Physiological function of gastrin-releasing peptide and neuromedin B receptors in regulating itch scratching behavior in the spinal cord of mice.
Physiological function of gastrin-releasing peptide and neuromedin B receptors in regulating itch scratching behavior in the spinal cord of mice.
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DOI：
10.1371/journal.pone.0067422
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ko MC
中科院分区：
文献类型：
--
作者：
Sukhtankar DD;Ko MC
瘙痒是一种与使用药物以及肝脏和血液系统疾病相关的严重副作用。以往对啮齿动物的研究表明，蛙皮素受体亚型，即胃泌素释放肽受体(GRPR)和神经介素B(NMBr)对瘙痒有不同的调节作用。然而，脊髓GRPR和NMBR在多大程度上调节鞘内注射蛙皮素相关多肽引起的抓挠尚不清楚。这项研究的第一个目的是从药理学上比较鞘内注射蛙皮素相关多肽和吗啡引起的瘙痒的剂量-反应曲线，吗啡是已知的引起人类瘙痒的药物。第二个目的是确定脊髓GRPR和NMBR是否选择性地或一般地调节抓挠行为。小鼠鞘内注射蛙皮素(0.01~0.3nmol)、GRP(0.01~0.3nmol)、NMB(0.1~1nmol)或吗啡(0.3~3nmol)，观察1小时后的抓挠活动。在1小时内，蛙皮素引起的抓挠最深，其次是GRP和NMB，而吗啡没有引起抓挠反应，这表明小鼠模型对鞘内阿片诱导的瘙痒不敏感。鞘内注射GRPR拮抗剂RC-3095(0.03-0.1nmol)可使GRP诱导的划痕反应曲线平行右移，但对NMB诱导的划痕反应无影响。类似地，PD168368(1-3nmol)仅减弱NMB，但不能减弱GRP引起的划痕。RC-3095和PD168368单独或联合应用均不能改变蛙皮素引起的划痕。较高剂量的RC-3095(0.3nmol)一般抑制这三种多肽引起的划痕，但在旋转棒试验中也损害运动功能。总之，这些数据表明，脊髓GRPR和NMBR独立地驱动小鼠的瘙痒神经传递，可能不介导蛙皮素诱导的抓挠。功能性受体选择性剂量的GRPR拮抗剂仅阻断脊髓GRP引起的抓挠，但在较高剂量下对抓挠的抑制被运动损伤所混淆。
Pruritus (itch) is a severe side effect associated with the use of drugs as well as hepatic and hematological disorders. Previous studies in rodents suggest that bombesin receptor subtypes i.e. receptors for gastrin-releasing peptide (GRPr) and neuromedin B (NMBr) differentially regulate itch scratching. However, to what degree spinal GRPr and NMBr regulate scratching evoked by intrathecally administered bombesin-related peptides is not known. The first aim of this study was to pharmacologically compare the dose-response curves for scratching induced by intrathecally administered bombesin-related peptides versus morphine, which is known to elicit itch in humans. The second aim was to determine if spinal GRPr and NMBr selectively or generally mediate scratching behavior. Mice received intrathecal injection of bombesin (0.01–0.3 nmol), GRP (0.01–0.3nmol), NMB (0.1–1nmol) or morphine (0.3–3 nmol) and were observed for one hour for scratching activity. Bombesin elicited most profound scratching over one hour followed by GRP and NMB, whereas morphine failed to evoke scratching response indicating the insensitivity of mouse models to intrathecal opioid-induced itch. Intrathecal pretreatment with GRPr antagonist RC-3095 (0.03–0.1 nmol) produced a parallel rightward shift in the dose response curve of GRP-induced scratching but not NMB-induced scratching. Similarly, PD168368 (1–3 nmol) only attenuated NMB but not GRP-induced scratching. Individual or co-administration of RC-3095 and PD168368 failed to alter bombesin-evoked scratching. A higher dose of RC-3095 (0.3 nmol) generally suppressed scratching induced by all three peptides but also compromised motor function in the rotarod test. Together, these data indicate that spinal GRPr and NMBr independently drive itch neurotransmission in mice and may not mediate bombesin-induced scratching. GRPr antagonists at functionally receptor-selective doses only block spinal GRP-elicited scratching but the suppression of scratching at higher doses is confounded by motor impairment.
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DOI：
10.1152/physiol.00007.2011
发表时间：
2011-08
期刊：
Physiology (Bethesda, Md.)
影响因子：
--
作者：
Jeffry J;Kim S;Chen ZF
通讯作者：
Chen ZF
影响因子：
2.9
作者：
Johnson, MD;Ko, MC;Woods, JH
通讯作者：
Woods, JH
DOI：
10.1111/j.1749-6632.1988.tb38614.x
发表时间：
1988-05-10
影响因子：
5.2
作者：
GMEREK, DE;COWAN, A
通讯作者：
COWAN, A
DOI：
10.1124/jpet.103.061101
发表时间：
2004-07-01
影响因子：
3.5
作者：
Ko, MCH;Song, MS;Naughton, NN
通讯作者：
Naughton, NN
影响因子：
8.8
作者：
Palmer, CM;Emerson, S;Alves, D
通讯作者：
Alves, D