic treatment with the selective bradykinin B1 receptor antagonists, R-715 and R-954, in attenuating streptozotocin-diabetic thermal hyperalgesia in mice.

Abstract
Kinins are important mediators of cardiovascular homeostasis, inflammation and nociception. Bradykinin (BK) B(1) receptors (BKB1-R) are over-expressed in pathological conditions including diabetes, and were reported to play a role in hyperglycemia, renal abnormalities, and altered vascular permeability associated with type 1 diabetes. Recent studies from our laboratory demonstrated that BKB1-R are implicated in streptozotocin (STZ)-diabetes-mediated hyperalgesia, since acute administration of the selective BKB1-R antagonists significantly and dose-dependently inhibited such hyperalgesic activity. In the present study, we examined the effect of chronic treatment of STZ-diabetic mice with the selective BKB1-R agonist desArg9bradykinin (DBK) and two specific antagonists R-715 and R-954, on diabetic hyperalgesia. Diabetes was induced in male CD-1 mice by injecting a single high dose of STZ (200mg/kg, i.p.) and nociception was assessed using the hot plate, plantar stimulation, tail immersion and tail flick tests. Drugs were injected i.p. twice daily for 7 days, starting 4 days after STZ. We showed that chronically administered R-715 (400 micrograms/kg) and R-954 (200 micrograms/kg), significantly attenuated the hyperalgesic effect developed in STZ-diabetic mice as measured by the four thermal nociceptive tests. Further, chronic treatment with DBK (400 micrograms/kg) produced a marked potentiation of the hyperalgesic activity, an effect that was reversed by both R-715 and R-954. The results from this chronic study confirm a pivotal role of the BKB1-R in the development of STZ-diabetic hyperalgesia and suggest a novel approach to the treatment of this short-term diabetic complication using BKB1-R antagonists.
AuthorsBichoy H Gabra, Pierre Sirois
JournalPeptides (Peptides) Vol. 24 Issue 8 Pg. 1131-9 (Aug 2003) ISSN: 0196-9781 [Print] United States
PMID14612183 (Publication Type: Journal Article)
Chemical References
  • Ac-Orn-(Oic2, alpha-MePhe5, D-betaNal7, Ile8)desArg9-bradykinin
  • Bradykinin B1 Receptor Antagonists
  • R 715
  • Bradykinin
Topics
  • Animals
  • Bradykinin (analogs & derivatives, pharmacology)
  • Bradykinin B1 Receptor Antagonists
  • Diabetes Mellitus, Experimental (drug therapy)
  • Hyperalgesia (drug therapy)
  • Male
  • Mice

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: