Cheung Kwok Kuen, Coutinho-Silva Robson, Chan Wood Yee, Burnstock Geoffrey
Autonomic Neuroscience Centre, Royal Free and University College Medical School, London, United Kingdom.
Pancreas. 2007 Aug;35(2):164-8. doi: 10.1097/MPA.0b013e318053e00d.
Extracellular adenosine 5'-triphosphate modulates the functions of the adult pancreas via 2 nucleotide receptor families, the P2X and P2Y receptors. Expression of the P2X7 receptor has been demonstrated in islet cells of the pancreas, particularly the mature alpha cells that secrete glucagon. In the streptozotocin-induced diabetic model, a loss of insulin-secreting cells was accompanied by an increase in alpha cells that expressed the P2X7 receptor.
In the present study, we have examined the expression of P2X7 receptors in the developing pancreas from embryonic days 10 (E10) to E18.
We detected P2X7 receptor-immunoreactive cells in pancreatic islet cells as early as E11' before glucagon expression. Subsequently, P2X7 receptors were expressed in glucagon-secreting cells at E12, and complete colocalization was observed at E14. Occasional colocalization of P2X7 receptors and insulin was observed in scattered cells at E12 and E14, but not at E18, when the glucagon- and insulin-secreting cells were almost completely segregated.
It was found that P2X7 receptors were expressed early in a subpopulation of glucagon- and insulin-immunopositive cells in developing islets and subsequently became restricted to glucagon-expressing cells as development proceeded. The possible functional significance of these changes is discussed.
细胞外三磷酸腺苷(ATP)通过P2X和P2Y这两个核苷酸受体家族调节成年胰腺的功能。P2X7受体已在胰腺胰岛细胞中得到证实,尤其是在分泌胰高血糖素的成熟α细胞中。在链脲佐菌素诱导的糖尿病模型中,胰岛素分泌细胞的丧失伴随着表达P2X7受体的α细胞的增加。
在本研究中,我们检测了胚胎第10天(E10)至E18天发育中的胰腺中P2X7受体的表达。
早在胰高血糖素表达之前的E11,我们就在胰岛细胞中检测到了P2X7受体免疫反应性细胞。随后,P2X7受体在E12时在分泌胰高血糖素的细胞中表达,并在E14时观察到完全共定位。在E12和E14时,在散在细胞中偶尔观察到P2X7受体与胰岛素的共定位,但在E18时未观察到,此时分泌胰高血糖素和胰岛素的细胞几乎完全分离。
研究发现,P2X7受体在发育中的胰岛中胰高血糖素和胰岛素免疫阳性细胞亚群中早期表达,随后随着发育进程局限于表达胰高血糖素的细胞。讨论了这些变化可能的功能意义。