Nociceptin and Fragments

Introduction

Nociceptin, a 17-amino acid neuropeptide, has been recently identified as the endogenous ligand of the opioid receptor-like 1 receptor. Nociceptin itself acts as a potent anti-analgesic, effectively counteracting the effect of pain-relievers. In addition, it can initiate its function to work on many brain activities such as pain and fear learning. It has been shown that nociceptin is widely distributed in the central nervous system and it is found in the hypothalamus, brainstem, and forebrain, as well as the ventral and dorsal horns of the spinal cord. That’s to say, nociception and its receptors may involve a wide range of functions including learning, memory, attention, and emotion based on their distribution in the brain and spinal cord.

Nociceptin Fragments

The nociceptin N-terminal fragments (1–11) and (1–13) have a potency higher active than nociception, respectively. For example, nociceptin fragment (1–11) is approximately 2.0-fold more potent than naturally occurring peptide nociception. In addition, nociceptin (1-11) and (1-13) may involve distinct mechanisms at the level of the peripheral nerve terminal. However, the nociception fragment (1-7) had no effect on capsaicin-induced nociception. What’s more, nociceptin and the N-terminal fragment (1-13) also possess a function of local peripheral antinociceptive.

Mechanism of action

Nociceptin is a neuropeptide that has a suppression effect on synaptic transmission in the nervous system. In addition, nociception can initiate its function to act on many brain activities such as fear learning and pain sensation. It can effectively fight analgesic and effectively counteract the effects of painkillers. Nociceptin is a peptide associated with the opioid class of compounds, but it does not act at the typical opioid receptors and usually acts to relieve pain.

Application of Nociceptin and Fragments

Nociceptin has an inhibitory effect on synaptic transmission in the nervous system and involves learning, memory, attention, and mood, and also involves the perception of pain and visual, auditory and olfactory functions. In addition, nociceptin can also lend to activation of mitogen-activated protein kinases, activation of potassium channels and inhibition of adenylate cyclase, inhibition of calcium channels mobilization of intracellular calcium. At the same time, it acts as a potent anti-analgesic, effectively counteracting the effect of pain-relievers.

References

1. Calo', G., Guerrini, R., Rizzi, A., Salvadori, S., & Regoli, D. (2000). Pharmacology of nociceptin and its receptor: a novel therapeutic target. British journal of pharmacology, 129(7), 1261-1283.
2. Orsini, M. J., Nesmelova, I., Young, H. C., Hargittai, B., Beavers, M. P., Liu, J., ... & Mayo, K. H. (2005). The nociceptin pharmacophore site for opioid receptor binding derived from the NMR structure and bioactivity relationships. Journal of Biological Chemistry, 280(9), 8134-8142.