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

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 P2X 1–7 and P2Y 1–14 receptors; however, the pres...

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Published in:Naunyn-Schmiedeberg's archives of pharmacology 2009-06, Vol.379 (6), p.541-549
Main Authors: Musa, Hanny, Tellez, James O., Chandler, Natalie J., Greener, Ian D., Mączewski, Michał, Mackiewicz, Urszula, Beresewicz, Andrzej, Molenaar, Peter, Boyett, Mark R., Dobrzynski, Halina
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cited_by cdi_FETCH-LOGICAL-c409t-2675bdd615a3d83c2bb1d2643333c0f9c3b6ac417f35d827790c9db14a19d9f83
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container_title Naunyn-Schmiedeberg's archives of pharmacology
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creator Musa, Hanny
Tellez, James O.
Chandler, Natalie J.
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Molenaar, Peter
Boyett, Mark R.
Dobrzynski, Halina
description 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 P2X 1–7 and P2Y 1–14 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. P2X 5 was the most abundant of the P2X receptors in all three regions of the rat heart. In rat left ventricle, P2Y 1 , P2Y 2 , and P2Y 14 mRNA levels were highest for P2Y receptors, while in right atrium and SAN, P2Y 2 and P2Y 14 levels were highest, respectively. We extended these studies to investigate P2X 4 receptor mRNA in heart from rats with coronary artery ligation-induced heart failure. P2X 4 receptor mRNA was upregulated by 93% in SAN ( P  
doi_str_mv 10.1007/s00210-009-0403-2
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Additionally, ATP is released from ischemic and hypoxic myocytes. Therefore, cardiac-derived sources of ATP have the potential to modify cardiac function. ATP activates P2X 1–7 and P2Y 1–14 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. P2X 5 was the most abundant of the P2X receptors in all three regions of the rat heart. In rat left ventricle, P2Y 1 , P2Y 2 , and P2Y 14 mRNA levels were highest for P2Y receptors, while in right atrium and SAN, P2Y 2 and P2Y 14 levels were highest, respectively. We extended these studies to investigate P2X 4 receptor mRNA in heart from rats with coronary artery ligation-induced heart failure. P2X 4 receptor mRNA was upregulated by 93% in SAN ( P  &lt; 0.05), while a trend towards an increase was also observed in the right atrium and left ventricle (not significant). Thus, P2X 4 -mediated effects might be modulated in heart failure. mRNA for P2X 4–7 and P2Y 1,2,4,6,12–14 , but not P2X 2,3 and P2Y 11 , was detected in human right atrium and SAN. In addition, mRNA for P2X 1 was detected in human SAN but not human right atrium. In human right atrium and SAN, P2X 4 and P2X 7 mRNA was the highest for P2X receptors. P2Y 1 and P2Y 2 mRNA were the most abundant for P2Y receptors in the right atrium, while P2Y 1 , P2Y 2 , and P2Y 14 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. 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Additionally, ATP is released from ischemic and hypoxic myocytes. Therefore, cardiac-derived sources of ATP have the potential to modify cardiac function. ATP activates P2X 1–7 and P2Y 1–14 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. P2X 5 was the most abundant of the P2X receptors in all three regions of the rat heart. In rat left ventricle, P2Y 1 , P2Y 2 , and P2Y 14 mRNA levels were highest for P2Y receptors, while in right atrium and SAN, P2Y 2 and P2Y 14 levels were highest, respectively. We extended these studies to investigate P2X 4 receptor mRNA in heart from rats with coronary artery ligation-induced heart failure. P2X 4 receptor mRNA was upregulated by 93% in SAN ( P  &lt; 0.05), while a trend towards an increase was also observed in the right atrium and left ventricle (not significant). Thus, P2X 4 -mediated effects might be modulated in heart failure. mRNA for P2X 4–7 and P2Y 1,2,4,6,12–14 , but not P2X 2,3 and P2Y 11 , was detected in human right atrium and SAN. In addition, mRNA for P2X 1 was detected in human SAN but not human right atrium. In human right atrium and SAN, P2X 4 and P2X 7 mRNA was the highest for P2X receptors. P2Y 1 and P2Y 2 mRNA were the most abundant for P2Y receptors in the right atrium, while P2Y 1 , P2Y 2 , and P2Y 14 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.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>19234689</pmid><doi>10.1007/s00210-009-0403-2</doi><tpages>9</tpages></addata></record>
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ispartof Naunyn-Schmiedeberg's archives of pharmacology, 2009-06, Vol.379 (6), p.541-549
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1432-1912
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source Springer Nature
subjects Adult
Animals
Biomedical and Life Sciences
Biomedicine
Female
Humans
Male
Middle Aged
Myocardium - chemistry
Myocardium - metabolism
Neurosciences
Original Aricle
Pharmacology/Toxicology
Rats
Rats, Wistar
Receptors, Purinergic P2 - analysis
Receptors, Purinergic P2 - metabolism
RNA, Messenger - analysis
RNA, Messenger - metabolism
Sinoatrial Node - chemistry
Sinoatrial Node - metabolism
title P2 purinergic receptor mRNA in rat and human sinoatrial node and other heart regions
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