Bradykinin induced sustained anti–adrenergic actions in guinea pig heart muscle involves PKC

Arvola, L.; Bertelsen, Geir; Ytrehus, Kirsti

doi:10.1080/14017430601187124

Cited by 1 publication

(2 citation statements)

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“…Bradykinin also competes with adrenergic stimulation of the heart. 16 Our rabbit cardiomyocytes have surprisingly high basal adenylyl cyclase activities, resulting in a futile cycling of cAMP synthesis and breakdown in these quiescent cells. This basal adenylyl cyclase activity is reflected in the rise in cAMP when the major PDEs were inhibited with the PDE inhibitor cocktail.…”

Section: Discussionmentioning

confidence: 99%

“…The cardiomyocyte hypothesis of preconditioning would be disproved if it could be shown that one or more of the receptors used by IPC's signaling are not expressed by the cardiomyocyte. Adenosine A 1 AR stimulation markedly inhibits isoproterenol (iso)-induced increase in contractility 15 as does bradykinin, 16 indicating that both of those receptors coexist with adrenergic receptors on cardiomyocytes. It has been more difficult to demonstrate the presence of the remaining receptors.…”

Section: Introductionmentioning

confidence: 99%

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All Preconditioning-Related G Protein-Coupled Receptors Can Be Demonstrated in the Rabbit Cardiomyocyte

Xin

Yang

Rich

et al. 2011

J Cardiovasc Pharmacol Ther

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G protein-coupled receptors for adenosine (A1, A3, A2A and A2B), bradykinin (B1) and opioids (δ) are all involved in the mechanism of ischemic preconditioning. Although the heart is comprised of many tissue types it has been assumed that preconditioning’s protective signaling occurs in the cardiomyocyte. We critically tested that hypothesis by testing for the presence of each of these receptors in isolated adult rabbit ventricular myocytes that had been transfected with cyclic nucleotide-gated (CNG) ion channels. Because subsarcolemmal cAMP opens the CNG channels we could monitor cAMP levels within a single cardiomyocyte by measuring channel current with a patch pipette. The presence of a receptor would be confirmed if we could alter cAMP in the cell with a selective agonist to the receptor being studied. Superfusion with the β-adrenergic Gs-coupled receptor agonist isoproterenol (50 nM) transiently increased cAMP levels, and, therefore, channel current. Pretreatment with selective agonists to A1 or A3 adenosine receptors (AR) that are Gi-coupled markedly attenuated the response to isoproterenol indicating inhibition of adenylyl cyclase by increased Gi activity. Agonists to bradykinin or δ-opioid receptors also attenuated isoproterenol’s response. A2AAR and A2BAR are Gs-coupled. The A2AAR–selective agonist CGS21680 increased current through CNG channels but only in the presence of phosphodiesterase (PDE) inhibitors indicating low surface receptor activity and high intracellular PDE activity. As we previously reported, BAY 60–6583, an A2BAR-selective agonist which mimics preconditioning’s protection in rabbit heart, neither increased nor decreased membrane current in transfected cardiomyocytes, suggesting absence or a markedly limited number of A2BAR in the sarcolemma. However, RT-PCR of purified cardiomyocytes yielded an A2BAR band implying that rabbit cardiomyocytes do indeed express A2BAR. These data reveal that all receptors reported to be involved in ischemic preconditioning do exist on or within the cardiomyocyte.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

All Preconditioning-Related G Protein-Coupled Receptors Can Be Demonstrated in the Rabbit Cardiomyocyte

Xin

Yang

Rich

et al. 2011

J Cardiovasc Pharmacol Ther

View full text Add to dashboard Cite

show abstract

Bradykinin induced sustained anti–adrenergic actions in guinea pig heart muscle involves PKC

Abstract: Anti-beta-adrenergic effects of bradykinin on contractile force and action potential duration were demonstrated. PKC was important for the sustained effect on contractile force, but not for the acute effect and the effect on action potential duration.

Cited by 1 publication

References 20 publications

All Preconditioning-Related G Protein-Coupled Receptors Can Be Demonstrated in the Rabbit Cardiomyocyte

All Preconditioning-Related G Protein-Coupled Receptors Can Be Demonstrated in the Rabbit Cardiomyocyte

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