Polypeptide modulators of TRPV1 produce analgesia without hyperthermia.
Polypeptide modulators of TRPV1 produce analgesia without hyperthermia.
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DOI：
10.3390/md11125100
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发表时间：
2013-12-16
期刊：
影响因子：
5.4
通讯作者：
Grishin EV
中科院分区：
文献类型：
--
作者：
Andreev YA;Kozlov SA;Korolkova YV;Dyachenko IA;Bondarenko DA;Skobtsov DI;Murashev AN;Kotova PD;Rogachevskaja OA;Kabanova NV;Kolesnikov SS;Grishin EV
瞬时受体电位香草素1受体(TRPV1)具有重要的生理作用。研究新型的TRPV1激动剂和拮抗剂是非常必要的。在此，我们报道了基于体外和体内实验的TRPV1多肽拮抗剂的特性。我们用全细胞膜片钳技术和单细胞钙成像技术评价了APHC1和APHC3抑制TRPV1的能力。通过体内实验评价APHC1和APHC3对体温、炎症和核心体温的生物学效应。在电生理研究中，两种多肽都部分阻断了辣椒素诱导的TRPV1的反应，但只有APHC3抑制了酸诱导的(pH 5.5)受体的激活。APHC1和APHC3在合理剂量(0.01-0.1 mg/kg)下具有明显的体内抗伤害性和镇痛活性，且不引起体温升高。静脉注射这些多肽延长了热板潜伏期，阻断了辣椒素和福尔马林诱导的行为，逆转了CFA诱导的痛敏，并产生了低温。值得注意的是，APHC3的S能够抑制低pH诱导的TRPV1的激活，导致在醋酸诱导的扭体实验中的行为反应减少，而APHC1的效果要差得多。多肽APHC1和APHC3可被称为一类新的TRPV1调节剂，在不加热的情况下具有显著的镇痛作用。
Transient receptor potential vanilloid 1 receptors (TRPV1) play a significant physiological role. The study of novel TRPV1 agonists and antagonists is essential. Here, we report on the characterization of polypeptide antagonists of TRPV1 based on in vitro and in vivo experiments. We evaluated the ability of APHC1 and APHC3 to inhibit TRPV1 using the whole-cell patch clamp approach and single cell Ca2+ imaging. In vivo tests were performed to assess the biological effects of APHC1 and APHC3 on temperature sensation, inflammation and core body temperature. In the electrophysiological study, both polypeptides partially blocked the capsaicin-induced response of TRPV1, but only APHC3 inhibited acid-induced (pH 5.5) activation of the receptor. APHC1 and APHC3 showed significant antinociceptive and analgesic activity in vivo at reasonable doses (0.01–0.1 mg/kg) and did not cause hyperthermia. Intravenous administration of these polypeptides prolonged hot-plate latency, blocked capsaicin- and formalin-induced behavior, reversed CFA-induced hyperalgesia and produced hypothermia. Notably, APHC3’s ability to inhibit the low pH-induced activation of TRPV1 resulted in a reduced behavioural response in the acetic acid-induced writhing test, whereas APHC1 was much less effective. The polypeptides APHC1 and APHC3 could be referred to as a new class of TRPV1 modulators that produce a significant analgesic effect without hyperthermia.
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影响因子：
6.1
作者：
Ikeda, Y;Ueno, A;Oh-ishi, S
通讯作者：
Oh-ishi, S
影响因子：
3
作者：
Kozlov, Sergey;Grishin, Eugene
通讯作者：
Grishin, Eugene
DOI：
10.1111/j.1432-1033.1993.tb17705.x
发表时间：
1993-03-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
ANTUCH, W;BERNDT, KD;WUTHRICH, K
通讯作者：
WUTHRICH, K
影响因子：
5.3
作者：
Gavva, Narender R.;Bannon, Anthony W.;Louis, Jean-Claude
通讯作者：
Louis, Jean-Claude
DOI：
10.1073/pnas.0705924104
发表时间：
2007-08-14
影响因子：
11.1
作者：
McNamara, Colleen R.;Mandel-Brehm, Josh;Fanger, Christopher M.
通讯作者：
Fanger, Christopher M.