کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10451012 918381 2011 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Metallopeptidase inhibition potentiates bradykinin-induced hyperalgesia
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Metallopeptidase inhibition potentiates bradykinin-induced hyperalgesia
چکیده انگلیسی
The neuropeptide bradykinin (BK) sensitizes nociceptor activation following its release in response to inflammatory injury. Thereafter, the bioactivity of bradykinin is controlled by the enzymatic activities of circulating peptidases. One such enzyme, the metalloendopeptidase EC3.4.24.15 (EP24.15), is co-expressed with bradykinin receptors in primary afferent neurons. In this study, using approaches encompassing pharmacology, biochemistry, cell biology, and behavioral animal models, we identified a crucial role for EP24.15 and the closely related EP24.16 in modulating bradykinin-mediated hyperalgesia. Pharmacological analyses indicated that EP24.15 and EP24.16 inhibition significantly enhances bradykinin type-2 receptor activation by bradykinin in primary trigeminal ganglia cultures. In addition, bradykinin-induced sensitization of TRPV1 activation was increased in the presence of the EP24.15/16 inhibitor JA-2. Furthermore, behavioral analyses illustrated a significant dose-response relationship between JA-2 and bradykinin-mediated thermal hyperalgesia. These results indicate an important physiological role for the metallopeptidases EP24.15 and EP24.16 in regulating bradykinin-mediated sensitization of primary afferent nociceptors.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: PAIN® - Volume 152, Issue 7, July 2011, Pages 1548-1554
نویسندگان
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