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.

► The dose–response curve of EKA/B is “U”-shaped.
► Co-injection of EKA/B with EM-1 or EKC/D shows a depressor effect similar to that of EKA/B alone.
► Co-injection of EKC/D and EM-1 causes a dose-dependent depressor effect.
► SR140333B, SR48968C, SR142801, naloxone, and l-NAME were used for mechanism studies.
► The depressor effect of EM-1 could be fully blocked not only by naloxone but also by SR140333B, SR48968C, and SR142801.