The Role of Central Gastrin-Releasing Peptide and Neuromedin B Receptors in the Modulation of Scratching Behavior in Rats

Abstract

Bombesin is a pruritogenic agent that causes intense itchscratching activity in rodents. Bombesin has high affinity for the gastrin-releasing peptide (GRP) receptor (GRPr) and the neuromedin B (NMB) receptor (NMBr). The aim of this study was to investigate pharmacologically the ability of GRPr and NMBr to elicit scratching behavior in rats. The intracerebroventricular route was selected for drug delivery because the study focused on supraspinal sites of action. The magnitude and duration of scratching produced by the naturally occurring peptides GRP and NMB were characterized. and NMB (0.1-1 nmol) dose-dependently elicited marked scratching. There was a tolerance to scratching elicited by daily repeated administration of bombesin, GRP, or NMB. Presession administration of RC-3095 (0.1-1 nmol) and PD168368 (0.3-3 nmol) dosedependently antagonized scratching elicited by GRP and NMB, respectively. More importantly, 1 nmol of RC-3095 failed to block NMB-elicited scratching, and 3 nmol of PD168368 failed to block GRP-elicited scratching. In addition, pretreatment with effective doses of RC-3095 or PD168368 alone or in combination did not block bombesin-elicited scratching. Through the use of the selective antagonists RC-3095 and PD168368, this study demonstrates that central GRPr and NMBr act independently to elicit scratching behavior and there is an additional, unidentified receptor mechanism underlying bombesin-elicited scratching.

Spinal Functions of B-Type Natriuretic Peptide, Gastrin-Releasing Peptide, and Their Cognate Receptors for Regulating Itch in Mice

“…In addition, spinal blockade of GRPR is partially effective in regulating peripherally elicited itch. It is interesting to note that activation of supraspinal GRPR can also elicit excessive scratching in rodents (Su and Ko, 2011). Given that nonhuman primate behavioral models have been used to distinguish spinal versus supraspinal actions of different ligand-receptor systems for regulating itch and pain (Ding et al, 2015;Lee and Ko, 2015), it is essential to further investigate the functional relationship of central GRP-GRPR and BNP-NPRA systems in primates.…”

Potential New Therapeutic Targets for Pathological Pruritus

“…79) Neuromedin B is mainly expressed in small-sized sensory neurons. 72) Intracerebroventricular injections of neuromedin B (and of GRP) elicits scratching in rats, 80) but intrathecal injection of neuromedin B elicits pain-like behaviors. 81) Toll-like receptors mediate innate immune responses and recognize pathogen-associated molecule patterns.…”

Itch elicited by intradermal injection of serotonin, intracisternal injection of morphine, and their synergistic interactions in rats

“…In addition to pruritogens which cause itch via activation of peripheral nociceptors, there are a number of agents which cause itch-related behaviors when administered to the CNS in animal models (Koenigstein, 1948; Thomas and Hammond, 1995; Lee et al, 2003; Sun and Chen, 2007; Su and Ko, 2011; Mishra and Hoon, 2013). Morphine is one of the most frequently studied agents of this type.…”