Filippi A, Caruntu C, Gheorghe R O, Deftu A, Amuzescu B, Ristoiu V
Department of Medical Biophysics, 'Carol Davila' University of Medicine and Pharmacy, Bucharest, Romania.
Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, Bucharest, Romania.
J Physiol Pharmacol. 2016 Dec;67(6):843-850.
Sympathetic nervous system and adrenergic receptors are involved in the modulation of dorsal root ganglia neuronal activity, with TRPV1 receptor as an important downstream effector. It is already known that adrenergic sensitization of TRPV1 receptors or catecholamine-induced TRPV1 upregulation are involved in increased excitability and pain via mainly α adrenergic receptors, but it is not known if reduced TRPV1 desensitization is involved in this process, as well. Therefore, the aims of this study were to evaluate the effects of epinephrine and norepinephrine on TRPV1 desensitization induced by repeated applications of capsaicin and to assess what would be the involvement of the major α, α and β adrenergic receptor subtypes. Using calcium microfluorimetry, the effects were evaluated by exposure to 1 μM epinephrine or 10 μM norepinephrine, alone or in the presence of adrenergic receptor inhibitors (phentolamine, prazosin and propranolol) before a 4 capsaicin application in a series of 5 consecutive capsaicin applications. The results showed that both catecholamines produced significant reduction of TRPV1 desensitization, which was mediated by α, α and β receptors. This study completes the general information about TRPV1 sensitization via adrenergic stimulation and may open perspectives for novel pharmacological approaches in skin inflammatory disorders and pain therapy.
交感神经系统和肾上腺素能受体参与背根神经节神经元活动的调节,其中TRPV1受体是重要的下游效应器。已知TRPV1受体的肾上腺素能致敏或儿茶酚胺诱导的TRPV1上调主要通过α肾上腺素能受体参与兴奋性增加和疼痛,但尚不清楚TRPV1脱敏降低是否也参与此过程。因此,本研究的目的是评估肾上腺素和去甲肾上腺素对辣椒素重复应用诱导的TRPV1脱敏的影响,并评估主要的α、α和β肾上腺素能受体亚型的参与情况。使用钙微荧光法,在连续5次应用辣椒素的系列中,在应用4次辣椒素之前,单独或在存在肾上腺素能受体抑制剂(酚妥拉明、哌唑嗪和普萘洛尔)的情况下,通过暴露于1μM肾上腺素或10μM去甲肾上腺素来评估其效果。结果表明,两种儿茶酚胺均显著降低了TRPV1脱敏,这是由α、α和β受体介导的。本研究完善了通过肾上腺素能刺激使TRPV1致敏的一般信息,并可能为皮肤炎症性疾病和疼痛治疗的新药理学方法开辟前景。