Effects Of Exogenous Adenosine Research Articles

Microdialysis Elevation of Adenosine in the Basal Forebrain Produces Vigilance Impairments in the Rat Psychomotor Vigilance Task

The inhibitory neuromodulator adenosine has been proposed as a homeostatic sleep factor that acts potently in the basal forebrain (BF) to increase sleepiness. Here 300 microM of adenosine was dialyzed in the BF of rats, and the effect on vigilance was determined in the rat Psychomotor Vigilance Task (rPVT). Rats experienced all experimental conditions in a repeated-measures, cross-over design. Twelve young adult male Fischer-Norway rats. Sustained attention performance in the rPVT was evaluated following 2 hours of bilateral microdialysis perfusion of vehicle, adenosine (300 microM), or codialysis of 300 microM of adenosine with the A1 receptor antagonist 8-cyclopentyltheophylline. During rPVT performance, response latencies and performance lapses increased significantly after adenosine dialysis when compared with baseline (no dialysis) or vehicle dialysis sessions. The codialysis of 8-cyclopentyltheophylline with adenosine completely blocked the effects produced by adenosine alone, resulting in performance equivalent to that of the vehicle sessions. Pharmacologic elevation of BF adenosine in rats produced vigilance impairments resembling the effect of sleep deprivation on vigilance performance in both man and rats. This effect of exogenous adenosine was completely blocked by codialysis with an adenosine A1 receptor antagonist. The results are consistent with the hypothesis that sleep loss induces elevations of BF adenosine that, acting via A1 receptors, lead to increased sleepiness and impaired vigilance.

Effect of exogenous adenosine and monensin on glycolytic flux in isolated perfused normoxic rat hearts: Role of pyruvate kinase

We studied the effect of exogenous adenosine in isolated perfused normoxic rat hearts on glycolytic flux through pyruvate kinase (PK). We compared its effect with that of myxothiazol, an inhibitor of mitochondrial ATP production. Moreover, we tested whether an increase of membrane ionic flux with monensin is linked to a stimulation of glycolytic flux through PK. After a 20-min stabilization period adenosine, myxothiazol or monensin were administrated to the perfusate continuously at various concentrations during 10 min. The contraction was monitored and the lactate production in coronary effluents evaluated. The amount of adenine nucleotides and phosphoenolpyruvate was measured in the frozen hearts. Myxothiazol induced a decrease of the left ventricular developed pressure (LVDP : -40%) together with a stimulation of glycolytic flux secondary to PK activation. In contrast, adenosine primarily reduced heart rate (HR: -30%) with only marginal effects on LVDP. This was associated with an inhibition of glycolysis at the level of PK. The Na+ ionophore monensin affected HR (+14%) and LVDP (+25%). This effect was associated with a stimulation of glycolysis secondary to the stimulation of PK. These results provide new information of action of adenosine in the heart and support the concept of a direct coupling between glycolysis and process regulating sarcolemmal ionic fluxes.

Multiple effects of adenosine in the arterially perfused mammalian eye. Possible mechanisms for the neuroprotective function of adenosine in the retina.

It has been postulated that the major physiological role of adenosine is protection of the central nervous system in conditions such as ischemia, hypoxia, or prolonged neuronal excitation. Under these conditions adenosine is released, and exerts multiple effects, including vasodilation, inhibition of neuronal activity, and enhancement of glycogenolysis, resulting in neuroprotection. In this article, published as well as unpublished data on the multiple effects of exogenous adenosine and application of adenosine-related agents, performed using the arterially perfused cat eye, will be reviewed and discussed within the framework of the neuroprotective role of adenosine. The isolated, arterially perfused eye preparation has the advantage of combining integrity of the eye structure, exact control of arterial concentration and timing of applied pharmacological agents, and access to electrophysiological parameters of both retina and optic nerve, as well as the ability to control and monitor perfusate flow. The absence of red blood cells in the perfusate prevents adenosine from being metabolized prior to reaching the eye.

Adenosine in Myocardial Protection given through Three Windows of Opportunity. An Experimental Study with Pigs

Objective –Adenosine (ADO) has been shown to have beneficial effects against tissue injury after myocardial ischemia. However, the timing and dose of ADO administration have not been defined. This study was designed to determine the cardioprotective effect of exogenous ADO in an experimental open heart surgery model in pigs. Design –The animals were openly divided into two groups both undergoing 30 min of total cardiac arrest. In the control group animals received cold crystalloid cardioplegic solution. In the ADO group ADO was added to cardioplegic solution and in addition ADO was infused to the superior vena cava for 2 h starting 30 min before cardiac arrest. The pumping function of the heart was measured with echocardiography and myocardial blood flow was measured with microspheres and positron emission tomography (PET). Cardiomyocyte apoptosis was detected and tumor necrosis factor (TNF) levels were measured. Results –Better post-ischemic pumping function was found in the ADO group (relative decrease 43.7% vs 55.4%, p = 0.20 between the groups). The cardiac output decreased significantly from the baseline values ( p < 0.05 in both groups). There was a temporary decrease in myocardial blood flow post-ischemically, followed by a compensatory increase during the later reperfusion period. The cardiomyocyte apoptosis was induced significantly in both groups. Conclusions –In this experiment two important details were noticed. Firstly, cardiomyocyte apoptosis is involved in ischemia-reperfusion injury associated with open heart surgery. Secondly, PET is a comparable method with the microsphere technique when coronary flow is studied. No significant effects of ADO against ischemia-reperfusion injury could be shown. However, there were some signs of positive outcome, even though statistical significance could not be reached.

Characterization of Ca2+ influx through recombinant P2X receptor in C6BU-1 cells.

1. The effects of exogenous adenosine 5'-triphosphate (ATP) and alpha,beta-methylene ATP (alpha,beta meATP) on C6BU-1 cells transfected with P2X2 and P2X3 subtypes, separately or together (P2X2+3), were investigated using fura-2 fluorescence recording and whole-cell patch clamp recording methods. 2. Untransfected C6BU-1 cells showed no intracellular Ca2+ ([Ca2+]i) increase in response to depolarizing stimulation with high K+ or stimulation with ATP. There was no current induced by ATP under voltage clamp conditions in untransfected C6BU-1 cells. ATP caused Ca2+ influx only from extracellular sources in C6BU-1 cells transfected with the P2X subtypes, suggesting that the C6BU-1 cell line is suitable for the characterization of Ca2+ influx through the P2X subtypes. 3. In C6BU-1 cells transfected with the P2X2 subtype, ATP (more than 10 microM) but not alpha,beta meATP (up to 100 microM) evoked a rise in [Ca2+]i. 4. In the cells transfected with the P2X3 subtype, current responses under voltage clamp conditions were observed at ATP concentrations higher than 0.1 microM of alpha,beta meATP were required. This discrepancy in the concentration dependence of the agonist responses with respect to the [Ca2+]i rise and the current response was seen only with the P2X3 subtype. In addition, the agonist-induced rise in [Ca2+]i was observed only after the first application because of desensitization of this subtype. 5. In C6BU-1 cells co-transfected with P2X2 and P2X3, ATP at 1 microM evoked a [Ca2+]i rise. This responsiveness was higher than that of the other subtype combinations tested. The efficiency of expression was improved by co-transfection with P2X2 and P2X3, when compared to transfection with the P2X3 subtype alone. The desensitization of the P2X2+3 was apparently slower than that of the P2X3 subtype alone. Therefore, this combination could respond to the repeated application of agonists each time with a [Ca2+]i rise. 6. These results suggest that the P2X2 and P2X3 subtypes assemble a heteromultimer and that this heterogeneous expression acquires more effective Ca2+ dynamics than that by homogeneously expressed P2X2 or P2X3.

Two types of P2x-purinoceptors in neurons of the guinea pig ileum submucous plexus

Effects of exogenous adenosine 5′-triphosphate (ATP) on dissociated guinea pig ileum submucous neurons were studied using a conventional whole-cell patch-clamp technique. With the holding potential of −50 mV, application of 50–1,000 μM ATP evoked an inward current (ATP-induced current) in most (90%) of the tested neurons (n-35). ATP-induced currents were observed regardless of whether or not guanosine 5′-triphosphate (GTP, 0.2 mM) and ATP (2 mM) were present in the intracellular solution, or GTP was replaced with equimolar concentration of guanosine 5′-O-3-thiotriphosphate (n-5). In 26 of 29 neurons studied, which responded to ATP, applications of 50–1,000 μM ATP induced slowly declining currents. ATP receptors did not appear to be completely desensitized during a long pulse (up to 4 min) of 200 μM ATP. Suramin (200 μM) accelerated an increase to peak of the current induced by 200 μM ATP without affecting the maximum response amplitude (n−4_. In about 10% of the neuronsn−3), 50 μM ATP evoked rapidly declining (about 1 sec) currents. Application of 100 μM α,β-Me-ATP to these neurons evoked similar responses. The above results suggest that submucous neurons express two specific subtypes of ionotropic P2x-purinoceptors, which might be involved in distinct excitatory processes in these neurons.

Effect of exogenous adenosine and its monophosphate on the contractile response to acetylcholine in the human isolated detrusor muscle strips.

1. Adenosine (0.1-1 mM) or its 5'-monophosphate (5'-AMP) induced a concentration-dependent relaxation of tension caused by acetylcholine (0.2 microM) in human urinary bladder detrusor strips. 2. This effect was antagonized concentration dependently by theophylline at an apparent pA2 value of about 5. 3. Maximum relaxation by adenosine or 5'-AMP never exceeded 50% and 80%, respectively, of acetylcholine-induced tension. Relaxation by some beta2-adrenoceptor agonists (0.1-0.2 mM) or norepinephrine was limited to about 50% of maximum. 4. The responses to adenosine and terbutaline were additive, causing full relaxation, and suggesting mobilization of distinct mechanisms underlying muscle relaxation.

The effect of exogenous adenosine on functional injury caused by hydrogen peroxide in the isolated rat heart.

Adenosine is an endogenous cardioprotective substance. The present study examines whether exogenous adenosine attenuates cardiac injury induced by oxidative stress. Rat hearts (Langendorff model) were perfused with H2O2 (180 microM) for 10 min, then recovered for 60 min (n = 10). In other groups adenosine 55 microM, 11 0 microM, or 220 microM (n = 10 in each) was given in addition to H2O2 throughout perfusion. Control perfusion with Krebs Henseleit only (n = 7), adenosine 110 microM throughout perfusion (n = 7), and adenosine 110 microM as an intervention (n = 7) was performed. The hearts were paced at 320 beats/min. Left ventricular systolic (LVSP) and end-diastolic (LVEDP) pressures were measured together with coronary flow (CF), and left ventricular developed pressure (LVDP = LVSP - LVEDP) was calculated. H2O2 decreased LVSP from 105 +/- 8 to 60 +/- 5 mmHg (mean +/- SEM) after 10 min infusion (p < 0.008). Adenosine did not attenuate the decrease of LVSP. LVEDP increased from 0 to 59 +/- 10 mmHg (p < 0.004) and 62 +/- 11 mmHg 5 and 15 min after end of infusion of H2O2, respectively. Neither 55 microM nor 220 microM adenosine inhibited the H2O2-induced increase of LVEDP. Adenosine 110 microM attenuated the increase after 15 (15 +/- 4 mmHg, p < 0.004) and 25 min observation (26 +/- 7 mmHg, p < 0.012). Adenosine did not attenuate the reduction of LVDP. CF initially increased during infusion of H2O2, thereafter decreased. Hearts given adenosine had higher basal CF, and CF did not increase after H2O2. Control perfusion with adenosine, given throughout perfusion or as an intervention, increased CF and tended to increase LVSP. In summary, adenosine did not inhibit H2O2-induced depression of contractility or reduction of CF. One concentration of adenosine (110 microM) attenuated H2O2-induced impairment of relaxation. Exogenous adenosine does not have an important influence on functional injury caused by exogenous oxidants.

Colocalization of ATP and nicotinic ACh receptors in the identified vagal preganglionic neurone of rat.

1. Effects of exogenous adenosine 5'-triphosphate (ATP) and acetylcholine (ACh) were investigated on acutely dissociated preganglionic neurones in the dorsal motor nucleus of vagus (DMV) of rats using whole-cell patch clamp recording methods. 2. The DMV neurones identified by retrograde transport of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) fixed onto the cervical vagal nerve bundle were large in size (25-35 microns diameter) and bipolar or tripolar in shape. 3. About 90% of DiI labelled DMV neurones responded to both ATP (10(-4) M) and ACh (10(-4) M) with inward currents at a holding potential (Vh) of -40 mV. 4. The ATP-induced current (IATP) and the ACh-induced current (IACh) reversed their polarities at membrane potentials between +5 and +15 mV, indicating that ATP and ACh increase the membrane permeability to cations. 5. The inhibitory potency of Reactive Blue on 5 x 10(-4) M IATP is more effective (concentration for half-inhibition (IC50), 4.4 x 10(-7) M) than suramin (IC50, 6.0 x 10(-6) M). In addition, alpha,beta-methylene ATP up to 10(-4) M could not induce any current. As intracellular application of guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) did not block the IATP, the IATP was mediated not by guanosine triphosphate (GTP) binding protein, but rather by ligand-gated ionic channels, presumably via P2X receptors. 6. Currents produced by ACh were due to activation of nicotinic receptors because they were mimicked by nicotine and carbachol, and blocked by hexamethonium. In addition, muscarine evoked no response. 7. Only 25% of nucleus tractus solitarii (NTS) neurones and no hypoglossal neurones responded to the exogenous application of ATP. 8. These results suggest that vagal preganglionic neurones colocalize functionally nicotinic and P2X purinergic receptors.

Effects of adenosine in simulated ischemia and reperfusion in guinea pig ventricular myocytes

Effects of adenosine (ADN) on cardiac cellular electrical and contractile activity were determined during ischemia and reperfusion. Electrical activity was recorded with conventional and voltage-clamp techniques. Contractions were monitored with a video edge detector. Myocytes were exposed to simulated ischemia (20 min), in the presence or absence of ADN (1-50 microM), and reperfused with Tyrode solution. ADN had no effects under control conditions. However, action potential abbreviation during ischemia was greater in the presence of ADN than for control, and recovery was delayed. In ischemia, Ca2+ current declined equally, and contractions were abolished in control and ADN-treated myocytes. In early reperfusion, oscillatory afterpotentials (OAP), transient inward current (ITI) and aftercontractions appeared, and contractions increased above preischemic levels. ADN abolished contractile overshoot and reduced incidence of OAP, ITI, and aftercontractions from 78 to 37.5%. The effects of exogenous ADN were inhibited by ADN A1-receptor blockade. Inhibition of endogenous ADN by 8-phenyltheophylline only increased incidence of ITI. Thus exogenous ADN in ischemia may protect the myocardium in reperfusion via A1 receptors.

Mechanism of the ATP-induced rise in cytosolic Ca2+ in freshly isolated smooth muscle cells from human saphenous vein.

Effects of exogenous adenosine 5'-triphosphate (ATP) were studied by measurements of intracellular Ca2+ concentration ([Ca2+]i) and membrane currents in myocytes freshly isolated from the human saphenous vein. At a holding potential of -60 mV, ATP (10 microM) elicited a transient inward current and increased [Ca2+]i. These effects of ATP were inhibited by alpha,beta-methylene adenosine 5'-triphosphate (AMP-CPP, 10 microM). The ATP-gated current corresponded to a non-selective cation conductance allowing Ca2+ entry. The ATP-induced [Ca2+]i rise was abolished in Ca(2+)-free solution and was reduced to 30.1 +/- 5.5% (n = 14) of the control response when ATP was applied immediately after caffeine, and to 23.7 +/- 3.8% (n = 11) in the presence of thapsigargin. The Ca(2+)-induced Ca2+ release blocker tetracaine inhibited the rise in [Ca2+]i induced by both caffeine and ATP, with apparent inhibitory constants of 70 microM and 100 microM, respectively. Of the ATP-induced increase in [Ca2+]i 29.3 +/- 3.9% (n = 8) was tetracaine resistant. It is concluded that the effects of ATP in human saphenous vein myocytes are only mediated by activation of P2x receptor channels. The ATP-induced [Ca2+]i rise is due to both Ca2+ entry and Ca2+ release activated by Ca2+ ions that enter the cell through P2x receptor channels.

Feedback regulation of Na channels in rat CCT. III. Response to cAMP.

The effects of exogenous adenosine 3',5'-cyclic monophosphate (cAMP) on apical Na channels in the rat cortical collecting tubule were studied using the patch-clamp technique and fura 2 fluorescence measurements of intracellular Ca2+ (Ca2+i). When the permeant analogue, 8-(4-chlorophenylthio)-cAMP (CPT-cAMP, 200 microM), was added to the superfusate during recording from cell-attached patches, both the mean number of open channels (NPo) and the single-channel current (i) decreased within 3 min. When the superfusate also contained amiloride (10 microM), there was no effect of CPT-cAMP on either NPo or i. When CPT-cAMP was added to the bath before formation of the patch, the density of conducting channels was increased from 10 +/- 2 to 37 +/- 6 per patch, as estimated by analysis of channel-induced noise. This suggests that cAMP increases open-channel density in the regions of the apical membrane outside the patch but not within the patch. Channels already active in the patch before stimulation with the nucleotide are subject to feedback inhibition secondary to increased Na entry into the cell. CPT-cAMP increased Ca2+i from 104 to 198 nM. This increase in Ca2+i was abolished by benzamil (0.5 microM) or by low extracellular Ca2+. The cAMP-dependent reduction in NPo was still observed in Ca(2+)-free medium, indicating that a rise in Ca2+i was not essential for the feedback response. The decrease in NPo was attenuated, however, when cAMP was added in the absence of Ca2+ and in the presence of ouabain (1 mM) in the superfusate.(ABSTRACT TRUNCATED AT 250 WORDS)

The Effect of Exogenous Adenosine in Patients with Neurally‐Mediated Syncope and Sick Sinus Syndrome

The effects of a 20-mg i.v., bolus of adenosine 5' triphosphate (ATP) on the heart rhythm was studied in 79 patients affected by neurally-mediated syncope (26 cases) or sick sinus syndrome (22 cases) or both syndromes (31 cases) and in 31 healthy control subjects in order to examine the sensitivity of cardiac purinoceptors in such circumstances. During ATP infusion, the sinus cycle lengthened to > 2 seconds in no control, in 1 (4%) patient with neurally-mediated syncope, in 5 (23%) patients with sick sinus syndrome, and in 13 (42%) patients with both neurally-mediated and sick sinus syndromes (P = 0.01). Atrioventricular block occurred in 14 (45%) of controls, in 10 (38%) patients with neurally-mediated syncope, in 4 (18%) patients with sick sinus syndrome, and in 13 (42%) patients with both neurally-mediated syncope and sick sinus syndrome (n.s.). Thus, exogenous ATP exerts different effects on patients with neurally-mediated syncope and patients with sick sinus syndrome. In fact, intrisic disease of the sinus node is necessary to modulate an abnormal adenosine-mediated sinus arrest, whereas patients affected by neurally-mediated syncope alone show a normal sensitivity to the drug administration. The effect of ATP on atrioventricular conduction is greater than that on sinus node and is of similar magnitude in patients and controls; thus the clinical meaning of ATP induced atrioventricular block remains uncertain.

ATP released together with acetylcholine as the mediator of neuromuscular depression at frog motor nerve endings.

1. The hypothesis that ATP released by presynaptic stimulation is hydrolysed to adenosine and mediates prejunctional neuromuscular depression was tested at vertebrate neuromuscular junctions. Electrophysiological recordings of evoked acetylcholine (ACh) release and perineural ionic currents at motor nerve endings were made using the frog cutaneous pectoris nerve-muscle preparation. Either tubocurarine or alpha-bungarotoxin was used to block muscle contractions. 2. Either alpha,beta-methylene ADP (which inhibits ecto-5'nucleotidases and thus prevents the degradation of ATP to adenosine) or selective adenosine receptor antagonists (8-cyclo-pentyl alkyl xanthines) prevented the inhibitory effects of exogenous ATP on ACh release in response to low-frequency nerve stimulation. These results confirm earlier findings that ATP must be hydrolysed to adenosine to inhibit ACh release. 3. The presence of alpha,beta-methylene ADP completely prevented neuromuscular depression in response to repetitive high-frequency nerve stimulation (0.5-1 Hz). alpha,beta-Methylene ADP had no effect on ACh secretion under conditions where ACh release is well maintained (low-frequency stimulation, 0.05 Hz). 4. Selective adenosine receptor antagonists completely eliminated neuromuscular depression produced by repetitive high-frequency nerve stimulation (1.0 Hz) but had no effect on ACh release at low frequencies of stimulation (0.05 Hz). 5. Exogenous adenosine deaminase (5 i.u. ml-1), which degrades adenosine to its inactive nucleoside inosine, also eliminated neuromuscular depression but had no significant effect on ACh release at frequencies of nerve stimulation too low to produce prejunctional depression. 6. During maximal neuromuscular depression, the effects of exogenous adenosine or 2-chloroadenosine, an adenosine agonist, were occluded. 7. The calcium-sensitive component of perineurial recordings of motor nerve terminal currents did not change during depression or during application of adenosine receptor antagonists and adenosine deaminase, suggesting that neuromuscular depression in this species was not associated with changes in presynaptic Ca2+ currents. 8. These results suggest that, under the conditions of these experiments, endogenous ATP, after hydrolysis to adenosine, causes prejunctional neuromuscular depression. This inhibitory effect of endogenous adenosine occurs at a site distal to the locus of Ca2+ entry in the frog.

Effects of adenosine and angiotensin on macula densa-stimulated renin secretion

The present studies were performed to assess, in the isolated perfused juxtaglomerular apparatus of the rabbit kidney, the effect of exogenous adenosine on renin secretion stimulated by a low NaCl concentration at the macula densa. Addition of adenosine to the bath resulted in a change of renin secretion from 30.4 to 23.9 nGU/min at an adenosine concentration of 10(-6) M (n = 7; P = NS), from 38.6 to 17.9 nGU/min at a concentration of 10(-4) M (n = 7; P = 0.038), and from 18.4 to 5.8 nGU/min at 10(-2) M (P = 0.0053). Addition of the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine at 10(-5) M fully reversed the effect of adenosine at 10(-4) M, but not at 10(-2) M. Inhibition of adenosine breakdown by the adenosine deaminase inhibitor pentostatin (10(-6) M) enhanced the inhibitory effect of adenosine with renin secretion falling from 61.7 to 19.5 nGU/min at 10(-6) M adenosine (P = 0.035) and from 44.7 to 13.5 nGU/min at 10(-4) M adenosine (n = 0.027). A marked inhibition of NaCl-dependent renin secretion was caused by both angiotensin II (P = 0.011) and angiotensin III (P = 0.006), both at 10(-8) M. These results show that adenosine is capable of reducing macula densa-mediated renin secretion, but that this effect, even at very high concentrations or during adenosine deaminase blockade, does not fully mimic the inhibitory potency of increasing luminal NaCl concentration. Because the marked effect caused by angiotensins establishes the potential of this preparation to demonstrate inhibitory hormonal influences, it is concluded that adenosine does not appear to be the sole paracrine factor responsible for the NaCl-induced reduction of renin secretion.

Activation of cardiac sympathetic afferents: effects of exogenous adenosine and adenosine analogues.

Adenosine is released during myocardial ischemia and can cause angina-like chest pain when given by intracoronary administration. We tested the hypothesis that intracoronary adenosine activates cardiac sympathetic afferent fibers and results in reflex sympathoexcitation. In dogs with sinoaortic denervation and vagotomy, we administered 2 mg of adenosine into the left anterior descending artery over 2 min. Before dipyridamole infusion, intracoronary adenosine resulted in no change in blood pressure or renal sympathetic nerve activity. After dipyridamole infusion, which blocks adenosine uptake, intracoronary adenosine resulted in a peak increase in sympathetic activity of 34 +/- 7%. We also investigated the adenosine-receptor subtype responsible for this sympathoexcitatory response. We found that the adenosine1 agonist N6-cyclopentyladenosine elicited a dose-dependent sympathoexcitatory response similar to adenosine but that the adenosine2 agonist 5'-(N-cyclopropyl)carboxamidoadenosine failed to elicit a sympathoexcitatory response. We conclude that adenosine activates cardiac sympathetic afferent fibers and leads to a sympathoexcitatory response due to activation of adenosine1 receptors.

Purinergic receptors as a regulatory process of luminescence in Porichthys' luminous organs

AbstractThe effects of exogenous adenosine and adenine phosphorylated derivatives were tested on the adrenergic luminescence of isolated luminous organs of the fish Porichthys. Adenosine triphosphate, at concentrations ranging from 10−5M to 10−2M, strongly inhibited the two peaks of the biphasic‐shaped light emission induced by adrenalin. Adenosine diphosphate mimicked the effects of ATP, whereas adenosine monophosphate (AMP) and cyclic‐AMP were ineffective. Adenosine had no inhibitory effect but potentiated the first peak of light whose intensity was five times increased. It is concluded that P2‐purinergic receptors might be present on photocytes and exert a negative control on the luminescent system. Adenosine‐induced potentiation might be related to an intracellular effect of this compound.

Adenosine and hemodynamic alterations in cirrhotic rats

This study evaluated the hypothesis that adenosine may participate in the hemodynamic alterations observed in conscious unrestrained cirrhotic rats. In sham-operated rats, adenosine (20 micrograms.100 g body wt-1.min-1 iv) induced hyperdynamic circulation and significantly increased portal pressure, mimicking the hemodynamic changes observed in cirrhosis. Although adenosine significantly increased hyperdynamic circulation and portal pressure in cirrhotic rats, these changes were significantly less marked than in sham-operated rats. 8-Phenyltheophylline (20 micrograms.100 g body wt-1.min-1 iv), a specific and potent adenosine antagonist, significantly decreased portal tributary blood flow in sham-operated rats (-18.0 +/- 5.6%) but did not have a significant effect in cirrhotic rats. The limited effect of 8-phenyltheophylline was not due to an insufficient dose, since the dose administered antagonized the hemodynamic effect of exogenous adenosine up to 40 micrograms.100 g body wt-1.min-1. We conclude that in certain circumstances, although adenosine may aggravate the hyperdynamic circulation, in normal conditions, the hemodynamic alterations observed in cirrhotic rats are not mediated by adenosine.

Effect of an adenosine receptor antagonist on acute amphotericin B nephrotoxicity

The clinical usage of amphotericin B in treating systemic fungal infections is limited by its nephrotoxicity, which is caused by reductions in renal blood flow and alterations in renal tubular function. Aminophylline, an adenosine receptor antagonist, attenuates amphotericin B-induced reductions in renal blood flow in both dogs and rats, which suggests that endogenous adenosine may participate in this response. However, aminophylline per se is a vasodilator and also changes intracellular levels of cyclic nucleotides and calcium. In this study, we re-examined the hypothesis that adenosine participates in amphotericin B-induced renal vasoconstriction by employing a novel adenosine receptor antagonist, 1,3-dipropyl-8-(p-sulfophenyl)xanthine (DPSPX). This antagonist because of its negative charge at physiological pH, has limited access to the intracellular space. In a group of male Sprague-Dawley rats, an extracorporeal shunt was established between the carotid artery and left renal artery, via an aortic pouch, such that flow through the shunt was equivalent to renal blood flow. Also, a catheter was inserted into the left ureter for collection of urine and measurement of creatinine and electrolyte excretion. Amphotericin B-induced changes in renal blood flow and renal excretory function were measured in both control rats and rats pretreated with DPSPX at a dosage that abolishes the renovascular effects of exogenous adenosine in this model. In both control rats and rats pretreated with DPSPX, amphotericin B caused a marked decrease in renal blood flow, creatinine excretion, and potassium excretion; however, these effects of amphotericin B were similar in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Exogenous Adenosine in a Patient with Transplanted Heart. Evidence for Adenosine as a Messenger in Angina Pectoris

In this pilot study some cardiac effects of exogenous adenosine on the denervated heart were studied in a patient with transplanted heart since 3 years. He was instrumented with catheters into the left coronary artery, the coronary sinus and the right ventricle. Adenosine was given in increasing doses intracoronarily, into the aorta at the diaphragmal level and into a peripheral vein. When given into the aorta pain was provoked dose-dependently and not different from a reference group. When given intracoronarily no pain was provoked except at the highest dose when a slight discomfort of the chest was provoked. After intravenous injection no pain was provoked in the chest or in adjacent structures. Coronary sinus flow increased dose-dependently and not different from the reference group. No increased heart rate response occurred after intravenous or intracoronary injections. Extensive degrees of sinus and AV nodal blockade occurred. In conclusion, the results are in keeping with a role for adenosine as a messenger between myocardial ischaemia and angina pectoris and cardiac sympathetic pressure response. The importance of innervation for proper sinus and AV nodal function was also illustrated.