Scratching behavior induced by bombesin-related peptides. Comparison of bombesin, gastrin-releasing peptide and phyllolitorins

Masui, Akira; Kato, Nobuo; Itoshima, Takahiro; Tsunashima, Koichi; Nakajima, Terumi; Yanaihara, Noboru

doi:10.1016/0014-2999(93)90860-k

Cited by 28 publications

(18 citation statements)

References 18 publications

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“…Similar to previous studies (Masui et al, 1993;Sukhtankar and Ko, 2013), intrathecal GRP rapidly elicited scratching (Fig. 5).…”

Section: Roles Of Bnp-npra and Grp-grpr Systems In Itchsupporting

confidence: 89%

“…One of the central itch mediators is gastrinreleasing peptide (GRP), which acts as an enhancer of gastrin secretion from the gastric antrum through binding to its corresponding transmembrane GRP receptor (GRPR) (McDonald et al, 1979;Jensen et al, 2008). GRP has been used to elicit scratching responses in rodents (Bishop et al, 1986;Masui et al, 1993). With use of GRPR mutant mice, spinal GRP-GRPR signaling has been demonstrated to specifically regulate itch without altering pain thresholds (Sun and Chen, 2007).…”

Section: Introductionmentioning

confidence: 99%

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

Kiguchi

Sukhtankar

Ding

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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B-type natriuretic peptide (BNP)-natriuretic peptide receptor A (NPRA) and gastrin-releasing peptide (GRP)-GRP receptor (GRPR) systems contribute to spinal processing of itch. However, pharmacological and anatomic evidence of these two spinal ligandreceptor systems are still not clear. The aim of this study was to determine the spinal functions of BNP-NPRA and GRP-GRPR systems for regulating scratching activities in mice by using pharmacological and immunohistochemical approaches. Our results showed that intrathecal administration of BNP (0.3-3 nmol) dose dependently elicited scratching responses, which could be blocked by the NPRA antagonist (Arg6,b-cyclohexyl-Ala8,D-Tic16, Arg17,Cys18)-atrial natriuretic factor(6-18) amide (A71915). However, A71915 had no effect on intrathecal GRP-induced scratching. In contrast, pretreatment with a GRPR antagonist (D-Tpi6,Leu13c (CH2-NH)-Leu14)bombesin(6-14) (RC-3095) inhibited BNPinduced scratching. Immunostaining revealed that NPRA proteins colocalize with GRP, but not GRPR, in the superficial area of dorsal horn, whereas BNP proteins do not colocalize with either GRP or GRPR in the dorsal horn. Intradermal administration of ligands including endothelin-1, U-46619, bovine adrenal medulla 8-22, and Ser-Leu-Ile-Gly-Arg-Leu-NH 2 (SLIGRL) increased scratching bouts at different levels of magnitude. Pretreatment with intrathecal A71915 did not affect scratching responses elicited by all four pruritogens, whereas pretreatment with RC-3095 only inhibited SLIGRL-induced scratching. Interestingly, immunostaining showed that RC-3095, but not A71915, inhibited SLIGRLelicited c-Fos activation in the spinal dorsal horn, which was in line with behavioral outcomes. These findings demonstrate that: 1) BNP-NPRA system may function upstream of the GRP-GRPR system to regulate itch in the mouse spinal cord, and 2) both NPRA and GRPR antagonists may have antipruritic efficacy against centrally, but not peripherally, elicited itch.

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“…Similar to previous studies (Masui et al, 1993;Sukhtankar and Ko, 2013), intrathecal GRP rapidly elicited scratching (Fig. 5).…”

Section: Roles Of Bnp-npra and Grp-grpr Systems In Itchsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

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

Kiguchi

Sukhtankar

Ding

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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“…23,24 However, no change in these behaviors was observed in our previous studies. [10][11][12][13][14][15][16] Here, we also assessed grooming as well as other behaviors using ethological indices.…”

contrasting

confidence: 58%

Role of bombesin (BN)-like peptides/receptors in emotional behavior by comparison of three strains of BN-like peptide receptor knockout mice

et al. 2002

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Keywords: gastrin-releasing peptide receptor (GRP-R); bombesin receptor subtype-3 (BRS-3); neuromedin B receptor (NMB-R); light-dark (L-D) box test; elevated plus maze test; anxiety; emotion; knockout mice Bombesin (BN)-like peptides are involved in the regulation of a wide variety of behaviors, such as spontaneous activity and feeding. We assessed the role of BN-like peptides/receptors in emotional and/or anxietyrelated behavior using three strains of knockout mice, each deficient in a single BN-like peptide receptor (gastrin-releasing peptide receptor, bombesin receptor subtype-3, or neuromedin B receptor). Two representative behavioral paradigms, the light-dark (L-D) box test and the elevated plus maze test, were chosen for this purpose. In these two tests, the level of anxiety can be measured as the preference for exploring the light box, or the length of time spent in the open arms, respectively. By conventional parameters, the only significant finding was that BRS-3-deficient mice exhibited a longer duration of remaining in the open arms compared to the wild-type cohort (P Ͻ 0.01). However, analyses of risk assessment behavior revealed that BRS-3-deficient mice exhibited increased 'stretched attend posture' behavior (P Ͻ 0.01, compared to wild-type mice in both the L-D box and elevated plus maze tests) while NMB-Rdeficient mice exhibited decreased behavior (P Ͻ 0.05, compared to wild-type mice in both tests). These results suggest that BN-like peptides/receptors may play a role in modulating emotion including some forms of anxiety (eg, risk assessment behavior). Further, we found that the type of emotional behavior to which each of the peptide/receptor pathways contributes can be clearly specified. Molecular Psychiatry (2002) 7, 113-117. DOI: 10.1038/ sj/mp/4000974 Bombesin (BN) was originally purified from the skin of the European frog (Bombina bombina), 1 while the BNlike peptides gastrin-releasing peptide (GRP) and neuromedin B (NMB) were purified from mammalian tissues.2,3 These peptides exert their effects by binding to G-protein coupled receptors such as the GRP receptor (GRP-R), the NMB receptor (NMB-R), and the BN receptor subtype-3 (BRS-3) for which no specific endogenous ligand(s) has yet been identified. 4,5 BN-like peptides and their receptors are widely distributed in the mammalian CNS and modulate many aspects of behavior such as spontaneous activity and feeding behavior, as well as learning and memory. 6-9 We previously produced three strains of BN-like peptide receptor knockout mice using a gene targeting strategy. The resulting GRP-R-, NMB-R-and BRS-3-deficient mice were used in studies designed to clarify and distinguish the functional properties of BN-like peptides. These knockout mice exhibit unique phenotypes, such as elevated spontaneous activity and non-aggressive social behaviors in GRP-R-deficient mice.10-12 BRS-3-deficient mice exhibit moderate hyperphagia and obesity, 13 altered taste-related behaviors, 14 and decreased social behavior. 15 However, no behavioral phenotype has yet...

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“…There are few studies characterizing the scratching-eliciting effects of bombesin-related peptides. One early study (Masui et al, 1993) showed a similar plateau effect for intracerebroventricular GRP-elicited scratching within the dose range of 0.3 and 10 g in rats. In addition, by testing the same dose, intracerebroventricular administration of 1 g of bombesinrelated peptides all elicited scratching responses, but the degrees of scratching activities varied across different peptides (Masui et al, 1993).…”

Section: Discussionmentioning

confidence: 75%

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

Ko²

2011

J Pharmacol Exp Ther

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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.

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Scratching behavior induced by bombesin-related peptides. Comparison of bombesin, gastrin-releasing peptide and phyllolitorins

Cited by 28 publications

References 18 publications

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

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

Role of bombesin (BN)-like peptides/receptors in emotional behavior by comparison of three strains of BN-like peptide receptor knockout mice

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

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