Inhibitory action of adenosine on histamine- and dopamine-stimulated cardiac contractility and adenylate cyclase in guinea pigs.

Baumann, Gert; Schrader, Jürgen; Gerlach, E.

doi:10.1161/01.res.48.2.259

Cited by 90 publications

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References 29 publications

(34 reference statements)

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“…However, in the same tissue (i.e., ventricular myocardium), neither the basal contractile force nor the increase in contractility caused by elevation of extracellular calcium or stimulation of a-adrenoreceptors is depressed by adenosine (Baumann et al, 1981;Endoh and Yamashita, 1980). Such observations have led to the conclusion that the inhibitory effects of adenosine in ventricular myocardium can be demonstrated only under conditions in which the adenylate cyclase-cAMP system of the heart has been previously stimulated (Schrader et al, 1977;Baumann et al, 1981). The present results confirm the findings that adenosine antagonizes the inotropic effect of isoproterenol, but additionally, shows that this antagonism also applies to the electrophysiological effects of isoproterenol.…”

Section: Discussionmentioning

confidence: 97%

“…Adenosine has been reported to antagonize the positive inotropic and metabolic effects of catecholi i amines in ventricular myocardium (Schrader et al, 1977;Dobson, 1978;Baumann et al, 1981). However, in the same tissue (i.e., ventricular myocardium), neither the basal contractile force nor the increase in contractility caused by elevation of extracellular calcium or stimulation of a-adrenoreceptors is depressed by adenosine (Baumann et al, 1981;Endoh and Yamashita, 1980).…”

Section: Discussionmentioning

confidence: 99%

“…We conclude, first, that isolated ventricular myocytes respond to isoproterenol and adenosine; second, that adenosine has no direct effect, but effectively antagonizes the stimulatory actions of isoproterenol; third, that findings are consistent with the ones reported for multicellular ventricular preparations; fourth, that adenosine concentrations required to attenuate the actions of isoproterenol are in the range of adenosine concentrations released by cardiac cells when oxygen availability is limited and/or demand is increased; and fifth, that endogenously released adenosine may modulate the electrophysiological and contractile effects of catecholamines. (Circ Res 53: 287-297, 1983) RECENTLY, adenosine has been recognized to antagonize specifically the inotropic, and some of the electrophysiological and metabolic, effects of catecholamines in ventricular myocardium (Schrader et al, 1977;Dobson, 1978;Baumann et al, 1981, Belardinelli et al, 1982.…”

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confidence: 99%

“…RECENTLY, adenosine has been recognized to antagonize specifically the inotropic, and some of the electrophysiological and metabolic, effects of catecholamines in ventricular myocardium (Schrader et al, 1977;Dobson, 1978;Baumann et al, 1981, Belardinelli et al, 1982.…”

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Actions of adenosine and isoproterenol on isolated mammalian ventricular myocytes.

Belardinelli¹,

Isenberg²

1983

Circulation Research

181

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SUMMARY. We investigated the effects of adenosine and isoproterenol on enzymatically dispersed ventricular myocytes from bovine and guinea pig hearts. Inrracellular stimulation of relaxed myocytes with regular srriation patterns and normal resting potential resulted in action potentials with full plateaus accompanied by contractions. Adenosine in concentrations up to 0.2 HIM had no significant effect on any of the action potential parameters or on the basal contractility. In contrast, in the same cells, adenosine effectively antagonized the stimulatory effect of isoproterenol. Isoproterenol (1-10 nM) prolonged the action potentials by 34-41%, displaced the plateau to more positive potentials, and caused a 3-fold increase in the extent of myocyte sarcomere shortening. In the presence of adenosine (5-50 HM), isoproterenol increased the action potential duration by only 8-9%, the shift of the plateau was nearly abolished, and the increase in the extent of myocyte sarcomere shortening was less than 10%. In some of the myocytes, isoproterenol (1-10 nM) induced depolarizing afterpotentials accompanied by aftercontractions. The afterdepolarizations occasionally reached threshold resulting in triggered sustained rhythmic activity. Adenosine (20-50 HM) not only reduced the amplitude of the afterdepolarizarions and aftercontractions, but also abolished the sustained rhythmic activity. We conclude, first, that isolated ventricular myocytes respond to isoproterenol and adenosine; second, that adenosine has no direct effect, but effectively antagonizes the stimulatory actions of isoproterenol; third, that findings are consistent with the ones reported for multicellular ventricular preparations; fourth, that adenosine concentrations required to attenuate the actions of isoproterenol are in the range of adenosine concentrations released by cardiac cells when oxygen availability is limited and/or demand is increased; and fifth, that endogenously released adenosine may modulate the electrophysiological and contractile effects of catecholamines. (Circ Res 53: 287-297, 1983) RECENTLY, adenosine has been recognized to antagonize specifically the inotropic, and some of the electrophysiological and metabolic, effects of catecholamines in ventricular myocardium (Schrader et al., 1977;Dobson, 1978;Baumann et al., 1981, Belardinelli et al., 1982.The observation that adenosine antagonizes the inotropic effect of tyTamine, but not the tyramineinduced release of norepinephrine, has been assumed to indicate that adenosine acts postsynaptically (Schrader et al., 1979). However, adenosine has also been shown to inhibit the stimulationinduced release of norepinephrine from sympathetic nerve terminals in the heart (Hedquist and Fredholm, 1976;Wakade and Wakade, 1978). Consistent with this latter finding, in the dog, adenosine has been shown to reduce the increase in heart rate induced by electric stimulation of the right stellate ganglion (Horn and Lokhandwala, 1981). These observations suggest that the antagonism between adenosine and sympa...

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Actions of adenosine and isoproterenol on isolated mammalian ventricular myocytes.

Belardinelli¹,

Isenberg²

1983

Circulation Research

181

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“…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].…”

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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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Cardiac electrophysiological actions of adenosine

et al. 1998

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Adenosine, an endogenous nucleoside, modulates heart functions via cell membrane receptors. This review focuses on the A1 adenosine receptor‐mediated electrophysiological effects on cardiac myocytes. Activation of A1 adenosine receptors leads to reductions of heart rate, atrioventricular nodal conduction, and atrial contractile force, and to an attenuation of the effects of β‐adrenergic stimulation on myocardium. The ionic mechanisms and the receptor‐effector coupling systems that underly the inhibitory effects of adenosine are discussed. Drug Dev. Res. 45:420–426, 1998. © 1998 Wiley‐Liss, Inc.

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Inhibitory action of adenosine on histamine- and dopamine-stimulated cardiac contractility and adenylate cyclase in guinea pigs.

Cited by 90 publications

References 29 publications

Actions of adenosine and isoproterenol on isolated mammalian ventricular myocytes.

Actions of adenosine and isoproterenol on isolated mammalian ventricular myocytes.

Characterization of adenosine receptors in intact cultured heart cells

Cardiac electrophysiological actions of adenosine

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