흰쥐의 삼차신경절에서 Transient receptor potential ankyrin 1 (TRPA1)의 발현 특성에 관한 연구
Characterization of Trigeminal Ganglion Neurons Expressing Transient Receptor Potential Ankyrin 1 (TRPA1) in the Rat
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Transient receptor potential ankyrin 1 (TRPA1)은 17C보다 낮은 유해한 온도 및 자극적인 화합물에 의해 활성화되며 통각을조절한다. 그러나 TRPA1에 의한 통각정보가 어떻게 처리되는지에 대한 정보는 많이 알려져 있지 않다. 본 연구에서는 흰쥐의삼차신경절에서 TRPA1을 발현하는 신경세포의 특성을 규명하기 위해서, 면역형광기법을 사용하여 TRPA1을 발현하는 신경세포에서 다른 통각수용기들에서 발현되며, 특징적인 기능을 수행하는 수용기인 transient receptor potential vanilloid 1 (TRPV1)와P2X3와의 발현양상을 조사하였다. TRPA1을 발현하는 신경세포에서 열감각수용기이며, 통각표지자인 TRPV1과의 공존을 조사해 본 결과, TRPA1 면역양성 신경세포 중에서 58.8% (328/558)가 TRPV1을 동시에 발현하였으며, 41.2% (230/558)가 TRPA1만 발현하고 TRPV1을 발현하지않았다. TRPA1을 발현하는 신경세포 중 TRPV1을 동시에 발현하는 신경세포는 대부분 작거나 중간크기였다. 또한 TRPA1과조직의 손상, 그리고 염증 시 분비되는 ATP와 결합하는 P2X3와의 공존을 조사해 본 결과, TRPA1 면역양성 신경세포 중에서26.1% (310/1186)의 신경세포에서 P2X3을 동시에 발현하였으며,73.9% (876/1186)의 신경세포에서 TRPA1만 발현하였다. TRPA1을 발현하는 신경세포 중 P2X3을 동시에 발현하는 신경세포는 대부분 작거나 중간크기였다. 이러한 결과는 TRPA1을 발현하는 신경세포가 TRPV1 또는P2X3를 동시에 발현함으로써 동일한 신경세포가 구강안면영역에서의 냉통각 및 열통각을 조절할 뿐 아니라, 냉통각 및 염증성동통을 동시에 전달하는 등 하나의 신경세포가 여러 가지 통각의 전달에 관여하는 것을 시사한다.
Abstract
Transient receptor potential ankyrin 1 (TRPA1), responding to noxious cold (‹17C) and pungent compounds, is implicated in nociception, but little is known about the coexpression of TRPA1 and other channels or receptors involved in the nociception in craniofacial regions. To address this issue, we characterized the TRPA1-immunopositive (+) neurons in the rat trigeminal ganglion (TG) and investigated their colocalization with other proteins known to be expressed in nociceptive neurons, such as transient receptor potential vanilloid (TRPV1) and P2X3 receptor, using light microscopic immunofluorescence labeling method with TRPA1 and TRPV1 or P2X3 antisera. The majority of TRPA1+ neurons costained for TRPV1 (TRPV1+/TRPA1+; 58.8%, 328/558) and 41.2% only expressed TRPA1 but not TRPV1. The TRPV1+/TRPA1+ neurons were small and medium sized. In addition, we investigated the colocalization of TRPA1 with P2X3, a nonselective cation channel activated by ATP that may be released in the extracellular space as a result of tissue damage and inflammation. Among all TRPA1+ TG neurons, 26.1% (310/1186) costained for P2X3, whereas 73.9% (876/1186) of TRPA1+ neurons did not coexpress P2X3. P2X3+/TRPA1+ neurons were predominantly small and medium sized. These results suggest that TRPA1+ neurons coexpressing TRPV1 or P2X3 are involved in specific roles in the transmission and processing of orofacial nociceptive information by noxious cold, heat, and inflammation.
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