The physiological activity of adenine compounds with especial reference to their action upon the mammalian heart1

Drury, A. N.; Szent-Györgyi, A.

doi:10.1113/jphysiol.1929.sp002608

Cited by 1,369 publications

(538 citation statements)

References 6 publications

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“…These responses include negative chronotropic, dromotropic and ionotropic effects on the heart [7,8]. A 1 adenosine receptors in the heart also appear to mediate the attenuation of the positive inotropic effects of catecholamine [12,13,[41][42][43][44][45]].…”

Section: Discussionmentioning

confidence: 99%

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Characterization of adenosine receptors in intact cultured heart cells

El-Ani

Shainberg

1994

Biochemical Pharmacology

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Adenosine receptors were studied on heart cells grown in cultures by the radioligand binding technique. We used the hydrophilic A 1 adenosine receptor radioligand [ 3 H]-8-cyclopentyl-1,3-dipropylxanthine ([ 3 H]CPX), to monitor the level of the receptors on intact cardiocytes. The binding showed high affinity (K d = 0.13 nM) and the number of [ 3 H]CPX binding sites (B max ) was 23.1 fmol/dish (21 fmol/mg protein). The K i of the agonists R-N 6 -(2-phenylisopropyl)-adenosine (R-PIA) and S-N 6 -(2-phenylisopropyl)-adenosine (S-PIA), and of the antagonists CPX and theophylline were 3.57, 49.0, 1.63 and 4880 nM, respectively. The number of adenosine receptors was very low during the first days in cultures (5 fmol/dish) and increased gradually until it reached a plateau on days 8-10. Treatment with norepinephrine or isoproterenol which accelerated the rate of contractions, induced up regulation of the receptors. B max increased 2-3-fold by application of norepinephrine for 4 days, while receptor affinity to the radioligand was unaffected. Lactate dehydrogenase (LDH) and creatine kinase (CK) activity increased only by 22 and 38%, respectively. Similarly, 3 days treatment with triiodothyronine (T 3 , 10 −8 M), which also accelerated heart rate, increased the number of adenosine receptors by 56% without a significant change in the affinity of the receptors to [ 3 H]CPX. Carbamylcholine (5 × 10 −6 M), which reduced the rate of heart contractions, caused 26% down regulation while the affinity of the receptors remained unchanged. It is concluded that there is a linkage between the rate of cardiac contractions and the level of adenosine receptors. Thus, the level of adenosine receptors may respond to drug-induced chronic changes in cardiac contractile activity so as to restore conditions to normal (basal) contractions. KeywordsCPX; heart-rate; norepinephrine; thyroid hormones Adenosine modulates a variety of physiological functions in the heart. These actions are mediated by cell surface adenosine receptors, which can be classified into A 1 and A 2 † Corresponding author. Tel. (972)3-5318265; FAX (972)3-5351824. In conditions of stress like hypoxia or ischemia, the concentration of adenosine in the extracellular fluid rises dramatically, mainly through the breakdown of ATP [4]. In these conditions adenosine has therapeutic and protective effects on the heart [5,6]. Adenosine causes negative chronotropic, dromotropic and ionotropic effects on the cardiac tissue via A 1 receptors [7,8]. Adenosine also acts as a coronary vasodilator via A 2 receptors [9]. These effects of adenosine occur also without prior catecholamine treatment [10]. Stimulation that enhances the cAMP content (catecholamines, forskolin, amrinone), makes the heart more sensitive to adenosine [11][12][13][14]. In addition, adenosine causes hyperpolarization by activation of K + channels [15] via G proteins [16, 17]. These K + channels are the same channels that are stimulated by acetylcholine in the cardiac tissue [18][19][20]. HHS Public AccessChron...

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Section: Discussionmentioning

confidence: 99%

“…In these conditions adenosine has therapeutic and protective effects on the heart [5,6]. Adenosine causes negative chronotropic, dromotropic and ionotropic effects on the cardiac tissue via A 1 receptors [7,8]. Adenosine also acts as a coronary vasodilator via A 2 receptors [9].…”

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confidence: 99%

Characterization of adenosine receptors in intact cultured heart cells

El-Ani

Shainberg

1994

Biochemical Pharmacology

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“…Although the physiological role of extracellular purine nucleotides has been implicated early in the 20 th century by Szent-Györgyi and his co-worker [1], it was not until the seminal work of Burnstock and colleagues on non-adrenergic non-cholinergic transmission in the taenia coli [2] that they gained proper acceptance into the growing community of signalling molecules. Since then purinergic signalling (coined by Burnstock [3]; see also [4]) has been widely accepted in nearly all eukaryotic organisms [5].…”

Section: Brief Overview Of Purinergic Signallingmentioning

confidence: 99%

“…Today seven members of the ionotropic (P2X [1][2][3][4][5][6][7] ) and eight members of the metabotropic (P2Y 1,2,4,6,[11][12][13][14] ) purinergic receptors have been cloned and identified in mammals [13,14]. In 6 case of P2X receptors the seven members of the subfamily refer to seven distinct subunits as discussed below.…”

Section: P2 Receptorsmentioning

confidence: 99%

Purinergic signalling-evoked intracellular Ca2+ concentration changes in the regulation of chondrogenesis and skeletal muscle formation

et al. 2016

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“…Adenosine was first recognized as a physiologic regulator of coronary vascular tone by Drury and Szent-Gyorgy in 1929 [1]. However, it was not until 1970 that Sattin and Rall [2] showed that adenosine regulates cell function via occupancy of specific receptors on the cell surface.…”

Section: Introductionmentioning

confidence: 99%

Adenosine in fibrosis

Chan¹,

Cronstein²

2009

Mod Rheumatol

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Adenosine is an endogenous autocoid that regulates a multitude of bodily functions. Its anti-inflammatory actions are well known to rheumatologists since it mediates many of the anti-inflammatory effects of a number of antirheumatic drugs such as methotrexate. However, inflammatory and tissue regenerative responses are intricately linked, with wound healing being a prime example. It has only recently been appreciated that adenosine has a key role in tissue regenerative and fibrotic processes. An understanding of these processes may shed new light on potential therapeutic options in diseases such as scleroderma where tissue fibrosis features prominently.

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The physiological activity of adenine compounds with especial reference to their action upon the mammalian heart1

Cited by 1,369 publications

References 6 publications

Characterization of adenosine receptors in intact cultured heart cells

Characterization of adenosine receptors in intact cultured heart cells

Purinergic signalling-evoked intracellular Ca2+ concentration changes in the regulation of chondrogenesis and skeletal muscle formation

Adenosine in fibrosis

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