Effects of endokinin A/B, endokinin C/D, and endomorphin-1 on the regulation of mean arterial blood pressure in rats.
Endokinins are four novel human tachykinins, including endokinins A (EKA), B (EKB), C (EKC), and D (EKD). Endokinin A/B (EKA/B) is the common C-terminal decapeptide in EKA and EKB, while endokinin C/D (EKC/D) is the common C-terminal duodecapeptide in EKC and EKD. In this study, we attempted to investigate the interactions between EKA/B, EKC/D, and endomorphin-1 (EM-1) on the depressor effect at peripheral level. The effects of EKA/B produced a U-shaped curve. The maximal effect was caused by 10 nmol/kg. EKC/D and EM-1 showed a dose-dependent relationship. Co-administration of EKA/B (0.1, 1, 10 nmol/kg) with EM-1 produced effects similar to those of EKA/B alone but slightly lower. Co-injection of EKA/B (100 nmol/kg) with EM-1 caused an effect stronger than any separate injection. Co-administration of EKC/D (10 nmol/kg) with EM-1 (30 nmol/kg) caused a depressor effect, which was one of the tradeoffs of EM-1 and EKC/D. Mechanism studies showed that SR140333B could block the depressor effects of EKA/B, EKC/D, EM-1, EKA/B+EM-1, and EKC/D+EM-1; SR48968C could block EM-1, EKA/B, EKC/D, and EKC/D+EM-1 and partially block EKA/B+EM-1; SR142801 could block EM-1, EKC/D, and EKC/D+EM-1 and partially block EKA/B and EKA/B+EM-1; naloxone could block EM-1, EKC/D, and EKC/D+EM-1 and partially block EKA/B and EKA/B+EM-1. Pretreatment with NG-nitro-l-arginine methyl ester partially decreased depressor intensity and half-recovery time of EKA/B and EKC/D.
Institute of Biochemistry and Molecular Biology, School of Life Sciences.
Qiaoying
Q
Jin
Li
L
Lu
Yinliang
Y
Yang
Shouliang
S
Dong
D000700:Analgesics / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D009842:Oligopeptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D015320:Tachykinins / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D014326:Tropanes / Q000494:pharmacology
D000700:Analgesics; D000928:Antidepressive Agents; D001549:Benzamides; D004338:Drug Combinations; D064729:Neurokinin-1 Receptor Antagonists; D009842:Oligopeptides; D010446:Peptide Fragments; D010880:Piperidines; D018041:Receptors, Neurokinin-2; C526005:SR140333B; D015320:Tachykinins; D014326:Tropanes; C105293:endomorphin 1; D009270:Naloxone; C073839:SR 48968; D019331:NG-Nitroarginine Methyl Ester