硫胺單磷酸酶（TMPase,，又稱為耐氟酸性磷酸酶）是一個典型的小直徑背根神經(jīng)節(jié)神經(jīng)元的組織化學(xué)標(biāo)記物,。目前有關(guān)TMPase的分子結(jié)構(gòu)尚不清楚。
在10月9日的《神經(jīng)元》（Neuron）雜志上,，Zylka等人研究發(fā)現(xiàn)，TMPase與前列腺酸性磷酸酶（PAP）的跨膜型異構(gòu)體相同，不過人們對于PAP的分子結(jié)構(gòu)和生理功能也不清楚,。
Zylka小組的研究表明，敲除PAP基因的小鼠有正常的急性疼痛的敏感性,，而慢性炎癥和神經(jīng)性疼痛反應(yīng)的疼痛敏感性增強,。在疼痛-功能的相互關(guān)聯(lián)的研究中發(fā)現(xiàn)：椎管注射PAP蛋白有較強的鎮(zhèn)痛和抗痛覺過敏作用，這種作用可以延長阿片類鎮(zhèn)痛嗎啡的作用時間,。PAP通過作用外-5'-核苷酸酶來抑制疼痛,，具體來說，PAP可以去除外磷酸腺苷（AMP）的腺苷后激活脊髓中的A1腺苷受體,。
至此,，Zylka等闡明了PAP在嘌呤核苷酸代謝和疼痛之間的分子機制和生理功能，從而提出了一種新的應(yīng)用PAP治療慢性疼痛的方法,。（生物谷Bioon.com）
生物谷推薦原始出處：
Neuron,，Volume 60, Issue 1, 111-122, 9 October 2008，Mark J. Zylka, Pirkko Vihko
Prostatic Acid Phosphatase Is an Ectonucleotidase and Suppresses Pain by Generating Adenosine
Mark J. Zylka1,5,,,Nathaniel A. Sowa1,5,Bonnie Taylor-Blake1,Margaret A. Twomey1,Annakaisa Herrala2,Vootele Voikar3andPirkko Vihko2,4,
1 Department of Cell and Molecular Physiology, UNC Neuroscience Center, University of North Carolina, CB #7545, Chapel Hill, NC 27599, USA
2 Department of Biological and Environmental Sciences, Division of Biochemistry, P.O. Box 56, FI-00014, University of Helsinki, Finland
3 Neuroscience Center, P.O. Box 56, FI-00014, University of Helsinki, Finland
4 Biocenter Oulu and Research Center for Molecular Endocrinology, P.O. Box 5000, FI-90014, University of Oulu, Finland
Thiamine monophosphatase (TMPase, also known as fluoride-resistant acid phosphatase) is a classic histochemical marker of small-diameter dorsal root ganglia neurons. The molecular identity of TMPase is currently unknown. We found that TMPase is identical to the transmembrane isoform of prostatic acid phosphatase (PAP), an enzyme with unknown molecular and physiological functions. We then found that PAP knockout mice have normal acute pain sensitivity but enhanced sensitivity in chronic inflammatory and neuropathic pain models. In gain-of-function studies, intraspinal injection of PAP protein has potent antinociceptive, antihyperalgesic, and antiallodynic effects that last longer than the opioid analgesic morphine. PAP suppresses pain by functioning as an ecto-5-nucleotidase. Specifically, PAP dephosphorylates extracellular adenosine monophosphate (AMP) to adenosine and activates A1-adenosine receptors in dorsal spinal cord. Our studies reveal molecular and physiological functions for PAP in purine nucleotide metabolism and nociception and suggest a novel use for PAP in the treatment of chronic pain.
