Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT02427 (Atropine)
 3,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The right atrium isolated from the dog heart was perfused through the cannulated sinus node artery with heparinized arterial blood led from a support dog anesthesized with 30 mg/Kg of sodium pentobarbital. When adenosine was administered into the sinus node artery, negative chronotropic and inotropic effects were dose-relatedly induced. The threshold dose for inducing the negative ones was 0.3 mug. Even a large dose level of 100 mug of adenosine did not cause sinus arrest although a profound sinus deceleration was induced. Adenosine action was suppressed by treatment with caffeine both in chronotropism and in inotropism. On the other hand, ACh induced only negative inotropic effect at a dose range of 0.01-0.03 mug. At 0.1 mug, ACh produced a significantly negative chronotropic effect. A large amount of 3-10 mug of ACh usually caused sinus arrest. Atropine treatment inhibited a negative chronotropic effect much more readily than a negative inotropic one. Although ACh action was enhanced by physostigmine, the difference of threshold doses remained unchanged even after physostigmine treatment. From these results, either adenosine or ACh depresses both SA nodal pacemaker activity and atrial contractile force and there may be the difference of receptor density for ACh between the SA node and atrial tissue.
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PMID:Differences in chronotropic and inotropic responses of canine atrial muscle and SA node pacemaker activity to adenosine and ACh. 93 49

The effects of various vasodilators on the uterine vascular bed were investigated in nonpregnant, oophorectomized sheep with chronically implanted flow probes and catheters inserted into branches of the uterine arteries. A 1 mug dose of estradiol-17beta (0.224 muM) produces a maximum uterine blood flow response after intra-arterial injection. Adenosine (24 muM) and bradykinin (0.02 muM) were observed to increase blood flow to levels achieved by 1 mug of estradiol-17beta. Acetylcholine, isoproterenol, and histamine were less potent in their vasodilator activity. Atropine, propanolol, and diphenhydramine did not inhibit the increase of uterine blood flow induced by estrogens.
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PMID:The effect of various vasoactive compounds upon the uterine vascular bed. 126

Atropine-resistant longitudinal contractions of the guinea-pig ileum due to field stimulation were greatly augmented by theophylline (150 microM). Adenosine exerted an opposite effect. Theophylline did not potentiate contractions evoked by exogenous substance P. It is suggested that a theophylline-sensitive inhibitory mechanism (possibly mediated by adenosine or a related substance) controls transmitter release from enteric non-cholinergic excitatory neurones.
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PMID:Theophylline-sensitive modulation of non-cholinergic excitatory neurotransmission in the guinea-pig ileum. 299 77

The characteristics of smooth muscle responses to transmural nerve stimulation in the rabbit iris sphincter were examined. Transmural stimulation elicited a composite contractile response that could be divided in two phases. Atropine abolished the phase I contraction and inhibited the phase II contraction. The atropine-resistant component of the phase II contraction which was unaltered by sympathetic denervation, was mimicked by substance P and abolished by capsaicin. Adenosine inhibited the phase I contraction. The adenosine analogue L-N6-phenylisopropyladenosine (L-PIA) was more potent than 5'-N-ethylcarboxamideadenosine (NECA) in mimicking this adenosine effect. By contrast, adenosine enhanced the phase II contraction in non-pretreated preparations, as well as the atropine-resistant capsaicin-sensitive part of this contraction. Here, NECA was more potent than L-PIA. Adenosine, NECA, L-PIA and D-PIA also enhanced the atropine-sensitive component of the phase II contraction, as well as the contractile response to exogenous acetylcholine or carbachol, but not to exogenous substance P. In this respect, L-PIA was the most powerful adenosine analogue with at least 10 fold higher potency than D-PIA. The adenosine antagonist 8-p-sulphophenyltheophylline enhanced the phase I contraction and decreased the capsaicin-sensitive non-adrenergic non-cholinergic component of the phase II contraction. We conclude that adenosine inhibited the nerve-induced cholinergic twitch (phase I) responses by action at prejunctional A1-receptors. Furthermore, adenosine enhanced the phase II contractile responses via postjunctional enhancement of the cholinergic transmission by action at A1-receptors, and via enhancement of the non-adrenergic non-cholinergic transmission by action at presumably prejunctional A2 receptors.
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PMID:Adenosine-modulation of cholinergic and non-adrenergic non-cholinergic neurotransmission in the rabbit iris sphincter. 301 Nov 72

We have previously found that the coronary dilator response to infused adenosine is attenuated in diabetic (alloxan) lambs. Adenosine responsiveness is restored by administration of insulin. The present studies tested the hypothesis that coronary flow changes with hypoxia, if mediated by adenosine, would also be modified. Studies were carried out in eight control and six diabetic lambs. The animals were anesthetized and prepared to maintain constant arterial pressure (reservoir), cardiac output (pump), and heart rate (paced). Atropine and practolol were given. Forced inspired oxygen was reduced in steps. Arterial and coronary sinus blood samples were analyzed for Po2, oxygen content, pH, hematocrit, and glucose. Myocardial oxygen delivery and uptake (MVO2) were calculated. Coronary flow increased identically in both control and diabetic animals as PaO2 was reduced below 60 Torr. Oxygen delivery and MVO2 fell equally in both groups. Acidosis potentiated hypoxic coronary flow changes. Alpha blockade (phentolamine) was without effect in control lambs but caused coronary flow to increase in diabetic lambs. Changes in coronary flow with hypoxia were unaffected, however. Insulin caused no change in the coronary dilator response to hypoxia in either control or diabetic lambs. It is concluded that coronary alpha tone is increased in diabetes but does not modify changes in coronary flow during hypoxia. As coronary flow responses to hypoxia were unaltered in diabetic lambs, and unaffected by insulin, adenosine may not be the primary mediator of coronary vascular dilatation. Potentiation of adenosine by tissue acidosis is apparently insufficient to explain these findings. The mechanism for coronary dilatation during hypoxia is unclear but may involve direct effects of reduced oxygenation of coronary vascular smooth muscle.
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PMID:Coronary vascular responses to hypoxia in the diabetic lamb: independence from adenosine and autonomic mechanisms. 301 81

The possibilities of participation of adenosine in the peristaltic reflex of guinea pig ileum was studied pharmacologically and histologically. Adenosine apparently depressed the peristaltic activity induced by elevation of intraluminal pressure from zero to 1-8 cm H2O, and the extent of the depression somewhat decreased in proportion to the elevation in intraluminal pressure. Also, dipyridamole depressed the peristaltic activity by itself; however, the extent of the depression significantly increased in proportion to the elevation in intraluminal pressure. On the other hand, in the presence of dipyridamole, the elevation of the intraluminal pressure from zero to 1-8 cm H2O elicited an 3H-output increase from 3H-adenosine preloaded guinea pig isolated ileum, with the effect being more pronounced as the pressure was increased. In contrast, the peristaltic activity was more pronounced at lower pressurization. Atropine greatly depressed the peristaltic response but did not affect 3H-output induced by 4 cm H2O pressurization. Tetrodotoxin depressed both markedly. Fluorescence histochemical localization of quinacrine, which binds to adenosin triphosphate (ATP), revealed dense nerve cell bodies and fine interconnecting strands in the ileal myenteric plexus of Auerbach. Also, in microradioautographs of ileal longitudinal muscle incubated with 3H-adenosine, the concentration of developed silver grains was localized in the ganglion cells and in the musculature as varicose fibre. From these results, evidence is provided that the peristalsis of guinea pig ileum may be physiologically modulated by endogenous adenosine, which may be released from neuronal elements of the myenteric plexus in response to the applied intraluminal pressure.
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PMID:Possibilities for adenosine modulation of peristaltic reflex in guinea pig isolated ileum. 409 42

The ionic mechanism underlying the hyperpolarizing action of adenosine and adenine nucleotides was studied by measuring the efflux of 43K or 86Rb from sinus venosus and interauricular septum of tortoise heart. Preparations rendered quiescent by high-K (27 mM) Ringer solution were used. Adenosine and ATP increased the efflux of 43K and 86Rb from sinus venosus. The magnitude of the responses varied from preparation to preparation, but in the same tissue adenosine and ATP were of equal efficacy. When dose-response relationships could be determined, the adenyl compounds were found to be of similar potency. Km for adenosine was 6.2 X 10(-6) M, for ATP 8.3 X 10(-6) M. Regional variations in the magnitude of the responses were observed. The largest responses were obtained from the muscular strip of sinus venosus near its junction with atrium, and from the right horn of the sinus venosus. In interauricular septum the adenyl compounds caused only a slight increase in isotope efflux. Acetylcholine, by contrast, produced large increases in 86Rb efflux from all these preparations. Thus the distribution of the purinoceptors in the tortoise heart is more confined than that of the muscarinic receptors. Antagonism of the response to adenyl compounds by theophylline and 8-phenyltheophylline was studied. The apparent Ki for theophylline was 10(-5) M; that for 8-phenyltheophylline about 10(-6) M. Atropine did not inhibit the responses to the adenyl compounds. These results indicate that the changes in K permeability produced by adenosine and ATP are mediated by P1-purinoceptors. The adenosine transport inhibitors, dipyridamole and nitrobenzylthioinosine (NBMPR), had no effect on the adenyl-induced responses, indicating that adenosine uptake is of little importance in tortoise sinus venosus. The effects of phosphate-modified ATP analogues were studied. Adenylimidodiphosphate (APPNP) produced increases in 86Rb efflux similar to those found with ATP, confirming that breakdown of ATP to adenosine is not obligatory for its action at P1-purinoceptors. Alpha-beta methylene ATP (APCPP) and beta-gamma methylene ATP (APPCP) produced much smaller effects, which may be explained by their structural and chemical differences from ATP. The use of 86Rb as a tracer (Rb: K less than 0.01 in load solution) gives qualitatively similar results to those obtained when 43K is used to study the permeability increases produced by the adenyl compounds or acetylcholine. Quantitative differences in the measures obtained with the two isotopes, however, become apparent when the efflux of both is studied simultaneously.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Ionic basis of the hyperpolarizing action of adenyl compounds on sinus venosus of the tortoise heart. 609 Jun 38

The effects of adenyl compounds were examined on dogfish atria and ventricles. Adenosine, ATP, beta, gamma-methylene ATP ( APPCP ) and 2-chloroadenosine produced negative inotropic and chronotropic effects on the dogfish atrium, which were antagonized by 8-phenyltheophylline, a P1- purinoceptor antagonist. alpha-beta-Methylene ATP ( APCPP ), which is resistant to degradation, did not produce a similar inhibitory response in the dogfish atrium. Atropine did not affect the responses to adenosine, indicating that adenosine did not produce its effects indirectly by the release of acetylcholine. The effects of adenosine and ATP were not potentiated by dipyridamole, which blocks adenosine uptake; and 2-chloroadenosine, which is reported to be resistant to uptake and deamination, was equipotent with adenosine; this suggests the absence of an adenosine uptake system. Dogfish ventricles were insensitive to adenyl compounds. Adrenaline, noradrenaline and acetylcholine produced positive inotropic effects on the ventricle. It is concluded that inhibitory P1- purinoceptors are present in the dogfish atrium. However, adenyl compounds had no direct action on the contractility of the dogfish ventricle.
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PMID:The effect of adenyl compounds on the heart of the dogfish, Scyliorhinus canicula. 614 31

In the isolated rabbit papillary muscle, adenosine (1-300 microM) alone scarcely affected the basal tension developed. The positive inotropic action of isoprenaline, mediated via beta-adrenoceptors, was inhibited by adenosine in a concentration-dependent manner. Atropine (0.3 microM) abolish the inhibitory action of carbachol on the isoprenaline-induced positive inotropic action but not affect the inhibitory asction of adenosine. Adenosine failed to inhibit the positive inotropic action exerted by phenylephrine via stimulation of alpha-adrenoceptors in the presence of pindolol (30 nM). The present results indicate that the positive inotropic action was mediated via alpha-adrenoceptors whose subecllular mechanism was not susceptible to the inhibitory action of adenosine as are beta-adrenoceptors.
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PMID:Adenosine antagonizes the positive inotropic action mediated via beta-, but not alpha-adrenoceptors in the rabbit papillary muscle. 625 Aug 59

1 Drug actions on electrical and mechanical properties of smooth muscle cells and neuromuscular transmission in the canine cerebral arteries were investigated by use of microelectrode and isometric tension recording methods. 2 In the basilar and middle cerebral arteries, the resting membrane potentials were--49.4 mV and -51.7 mV, respectively, the length constants 0.57 mm and 0.45 mm, respectively and the time constants 142 ms and 118 ms, respectively. 3 Outward current pulses did not evoke the spike in either artery but did evoke the spike under conditions of pretreatment with 10 mM tetraethylammonium (TEA). 4 The maximum slope of depolarization produced by a ten fold increase in [K]o plotted on a log scale was 40.1 mV in the basilar artery and 42.2 mV in the middle cerebral artery. 2-Nicotinamidoethyl nitrate, the K-permeability accelerator, had no effect on the membrane potential. 5 K-free or ouabain [10(-5)M] treatment slightly depolarized the membrane. Re-addition of K [5.9 mM] hyperpolarized the membrane by several mV. Thus, the contribution of an active Na-K pump in the membrane potential seems to be small. 6 In both arteries, acetylcholine, adenosine, noradrenaline and isoprenaline in concentrations up to 10(-5)M did not modify the membrane potential and resistance, while 5-hydroxytryptamine (over 10(-8)M) and ATP (over 10(-5)M) depolarized the membrane, decreased the membrane resistance and produced a dose-dependent contraction. Adenosine suppressed the contraction evoked by excess [K]o (39.8 mM). 7 Perivascular nerve stimulation produced excitatory junction potentials (e.j.ps). Often e.j.ps were followed by a hyperpolarization. Repetitive stimulation produced facilitation after several stimuli and depression followed. In some cells, this depression appeared without facilitation. 8 The e.j.ps ceased with pretreatment with guanethidine (10(-6)M) or tetrodotoxin (3 X 10(-7)M), while phentolamine (10(-7)M) and yohimbine (10(-7)M) enhanced the amplitude of e.j.ps. ATP (10(-5)M) and noradrenaline (10(-6)M) suppressed and prazosin had little effect on the e.j.ps. Atropine (10(-6)M) also had no effect on the e.j.ps. 9 Specific features of the cerebral artery and systemic vascular beds were compared, and the features of adrenoceptors on the smooth muscle membrane were compared with findings in other vascular beds.
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PMID:Membrane properties and excitatory neuromuscular transmission in the smooth muscle of dog cerebral arteries. 629 82


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