title: LVV-hemorphin 7 and angiotensin IV in correlation with antinociception and anti-thermal hyperalgesia in rats.
abstract: Hemorphins, a family of atypical endogenous opioid peptides, are produced by the cleavage of hemoglobin β-chain. Hemorphins were proved to bind to the μ-opioid receptors (agonist) and angiotensin IV receptors (insulin-regulated aminopeptidase; IRAP) (inhibitor). Among the hemorphins, LVV-hemorphin-7 (LVV-H7) was found to be abundant and with a longer half life in the CNS. Using intrathecal and intracerebroventricular injections, LVV-H7 and angiotensin IV were given to the rats, which were then subjected to the plantar test and the tail-flick test. Our results showed that LVV-H7 attenuated carrageenan-induced hyperalgesia at the spinal level, which could not be reversed by the co-administration of naloxone. At the supraspinal level, LVV-H7 also produced a significant anti-hyperalgesia effect but with a lower extent. Angiotensin IV showed a similar anti-hyperalgesia effect at the spinal level, but had no effect at the supraspinal level. In the tail-flick test and paw edema test, both peptides showed no effect. These results suggest that LVV-H7 mainly exert the anti-hyperalgesia effect at the spinal level, possibly through IRAP but not μ-opioid receptors. In addition, we observed the expression of IRAP in the CNS of animals with/without carrageenan-induced hyperalgesia. Our results showed a significant expression of IRAP in the spinal cord of rats. However, there was no significant quantitative change of IRAP after the development of hyperalgesia. The serum level of LVV-H7 was also found to be with no change caused by hyperalgesia. These results indicated that the endogenous LVV-H7 and IRAP may not regulate the severity of hyperalgesia through a quantitative change.
authors.affiliation: Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan, ROC.
authors.forename: Bor-Chih
authors.initials: BC
authors.lastname: Cheng
authors.forename: Pao-Luh
authors.initials: PL
authors.lastname: Tao
authors.forename: Ya-Yun
authors.initials: YY
authors.lastname: Cheng
authors.forename: Eagle Yi-Kung
authors.initials: EY
authors.lastname: Huang
mesh_terms: D000700:Analgesics / Q000008:administration & dosage*; D000804:Angiotensin II / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002351:Carrageenan; D010122:Cystinyl Aminopeptidase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004487:Edema / Q000188:drug therapy; D005528:Foot / Q000473:pathology; D006454:Hemoglobins / Q000008:administration & dosage*; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D009270:Naloxone / Q000008:administration & dosage; D059225:Nociception / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism
chemical_list: D000700:Analgesics; D006454:Hemoglobins; D010446:Peptide Fragments; D000804:Angiotensin II; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; D009270:Naloxone; C074309:LVV-hemorphin-7; D002351:Carrageenan; D010122:Cystinyl Aminopeptidase; C105964:leucyl-cystinyl aminopeptidase