bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of adenosine‐induced bronchoconstriction: An animal model
Authors: Pauwels Romain , Joos Guy F. , Kips Johan C. , Peleman Renaat A. 
Published: January 2005

AbstractA rat model of adenosine‐induced bronchoconstriction has been used to study the mechanism involved in the adenosine‐induced airway narrowing. A remarkable difference in bronchial responsiveness to adenosine between various inbred rat strains was observed. The BDE strain was the most responsive strain and was used for further characterization of the adenosine response in the airways. Tachyphylaxis to a second challenge was a constant phenomenon. The order of potency of adenosine analogues was 5′N‐ethoxycarboxy‐adenosine (NECA) > adenosine > N6‐(2‐phenylisopropl)‐adenosine (R‐PIA). The adenosine‐induced bronchoconstriction was mainly caused by the activation of mast cells and postganglionic vagal neurons. The direct effect of adenosine of bronchial smooth muscle was rather limited. Adenosine challenge induced the release of histamine and 5‐hydroxytryptamine in the airways. Cromoglycate, nedocromil, theophylline, and enprofylline inhibited the adenosine‐induced bronchoconstriction. Adenosine and neurokinin A had an additive and possibly a synergistic effect in causing bronchoconstriction and mast cell activation. © 1993 Wiley‐Liss, Inc.
Possible role of adenosine receptors in psychiatric diseases
Authors: van Calker Dietrich , Berger Mathias 
Published: January 2005

AbstractEffective antidepressive treatments like electroconvulsive therapy and sleep deprivation increase adenosine A1‐receptors in the brains of experimental animals. It has therefore been of considerable interest that carbamazepine, which is known to be clinically similarly effective as lithium ions in the prophylaxis of affective illness, interacts with adenosine receptors. We have recently characterized this interaction using cellular model systems, in which adenosine receptor subtypes evoke different second messenger responses. The results show that carbamazepine at therapeutically relevant concentrations, is a selective antagonist of the A1‐ but not of the high affinity A2‐receptor subtype. The increase in the frequency and severity of the episodes that is often observed in the course of affective illness has been interpreted as the result of plastic changes in neuronal sensitivity that lead to the development of pathologically supersensitive neural circuits. The prophylactic properties of lithium ions are thought to be due to a dampening of the inositol‐phospholipid second not directly influence the generation of inositol phosphates. However, adenosine‐agonists, presumably acting via A1‐receptors, can potently modulate the neurotransmitter‐evoked increase of inositol phosphates and cytosolic free calcium ions. This effect could play a role in synaptic plasticity. Indeed, A1‐agonists can block the development of “long term potentiation,” a model of synaptic plasticity. We suggest that the prophylactic properties of carbamazepine in affective psychoses might be related to the inhibition by carbamazepine and the subsequent supersensitization of the A1‐receptors that modulate the neurotransmitter‐induced formation of inositol phosphates and synaptic plasticity. © 1993 Wiley‐Liss, Inc.
Adenosine receptors in rat brain synaptosomes: Receptor characterization and relationships with glutamate release
Authors: Dagani Fiorenzo , Cattabeni Flaminio , Canevari Laura , Ferrari Rosaria , Camisa Manuela , Abbracchio Maria P. 
Published: January 2005

AbstractThe role of adenosine receptor(s) activation in modulating glutamate release in synaptosomes isolated from different rat brain areas was investigated. Receptor binding studies with selective A1 and A2 adenosine receptor ligands were performed in parallel with functional studies on depolarization‐induced increases of intrasynaptosomal calcium concentrations and glutamate release. Specific binding to the selective A1 ligand [3H]‐Cyclohexyladenosine was detected, with highest densities in hippocampal synaptosomes, followed by c. striatum and cortex. In contrast, no specific binding to the selective A2a ligand [3]CGS 21680 was demonstrable in synaptosomes from any of the studied brain areas, suggesting that no adenosine receptors belonging to this receptor subtype are present on rat brain pre‐synaptic terminals. In parallel, the adenosine analogue cyclopentyladenosine (CPA) could partially inhibit the KCl‐induced glutamate release from hippocampal synaptosomes. The agonist‐induced effect was monophasic, dose‐dependent, and already demonstrable at the 10−8 M concentration, which indeed confirms that only A1 receptors inhibitory on calcium‐dependent release are functionally present in synaptosomal preparations. The effect on glutamate release was likely due to the ability of CPA to partially counteract KCl‐induced increases of intrasynaptosomal calcium concentrations. IT is therefore concluded that rat hippocampal synaptosomes represent an adequate in vitro model to study the molecular and functional correlates of pre‐synaptic adenosine receptors, and therefore investigate their role in both physiological and ischemia‐associated pathological neurotransmission. © 1993 Wiley‐Liss, Inc.
Guanine nucleoside diphosphate and triphosphate modulate [3H]CGS 21680 binding to A2 adenosine receptor in rat striatal membranes
Authors: Mazzoni Maria R. , Tacchi Paolo , Martini Claudia , Lucacchini Antonio 
Published: January 2005

AbstractIn striatum and several other tissue, a guanine nucleotide binding protein (Gs) couples A2 adenosine receptor to activation of adenylyl cyclase. We have examined the effect of guanine nucleoside diphosphate and triphosphate on [3H]CGS 21680 binding to A2A adenosine receptors of rat striatum. Both GDP and GTP inhibited specific [3H]CGS 21680 binding to rat striatal membranes by 50% at about 0.1 mM. GMP was inhibitory only at higher concentrations, and the estimated IC50 value was greater than 1mM. The nonhydrolyzable analog of GTP, GPP (NH)p, was as potent as GTP with an IC50 value of approximately 86 μM. These results suggest that the regulation of A2a adenosine receptor binding properties by guanine nucleotides is independent of Gs activation, since inhibition of agonist binding is achieved by addition of agonist binding is achieved by addition of both guanine nucleoside diphosphate and triphosphate © 1993 Wiley‐Liss, Inc.
Antagonistic A2a/D2 receptor interactions in the striatum as a basis for adenosine/dopamine interactions in the central nervous system
Authors: Fuxe Kjell , Ferré Sergi , Snaprud Per , von Euler Gabriel , Johansson Björn , Ferdholm Bertil 
Published: January 2005

AbstractFrom behavioural and biochemical experiments, we have found evidence for the existence of a specific adenosine A2a receptor/dopamine D2 receptor interaction in the brain. Behavioural data show that stimulation A2a receptors inhibits and their blockade potentiates a D2‐mediated locomotor activation in mice and that stimulation of D2 receptors counteracts on A2a mediated cataleptic effect in rats. Biochemical data show that, in rat striatal membrane preparations, A2a receptor stimulation decreases the affinity of D2 receptors and the transduction of the signal from the D2 receptor to the G‐protein. Based on these findings it is postulated that this A2a/D2 interaction might be the main mechanism responsible for the central effects of adenosine agonists and antagonists, like methylxanthines. The increased behavioural effect of methylxanthines after dopamine denervation could be explained by an increased interaction between adenosine A2a and dopamine D2 receptors. Membrane preparations‐denervated striatum are more sensitive to the effect of adenosine A2a receptor stimulation. Our results underline the potential antiparkinsonian action of adenosine A2a antagonists and the potential antipsychotic of adenosine A2a agonists. © 1993 Wiley‐Liss, Inc.
Extracellular adenosine, formed during low level NMDA receptor activation, provides an inhibitory threshold against further NMDA receptor‐midiated neurotransmission in the cortex
Authors: White Thomas D. , Craig Constance G. , Hoehn Katja 
Published: January 2005

AbstractIn the cortex only a few of the available NMDA receptors must be activated to evoke maximal release of adenosine. In fact, maximal adenosine release occurs at 30 μM NMDA, a concentration at which noradrenaline release is only 20% maximal. NMDA‐evoked noradrenaline release appears to require the generation of propagated action potentials, while adenosine release does not. Noncompetitive block of NMDA‐evoked release of adenosine, but not noradrenaline, can be overcome by increasing NMDA concentrations. The above findings are consistent with the possibility that there are spare receptors for NMDA‐evoked adenosine release, but not for nor‐adrenaline release. These spare receptors are not due to elevated levels of glycine in the vicinity of those NMDA receptors mediating adenosine release. Functionally, it appears that low level NMDA receptor activation provides a purinergic inhibitory threshold against higher level NMDA receptor mediated processes. This could provide inhibitory tone and selectivity for critical functions, such as learning, memory, and synaptic plasticity in the cortex. © 1993 Wiley‐Liss, Inc.
Intracoronary diltiazem limits infarct size during prolonged angioplasty balloon inflation
Authors: Rose Gregory C. , Jordan Joey C. , Jolly Stanley R. 
Published: January 2005

AbstractAn animal model of failed coronary angioplasty was used to evaluate the effect of intracoronary diltiazem on regional ischemia and the degree of myocardial necrosis. Ischemia was produced in closed‐chest, pentobarbital‐anesthetized male mongrel dogs by inflation of 2.5–3.0 mm diameter balloons introduced under fluoroscopy into the left anterior descending or left circumflex coronary arteries. Animals were randomly assigned to control or diltiazem administered at the time of balloon inflation. Diltiazem, 900 μg/kg, was administered in divided doses through the lumen of the angioplasty balloon catheter. Diltiazem reduced the mean arterial pressure by 27 ± 6 mm Hg and blunted tachycardia following occlusion, which was also seen in controls. After 50 min of ischemia, a left thoracotomy was performed, and the left atrium was cannulated for injection of radiolabeled microspheres at 70 min. The animal was then reperfused by deflating the balloon. Regional segment function showed similar dyskinesis in the ischemic area of both groups. At 4 h the animal was sacrificed and the heart was removed for measurement of the area at risk and infarct size using a dual staining technique. Infarct size, when determined as the percent of the area at risk, was significantly reduced in diltiazem treated animals, 9 ± 2%, as compared to control animals, 22 ± 5%. Regional myocardial blood flow did not differ between groups. Therefore, intracoronary diltiazem produced a significant reduction in myocardial injury. This intervention may be useful to delay cell death in the setting of failed coronary angioplasty. © Wiley‐Liss, Inc.
Comparison of the cardiovascular effects of the α2‐adrenoceptor agonist, dexmedetomidine, in rats and rabbits
Authors: MacDonald Ewen , Vartiainen Jaana , Jäsberg Kari , Urtti Arto 
Published: January 2005

AbstractDexmedetomidine is a potent, specific, and selective α2‐adrenoceptor agonist undergoing clinical trials as an adjunct to anesthesia. It may also have potential use in the treatment of glaucoma. In anesthetized rats and rabbits, dexmedetomidine induced marked bradycardia, rats being 5 times more sensitive than rabbits. In conscious rabbits, the bradycardia induced by dexmedetomidine was even less apparent; a dose of 40 αg/kg ws needed to consistently slow the pulse. Higher doses of dexmedetomidine induce a direct vasoconstrictor response in the anesthetized animals, in the case rabbits were 9 times less sensitive than rats. In both tests the anesthetized rat better mimicked the sensitivity of humans to dexmedetomidine. Thus, it should be remembered that in ocular pharmacology, where the rabbit is the prevalent experimental animal used, this species is relatively insensitive to the cardiovascular effects of this novel α2‐adrenoceptor agonist. © Wiley‐Liss, Inc.
Effects of S 9977 on learning and memory in the mouse and rat
Authors: File Sandra E. , Mabbutt Peter S. , Bontempi Bruno , Destrade Claude , Jaffard Robert 
Published: January 2005

AbstractS 9977 (1,3,7‐trimethyl 8‐[3‐(4‐diethylaminocarbonyl‐l‐piperazinyl)1‐propyl]‐3,7‐dihydro(1H)2,6‐purinedione hydrochloride) is a methylxanthine derivative lacking activity at adenosine receptors and having no phosphodiesterase inhibitory action, but which has been reported to enhance cholinergic function. In mice 0.06 mg/kg ip increased, whereas 0.25 and 1 mg/kg ip decreased, spontaneous alternation in a T‐maze. Doses of 0.03 and 0.06 mg/kg ip improved acquisition and retention of a spatial discrimination task when administered on the test days. The dose of 0.06 mg/kg ip was without effect on subsequent retention when given immediately post‐acquisition, suggesting it was without effect on storage processes. When it was administered for 14 days prior to testing 0.06 mg/kg ip retained its effects on acquisition and retention of the discrimination task, but no longer had significant effects on spontaneous alternation. In rats, there was no effect on between‐day habituation of exploration or on acquisition of a working and reference memory task with a 24 h intertrial interval. However, 0.06 mg/kg ip significantly improved retention of this task and 0.12 mg/kg ip significantly improved acquisition when a 48‐h intertrial interval was used, mainly due to a reduction in working memory errors. In a test of reference memory in a helical maze 0.03 mg/kg ip improved acquisition. These results suggest that low, but not high, doses of S 9977 can improve acquisition in tasks relying on both working and reference memory and also can improve performance on retention tasks. The results are discussed with reference to the effects of S 9977 in enhancing cholinergic function. © Wiley‐Liss, Inc.
Paradoxical effects of 2‐amino‐4‐phosphonobutanoic acid and other 2‐amino‐ω‐phosphonoalkanoic acid on the n‐methyl‐d‐aspartate receptor ion channel
Authors: Szabó Géza , Horváth Edit J. , Aráanyi Péter 
Published: January 2005

AbstractAn extensively washed membrane preparation was used to measure the noncompetitive binding site of the N‐methyl‐D‐aspartate (NMDA) receptor complex with [3H]‐1‐[1‐(2‐thienyl) cyclo‐hexyl] piperidine ([3H]‐TCP). Addition of glutamic acid (Glu) or Glu + glycine (Gly) increased the binding of [3H]‐TCP, reflecting that the NMDA receptor ion channel was opened by these compounds. [3H]‐TCP binding was also increased by various 2‐amino‐ω‐phosphonoalkanoic (AP) compounds, of which 2‐amino‐4‐phosphonobutanoic acid (AP4) was the most effective. The effects of AP compounds were also observed in the presence of Gul. However, in the presence of Gly, or in the presence of Glu + Gly, 2‐amino‐5‐phosphonopentanoic acid (AP5) and 2‐amino‐7‐phosphonoheptanoic acid (AP7) inhibited the binding. The enhancing effect of AP4 was also inhibited by these compounds. Our conclusion is that AP compounds exert complex effects: they bind to and effect the NMDA receptor complex ion channel not only via the competitive binding site but may also interact with the potentiating Gly binding site. © Wiley‐Liss, Inc.
Effects of BMY 33462, a selective and potent serotonin type‐3 receptor antagonist, on mesolimbic dopamine‐mediated behavior
Authors: Geissler Marie A. , Torrente John R. , Eison Arlene S. , Gylys Jonas A. , Wright Robert N. , Iben Lawrence G. , Davis Houston H. , Yocca Frank D. 
Published: January 2005

AbstractThe compound BMY 33462 (4‐amino‐N‐(1‐azabicyclo‐[2,2,2]oct‐3‐yl)‐2‐(butan‐2‐one‐3‐yl)oxy‐5‐chlorobenzamine 1.25 fumerate hydrate) has been shown to be a selective and potent serotonin type‐3 (5‐HT3) receptor antagonist. Its receptor binding profile includes subnanomolar affinity for the 5‐HT3 receptor (Ki, 0.22 ± 0.06 nM) and no affinity for other serotonergic, dopaminergic, and adrenergic receptors (Ki > 1,000 nM). BMY 33462 was also shown to be a potent inhibitor of the Bezold‐Jarisch reflex in the anesthetized rat (ED50, 0.09 μg/kg, iv), a functional correlate of 5‐HT3 receptor antagonism in vivo. It has been reported that ondansetron and other 5‐HT3 antagonists have the ability to block hyperactivity in rats induced by DiMe‐C7 ([pGlu5, Me‐Phe8, Sar9]SP5–11), a metabolically stable analogue of substance P [Hagan et al. (1990): Br J Pharmacol 99:227–232]. DiMe‐C7‐induced hyperactivity is thought to occur through activation of mesolimbic dopamine (DA) neurons which project to the nucleus accumbens [West and Michael (1991): Brain Res Bull 26:229–233]. BMY 33462 was examined for its ability to block DiMe‐C7‐induced hyperactivity as was haloperiodol and ondansetron. The dopamine‐2 (D2) antagonist haloperidol produced the greatest inhibition of DiMe‐C7‐induced hyperactivity at a dose of 0.025 mg/kg (53.7%). Ondansetron significantly inhibited the DiMe‐C7‐induced increase in locomotor activity at doses of 0.10 mg/kg and 0.50 mg/kg (42% and 30%, respectively). BMY 33462, at doses of 0.025 mg/kg and 0.05 mg/kg, significantly decreased DiMe‐C7‐induced hyperactivity by 41% and 37%, respectively. Haloperidol proved to be highly efficacious and potent in blocking increases in DiMe‐C7‐induced locomotor activity, a phenomenon which may correlate with its clinical effectiveness as a neuroleptic agent. BMY 33462 and ondansetron were equally efficacious, however, BMY 33462 was more potent. The ability of 5‐HT3 antagonists to alter a mesolimbic DA‐mediated behavior indicates a complex interaction between these two neurotransmitter systems and perhaps a role for central 5‐HT3 receptors and 5‐HT in the regulation of DA transmission. In addition, BMY 33462 and ondansetron were unable to inhibit stereotypy induced by apomorphine (inactive at 100 mg/kg, orally) suggesting a lack of interaction with the nigrostriatal DA pathway. These results support the notion that 5‐HT3 antagonists may be potential therapeutic agents for the treatment of hyperdopaminergic disease states, such as schizophrenia, without the side effect liability generally associated with classical neuroleptics. © 1993 Wiley‐Liss, Inc.
Role of serine/threonine kinase casein kinase‐II in vascular smooth muscle cell proliferation and inhibition by heparin
Authors: Singh Jai Pal , Wiernicki Todd R. , Gupta Shalley K. 
Published: January 2005

AbstractThe role of serine/threonine kinase casein kinase‐II (CK‐II) in vascular smooth muscle cell proliferation and inhibition by heparin was investigated. cDNAs for α and β subunits of CK‐II form rabbit vascular smooth muscle cells were cloned and sequenced. A strong evolutionary conservation was found at amino acid and nucleotide levels in CK‐II from rabbit and human. Treatment of smooth muscle cells with a specific antisense oligonucleotide to CK‐II blocked stimulation of DNA synthesis in response to PDGF. Addition of a known inhibitor of CK‐II to cultures of smooth muscle cells also blocked DNA synthesis. Mitogenic stimulation of growth arrested quiescent cultures of smooth muscle cells with PDGF produced a 2–3‐fold increase in CK‐II activity. Heparin was a potent inhibitor of smooth muscle cell derived CK‐II in vitro and attenuated the stimulation of CK‐II activity in response to PDGF in intact cells. Intracellular localization studies showed that heparin and CK‐II were localized in the nucleus. These results suggest a potential role of CK‐II in signal transduction mediating smooth muscle cell growth. Modulation of CK‐II activity by heparin and its co‐localization in the nucleus suggest that heparin may effect CK‐II activity in intact cells. © 1993 Wiley‐Liss, Inc.
Zatosetron, a selective 5‐HT3 receptor antagonist: Pharmacological activities of human and animal metabolites
Authors: Cohen Marlene L. , Bloomquist William , Schmid Christopher R. , Robertson David W. , Wong David T. 
Published: January 2005

AbstractZatosetron is a potent, orally active 5‐HT3 receptor antagonist with a long duration of activity in laboratory animals and humans. Several metabolites have been detected in plasma and urine of humans and experimental animals receiving zatosetron. The present study was designed to explore the pharmacological activity of the detected metabolites, 3‐hydroxyzatosetron, 3‐ketozatosetron, and N‐desmethylzatosetron, relative to the parent molecule. These three metabolites had relatively high affinity at 5‐HT3 receptors based on in vitro radioligand binding and inhibited serotonin‐induced bradycardia in urethane‐anesthetized rats after intravenous administration. However, these metabolites had lower affinity and were less potent than zatosetron. Of these metabolites, 3‐hydroxyzatosetron (ED50 = 4.0 μg/kg iv) was approximately 5‐fold less potent than zatosetron (ED50 = 0.8 μg/kg iv) in vivo and had approximately 10‐fold lower affinity at 5‐HT3 receptors in vitro relative to zatosetron. N‐desmethylzatosetron and 3‐ketozatosetron were approximately 15‐fold less potent than zatosetron in vivo as 5‐HT3 receptor antagonists. With regard to duration of activity in vivo, after intravenous administration, 3‐hydroxyzatosetron and 3‐ketozatosetron blocked 5‐HT3 receptors longer than zatosetron, whereas N‐desmethylzatosetron showed a duration of pharmacological activity similar to zatosetron. A fourth metabolite, zatosetron‐N‐oxide can exist in two isomeric forms, with stereoselective N‐oxidation of zatosetron resulting in formation of only one isomer in humans, zatosetron‐β‐N‐oxide. Zatosetron‐β‐N‐oxide had approximately 100‐fold lower 5‐HT3 receptor affinity relative to zatosetron and was approximately 150‐fold less active as an antagonist at 5‐HT3 receptors in vivo (ED50 = 115 μg/kg iv). Thus, although pharmacological activity was observed with all four metabolites, they were all less active in vivo than zatosetron. Therefore, these metabolites would contribute significantly to the activity of zatosetron only if plasma (and tissue) levels greatly exceeded those of zatosetron. © 1993 Wiley‐Liss, Inc.
Chronic theophylline prolongs the refractory period in amygdala‐kindled rats
Authors: Kleinsorge Robert J. , Bowers Lakeisha M. , Jarvis Michael F. , Berman Robert F. 
Published: January 2005

AbstractThe effects of chronic theophylline treatment on brain adenosine A1 receptors and amygdala‐kindled seizures were examined in rats. The repeated administration of theophylline 417 μmoles/kg/day i.p. (75 mg/kg/day) for 14 days resulted in a significant increase in 1 nM [3H]cyclohexyladenosine binding to adenosine A1 receptors in thalamus, hippocampus, and cerebellum. This chronic theophylline treatment was shown to significantly prolong the immediate postseizure refractory period (defined as sensitivity to a subsequent kindling stimulation) while both the severity and duration of an initial kindled seizure was not affected. These findings indicate that the postseizure refractory period can be influenced by the brain adenosine system, and implicate adenosine as an important neuromodulator of the patterning of seizure episodes. © 1993 Wiley‐Liss, Inc.