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Prolactin-releasing Peptide Family Related Drug Discovery Products

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Prolactin-releasing peptide (PrRP) belongs to the family of RFamide peptides. In animals, PrRP is not a typical hypothalamic releasing factor. However, prolactin and numerous other pituitary hormones, including adrenocorticotropic hormone (ACTH), oxytocin, vasopressin, and lutenizing hormone/follicle-stimulating hormone, are secreted when PrRP is administered intracerebroventricularly. Additionally, PrRP has been shown to be involved in analgesia, waking/sleeping states, stress responses, and energy metabolism.

Overview of PrRP system. Fig.1. Overview of PrRP system. (Onaka, 2010)

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Overview of Prolactin-releasing Peptide Family

The rat brain's various regions with the greatest GPR10 expression levels included the reticular nucleus of the thalamus (RT), PVN, periventricular hypothalamic nucleus (PEVN), as well as the DMN, AP, and NTS. In the anterior pituitary and VMN, the receptor was also shown to be expressed at a modest level. GPR10 was also detected at low levels in the hippocampus, which contains regions involved in memory, and in the parabrachial nucleus (PB) or nucleus accumbens (NAc), which are regions involved in processing pain.

In a calcium mobilization experiment, PrRP was able to dose-dependently promote calcium release in cells that were transfected with GPR10. Extracellular signal-regulated protein kinase (ERK) of the mitogen-activated protein kinase (MAPK) family was quickly activated by PrRP in primary rat anterior pituitary cultures and GH3 rat pituitary tumor cells. Further evidence that at least some of the coupling of GPR10 is through Gi/Go proteins comes from the fact that pertussis toxin (PTX), which inactivates Gi/Go proteins, entirely prevented the ERK activation produced by PrRP. In GH3 cells, PrRP quickly and transiently increased the activation of protein kinase B (Akt), which was inhibited by a phosphoinositide 3-kinase-protein kinase (PI3K) inhibitor. Additionally, PTX totally prevented the Akt activation brought on by PrRP, pointing to the participation of Gi/Go proteins.

PrRP physiological functions and signaling. Fig.2. PrRP physiological functions and signaling. (Pražienková, 2019)

Prolactin-releasing Peptide Family Drug Discovery

Given PrRP's significance for energy metabolism and stress responses, the PrRP-GPR10 system may be a useful therapeutic target for illnesses associated with obesity or chronic stress. An essential point of integration in the regulation of energy metabolism and stress responses is the PrRP system. The downstream mechanisms of the PrRP system and the precise roles of the hypothalamus and brainstem PrRP neurons are among the many unanswered topics. These issues will be addressed through the development of novel pharmaceutical techniques or new genetically modified animal models.

References

  1. Onaka, T.; et al. Metabolic and stress-related roles of prolactin-releasing peptide. Trends in Endocrinology & Metabolism. 2010, 21(5): 287-293.
  2. Pražienková, V.; et al. Prolactin-releasing peptide: physiological and pharmacological properties. International Journal of Molecular Sciences. 2019, 20(21): 5297.

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