P2 purinergic receptor mRNA in rat and human sinoatrial node and other heart regions

Musa, Hanny, Tellez, James O., Chandler, Natalie J., Greener, Ian D., Maczewski, Michał, Mackiewicz, Urszula, Beresewicz, Andrzej, Molenaar, Peter, Boyett, Mark R. and Dobrzynski, Halina (2009) P2 purinergic receptor mRNA in rat and human sinoatrial node and other heart regions. Naunyn-Schmiedeberg's Archives of Pharmacology, 379 6: 541-549. doi:10.1007/s00210-009-0403-2


Author Musa, Hanny
Tellez, James O.
Chandler, Natalie J.
Greener, Ian D.
Maczewski, Michał
Mackiewicz, Urszula
Beresewicz, Andrzej
Molenaar, Peter
Boyett, Mark R.
Dobrzynski, Halina
Title P2 purinergic receptor mRNA in rat and human sinoatrial node and other heart regions
Journal name Naunyn-Schmiedeberg's Archives of Pharmacology   Check publisher's open access policy
ISSN 0028-1298
1432-1912
Publication date 2009-06
Sub-type Article (original research)
DOI 10.1007/s00210-009-0403-2
Volume 379
Issue 6
Start page 541
End page 549
Total pages 10
Place of publication Heidelberg, Germany
Publisher Springer
Language eng
Subject 300512 Pharmacology
11 Medical and Health Sciences
Formatted abstract
It is known that adenosine 5′-triphosphate (ATP) is a cotransmitter in the heart. Additionally, ATP is released from ischemic and hypoxic myocytes. Therefore, cardiac-derived sources of ATP have the potential to modify cardiac function. ATP activates P2X1–7 and P2Y1–14 receptors; however, the presence of P2X and P2Y receptor subtypes in strategic cardiac locations such as the sinoatrial node has not been determined. An understanding of P2X and P2Y receptor localization would facilitate investigation of purine receptor function in the heart. Therefore, we used quantitative PCR and in situ hybridization to measure the expression of mRNA of all known purine receptors in rat left ventricle, right atrium and sinoatrial node (SAN), and human right atrium and SAN. Expression of mRNA for all the cloned P2 receptors was observed in the ventricles, atria, and SAN of the rat. However, their abundance varied in different regions of the heart. P2X5 was the most abundant of the P2X receptors in all three regions of the rat heart. In rat left ventricle, P2Y1, P2Y2, and P2Y14 mRNA levels were highest for P2Y receptors, while in right atrium and SAN, P2Y2 and P2Y14 levels were highest, respectively. We extended these studies to investigate P2X4 receptor mRNA in heart from rats with coronary artery ligation-induced heart failure. P2X4 receptor mRNA was upregulated by 93% in SAN (P < 0.05), while a trend towards an increase was also observed in the right atrium and left ventricle (not significant). Thus, P2X4-mediated effects might be modulated in heart failure. mRNA for P2X4–7 and P2Y1,2,4,6,12–14, but not P2X2,3 and P2Y11, was detected in human right atrium and SAN. In addition, mRNA for P2X1 was detected in human SAN but not human right atrium. In human right atrium and SAN, P2X4 and P2X7 mRNA was the highest for P2X receptors. P2Y1 and P2Y2 mRNA were the most abundant for P2Y receptors in the right atrium, while P2Y1, P2Y2, and P2Y14 were the most abundant P2Y receptor subtypes in human SAN. This study shows a widespread distribution of P2 receptor mRNA in rat heart tissues but a more restricted presence and distribution of P2 receptor mRNA in human atrium and SAN. This study provides further direction for the elucidation of P2 receptor modulation of heart rate and contractility.
Keyword P2 receptors
Human heart
Rat heart
Ventricles
Atria
Sinoatrial node
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 22 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 03 Sep 2009, 08:17:34 EST by Mr Andrew Martlew on behalf of Faculty Of Health Sciences