Pain regulation of endokinin A/B or endokinin C/D on chimeric peptide MCRT in mice.
The present study focused on the interactive pain regulation of endokinin A/B (EKA/B, the common C-terminal decapeptide in EKA and EKB) or endokinin C/D (EKC/D, the common C-terminal duodecapeptide in EKC and EKD) on chimeric peptide MCRT (YPFPFRTic-NH2, based on YPFP-NH2 and PFRTic-NH2) at the supraspinal level in mice. Results demonstrated that the co-injection of nanomolar EKA/B and MCRT showed moderate regulation, whereas 30 pmol EKA/B had no effect on MCRT. The combination of EKC/D and MCRT produced enhanced antinociception, which was nearly equal to the sum of the mathematical values of single EKC/D and MCRT. Mechanism studies revealed that pre-injected naloxone attenuated the combination significantly compared with the equivalent analgesic effects of EKC/D alone, suggesting that EKC/D and MCRT might act on two totally independent pathways. Moreover, based on the above results and previous reports, we made two reasonable hypotheses to explain the cocktail-induced analgesia, which may potentially pave the way to explore the respective regulatory mechanisms of EKA/B, EKC/D, and MCRT and to better understand the complicated pain regulation of NK1 and μ opioid receptors, as follows: (1) MCRT and endomorphin-1 possibly activated different μ subtypes; and (2) picomolar EKA/B might motivate the endogenous NPFF system after NK1 activation.
a Institute of Biochemistry and Molecular Biology, School of Life Sciences, 222 Tianshui South Road, Lanzhou 730000, China.
Chunbo
C
He
a Institute of Biochemistry and Molecular Biology, School of Life Sciences, 222 Tianshui South Road, Lanzhou 730000, China.
Junbin
J
Gong
a Institute of Biochemistry and Molecular Biology, School of Life Sciences, 222 Tianshui South Road, Lanzhou 730000, China.
Lixia
L
Yang
a Institute of Biochemistry and Molecular Biology, School of Life Sciences, 222 Tianshui South Road, Lanzhou 730000, China.
Hongwei
H
Zhang
a Institute of Biochemistry and Molecular Biology, School of Life Sciences, 222 Tianshui South Road, Lanzhou 730000, China.|b Key Laboratory of Preclinical Study for New Drugs of Gansu Province, 222 Tianshui South Road, Lanzhou 730000, China.
Shouliang
S
Dong
c The Core Laboratory of the First Affiliated Hospital, Lanzhou University, 1 Donggang West Road, Lanzhou 730000, China.|d Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou 730000, China.
Lanxia
L
Zhou
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004723:Endorphins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D057967:Infusions, Intraventricular; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011498:Protein Precursors / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015320:Tachykinins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000700:Analgesics; D004723:Endorphins; C582447:MCRT peptide; D010446:Peptide Fragments; D011498:Protein Precursors; C423233:Tac4 protein, mouse; D015320:Tachykinins; D009270:Naloxone
MCRT; NK1 receptor; co-injection; endokinin A/B; endokinin C/D; endokinine A/B; endokinine C/D; opioid receptors; pain regulation; récepteur NK1; récepteurs d’opioïdes; régulation de la douleur