Challa Siva Reddy, Levingston Hunter, Fornal Casimir A, Baker Isidra M, Boston Joseph, Shanthappa Nidhi, Unnam Pavani, Klopfenstein Jeffrey D, Veeravalli Krishna Kumar
Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine Peoria, Peoria, IL 61605, USA.
Department of Neurosurgery, University of Illinois College of Medicine Peoria, Peoria, IL 61605, USA.
Int J Mol Sci. 2025 Mar 7;26(6):2379. doi: 10.3390/ijms26062379.
Purinergic P2 receptors are crucial in energy utilization and cellular signaling, making them key targets for stroke therapies. This study examines the temporal mRNA expression of all P2 receptors in rats and mice. Both species exhibited a common subset of P2X and P2Y receptors with elevated expression following cerebral ischemia and reperfusion (I/R), highlighting conserved mechanisms across these species. The receptors with upregulated expression in both species were P2X3, P2X4, P2X7, P2Y2, and P2Y6. While these similarities were observed, notable differences in receptor expression emerged between rats and mice. Rats exhibited a broader receptor profile, with five additional receptors (P2X1, P2Y1, P2Y12, P2Y13, and P2Y14) significantly upregulated compared to only two receptors (P2X2 and P2Y4) in mice, highlighting species-specific regulation of receptor expression distinct from the shared receptors. Following cerebral I/R, P2Y12 was the most upregulated receptor in rats, while P2Y2 was the most upregulated in mice. These findings reveal both conserved and species-specific changes in P2 receptor expression following cerebral I/R. Targeting purinergic receptors, particularly those conserved and upregulated in response to stroke, may represent a promising therapeutic approach.
嘌呤能P2受体在能量利用和细胞信号传导中至关重要，使其成为中风治疗的关键靶点。本研究检测了大鼠和小鼠中所有P2受体的mRNA表达时间。两种动物均表现出一组常见的P2X和P2Y受体，在脑缺血再灌注（I/R）后表达升高，突出了这些物种间保守的机制。在两种动物中表达上调的受体是P2X3、P2X4、P2X7、P2Y2和P2Y6。虽然观察到了这些相似性，但大鼠和小鼠之间在受体表达上出现了显著差异。大鼠表现出更广泛的受体谱，与小鼠中仅两种受体（P2X2和P2Y4）显著上调相比，另外五种受体（P2X1、P2Y1、P2Y12、P2Y13和P2Y14）显著上调，突出了与共享受体不同的受体表达的物种特异性调节。脑I/R后，P2Y12是大鼠中上调最明显的受体，而P2Y2是小鼠中上调最明显的受体。这些发现揭示了脑I/R后P2受体表达中保守和物种特异性的变化。靶向嘌呤能受体，特别是那些在中风后保守且上调的受体，可能是一种有前景的治疗方法。
