bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of BRL38227, salbutamol, and aminophylline, alone and in combination, on plasma potassium and on the heart
Authors: Clapham John C. , Hamilton Thomas C. 
Published: January 2005

AbstractThe present study was undertaken in order to examine the effects of the potassium channel activator BRL38227 and of aminophylline on hypokalaemia, cardiac stimulation (increased heart rate and contractility, dQ/dt), and electrocardiogram (ECG) changes induced by the β2‐adrenoceptor agonist, salbutamol in the anaesthetised cat. Salbutamol (1.25 μg.kg−1min−1), but not BRL38227 (0.1–1.0 μg.kg−1 min−1), infusion elicited a marked hypokalaemia (plasma K+ >2.5 mmolliter −1). This dose of salbutamol also elicited an immediate cardiac stimulation which appeared to be maximal and changes in ECG were evident as a reduction in QTc interval (20%) and T‐wave height (80%). Cardiac stimulation following either BRL38227 or aminophylline was more gradual in onset, the maximum response being about 50–80% of the salbutamol effect. No ECG changes were observed in cats receiving BRL38227 whilst T‐wave amplitude was reduced (50–60%) following aminophylline. Combination of salbutamol with aminophylline resulted in a greater degree of hypokalaemia, cardiac stimulation, and T‐wave depression. The salbutamol‐induced reduction in QTc was converted to a slight prolongation after infusion for 75 min. The ECG changes observed were not indicative of arrhythmia. Conversely, BRL38227 had no effect on salbutamol‐induced hypokalaemia, cardiac stimulation, or T‐wave depression, though the degree of QTc interval shortening was reduced. When BRL38227 was administered in conjunction with aminophylline, plasma potassium and QTc were unchanged. Depression of T‐wave amplitude by aminophylline was slightly reduced in the combination group. Effects on heart rate and dQ/dt were similar to those seen for BRL38227 alone. Salbutamol‐induced hypokalaemia was reversed by the nonselective β‐adrenoceptor antagonist, propranolol, but not by the β1‐adrenoceptor selective antagonist, atenolol, confirming a β2‐adrenoceptor selective effect. Cardiac stimulation was reversed by both propranolol and atenolol. In conclusion, salbutamol‐induced hypokalaemia, cardiac stimulation, and ECG changes, as well as the additive effect of aminophylline, were demonstrated in the anaesthetised cat, but were unchanged by BRL38227. Furthermore, combination of BRL38227 with aminophylline did not result in any adverse effects on the parameters measured. Thus, on the basis of these results in the cat, combination of BRL38227 with the bronchodilator drugs, salbutamol or aminophylline, would not be expected to exacerbate the cardiovascular effects of these drugs. © 1992 Wiley‐Liss, Inc.
Diuretic and hypotensive actions of torasemide in hypertensive models of rat
Authors: Uchida Takeshi , Ohtaki Yutaka , Kido Hideaki , Shinyama Hiroshi , Hayashi Kazutaka , Yamanaga Katsumi , Watanabe Masahiro 
Published: January 2005

AbstractThe diuretic and the antihypertensive actions of torasemide were examined in renal and genetic hypertensive rats and compared to the effects of furosemide. Oral administration of torasemide (1 and 3 mg/kg) elicited a dose‐dependent increase in the excretion of urine and electrolytes and elevated the urinary Na/K ratio in both renal and genetic hypertensive rats. Torasemide and furosemide had a similar maximum diuretic effect in the normotensive Wistar rat and the spontaneously hypertensive rat (SHR). However, the diuretic activity of furosemide was weaker in the renal hypertensive rat (RHR). Torasemide showed approximately 30 times greater diuretic potency than furosemide. Torasemide and furosemide demonstrated hypotensive action in hypertensive rat models, but not in the normotensive Wistar rat. Especially in the RHR, torasemide exhibited a more potent hypotensive action than furosemide. These results show that the diuretic and antihypertensive activities of torasemide are effective in various rat models of hypertension, while the diuretic activity of furosemide is weak in certain hypertensive rat models. © 1992 Wiley‐Liss, Inc.
Molecular biology of the 5‐HT1 receptor subfamily
Authors: Hartig Paul R. , Adham Nika , Zgombick John , Weinshank Richard , Branchek Theresa 
Published: January 2005

AbstractFour serotonin receptor clones have now been isolated and characterized. They encode the serotonin 5‐HT1A, 5‐HT1C, 5‐HT1D, and 5‐HT2 receptors. The serotonin 5‐HT1C receptor, which was originally classified as a 5‐HT1 receptor, is now seen to be a member of the 5‐HT2 receptor subfamily. Within the current 5‐HT1 receptor subfamily, the two clones that have been described (5‐HT1A and 5‐HT1D) show similarities in amino acid sequence and function but are not as closely related as might have been expected. The human 5‐HT1D receptor clone, when expressed in mouse fibroblast cells, displays pharmacological binding properties in agreement with human cortical membrane preparations. Sumatriptan, a new antimigraine medication, exhibits an apparent dissociation constant of 3.4 nM at this human receptor site. This represents the highest affinity interaction yet identified for this drug, and suggests that significant species differences may exist in the binding of this compound to 5‐HT1D receptors. Similar species differences in ergot drug affinities have been described for the 5‐HT2 receptor. Deduced amino acid sequence homologies between serotonin and other monoamine receptor clones are discussed, leading to a classification scheme for serotonin receptors involving superfamily, family, and subfamily relationships. © 1992 Wiley‐Liss, Inc.
Novel high‐affinity 3H‐serotonin binding sites in rat and bovine brain tissue
Authors: Weisberg Ellen , Teitler Milt 
Published: January 2005

AbstractFive sites (5HT1A, 5HT1B, 5HT1C, 5HT1D, and 5HT1E) have been detected using 3H‐5HT radioligand methodology and mammalian brain tissue. We report herein that high‐affinity 3H‐5HT binding to homogenates of bovine and rat caudate and cortical tissues cannot be interpreted without including at least one additional 5HT receptor. Competition studies were performed in rat frontal cortex tissues, using pharmacological blockade of 5HT1A, 5HT1B, and 5HT1C receptors to facilitate examination of other possible sites. Ergotamine, under these conditions, produced a low‐affinity competition K1 = 1.2 1μM with a Hill coefficient of 1.0. 5‐carboxyamidotryptamine (5CT), under these conditions, produced a complex competition curve, with an overall K1 value of 101 nM and a Hill coefficient of 0.55. Computer‐assisted analysis of the 5CT competition curve revealed a high‐affinity site (K1 = 16nM) and a low‐affinity site (K1 = 802 nM). Therefore, competition curves produced using ergotamine and 5‐CT indicate that there is a site in rat frontal cortical tissue with high affinity for 5HT, 5CT, and low affinity for ergotamine as well as a site with high affinity for 5HT and low affinity for 5CT and ergotamine. The site with high affinity for 5HT, and low affinity for 5CT and ergotamine resembles the 5HT1E receptor, insofar as these three drugs are concerned. There is no reported site with high affinity for 5HT and 5CT and low affinity for ergotamine (heretofore referred to as 5HT1F). The lack of a high‐affinity ergotamine competition for 3H‐5HT binding to non‐5HT1A, 5HT1B, and 5HT1C sites indicates that there is no detectable 5HT1D binding in this tissue. In rat striatal tissue both 5CT and ergotamine produced complex competition curves with Hill coefficients less than unity (0.6 and 0.65, respectively). Computer‐assisted analysis indicated that a minority of sites (approximately 35%) displayed high affinity for both ergotamine and 5CT, while 65% of the sites displayed low affinity for both 5CT and ergotamine. The site labeled with 3H‐5HT displaying high affinity for 5CT and ergotamine coincides with the pharmacological profile of a 5HT1D site. The site labeled with 3H‐5HT displaying low affinity for 5CT and ergotamine coincides with the pharmacological profile of the 5HT1E site. Results from bovine cortical and striatal tissues reinforce the conclusions drawn from the rat brain data. In summary, detailed studies of specific 3H‐5HT binding to non 5HT1A‐1C sites indicate that (1) there are detectable 5HT1D sites in rat striatal tissue but not in rat cortical tissue, (2) there are detectable 5HT1E sites in rat brain tissue, and (c) a novel high‐affinity 3H‐5HT binding site possessing high affinity for 5CT and low affinity for ergotamine has been detected in rat and bovine brain tissues. © 1992 Wiley‐Liss, Inc.
Studies on the effects of 5‐HT1A drugs in the pigeon
Authors: Barrett J. E. 
Published: January 2005

AbstractA number of compounds with high receptor binding affinity for the 5‐hydroxytryptamine (5‐HT) receptor subtype designated as 5‐HT1A can produce anxiolytic and/or antidepressant effects in humans. In contrast to the traditional benzodiazepine anxiolytics, many of the clinically efficacious 5‐HT1A drugs are either ineffective or produce inconsistent results in traditional preclinical anxiolytic screens using behavioral procedures with rodents. In preclinical antidepressant models with these animals, however, effects of the 5‐HT1A drugs, as well as those of traditional antidepressant compounds, are predictive of their antidepressant activity in humans. In contrast, 5‐HT1A drugs are quite effective in pigeons studied under a rather conventional punishment or conflict‐type procedure that is also sensitive to the benzodiazepine anxiolytics. However, traditional antidepressant compounds, such as the tricyclic drugs amitriptyline and imipramine, as well as the 5‐HT reuptake blockers such as fluoxetine, do not show effects similar to the newer 5‐HT1A drugs in this procedure. Thus, in rodents, current antidepressant models are sensitive to drugs that appear to function through different mechanisms, whereas conflict‐type procedures typically do not reveal anxiolytic‐like effects with 5‐HT1A drugs. The pigeon conflict procedure, however, discriminates between the 5‐HT1A antidepressants and antidepressant drugs functioning through other systems, whereas the effects of known anxiolytics in this procedure are quite similar. Increases in punished responding with 5‐HT1A drugs correlates highly (r= +0.83) with affinity for the 5‐HT1A receptor in pigeons. This paper reviews behavioral studies conducted with the pigeon in which the focus has been on the analysis of 5‐HT1A compounds and addresses additional work that is required to answer many of the outstanding questions about this new class of anxiolytic and/or antidepressant drugs. © 1992 Wiley‐Liss, Inc.
Effects of gepirone on ethanol consumption, exploratory behavior, and motor performance in rats
Authors: Knapp Darin J. , Benjamin Dan , Pohorecky Larissa A. 
Published: January 2005

AbstractActivation of 5‐HT receptors via reuptake inhibition, precursor loading, or inhibition of catabolism have consistently resulted in decreases in ethanol preference in rats. The objective of the present studies was to determine whether activation of the 5‐HT1A receptor with gepirone, a selective agonist, decreases ethanol preference. Preference was first evaluated for ethanol solutions from 3 to 11%, in a free‐choice situation with ethanol solution or tapwater available in the home cage. Male Sprague‐Dawley rats consumed the most ethanol solution relative to water at a concentration of 6%. When ethanol (6% solution) was available to ethanol‐habituated rats in a 1‐hr restricted access situation, subjects consumed 5.9 ± 0.4 ml. Pretreatment with gepirone (0.46–4.6 mg/kg IP) resulted in a dose‐dependent reduction in ethanol consumption in the restricted‐access paradigm. The 5‐HT reuptake inhibitor fluoxetine also resulted in dose‐related decreases in ethanol consumption in restricted access. A subsequent experiment using a lower dose of fluoxetine also found a suppressive effect on ethanol intake. A single daily dose of gepirone failed to decrease the consumption of 6% ethanol when it was continuously available in the home cage. The short half‐life of gepirone might explain its lack of effect in continuous access with only one daily dose. Gepirone decreased open‐field activity at higher (2.3 to 4.6‐mg/kg) doses, but did not affect rotorod performance at any dose (4.6–9.2 mg/kg) tested, whereas haloperidol (0.025–1.0 mg/kg) significantly decreased time on the rotorod. These results suggest that 5‐HT1A receptor activation decreases ethanol intake in limited access and that the motorically disrupting effects of gepirone are not manifest under these conditions. © 1992 Wiley‐Liss, Inc.
Gastrointestinal motility responses to the S and R enantiomers of zacopride, a 5‐HT4 agonist and 5‐HT3 antagonist
Authors: Gullikson Gary W. , Virina Maida A. , Loeffler Richard F. , Yang Dai‐Chang , Goldstin Bela , Flynn Daniel L. , Moormann Alan E. 
Published: January 2005

AbstractZacopride is an antiemetic agent whose (S) and (R) stereoisomers demonstrate differential pharmacology at 5‐HT3 receptors, emphasizing the importance of pharmacologic profiling of each enantiomer of a racemic drug mixture. Characterization of the gastrointestinal motility‐enhancing activities of the enantiomers relative to their 5‐HT3 antagonist properties was done both in vivo and in vitro. In dogs at a dose of 0.3 mg/kg, IV, the (S) antipode was more active in stimulating gastric antral contractions and gastric emptying of a solid meal than (R) zacopride. The (S) enantiomer was also at least 10 times more potent in enhancing gastric emptying in rats. The potency of (S) zacopride at the putative prokinetic receptor (5‐HT4) was 3.3 times greater than that of (R) zacopride in rat esophageal tunica muscularis mucosae strips. The greater potency of (S) zacopride over the (R) antipode for motility stimulation was also observed for its 5‐HT3 antagonism in dogs. (S) zacopride almost completely blocked cisplatin emesis at 0.01 mg/kg, IV, while (R) zacopride was inactive. However, both enantiomers were more active as antiemetics than as prokinetics in the dog. More potent activity at the 5‐HT3 than the 5‐HT4 receptor was also demonstrated for both enantiomers in vitro. Additionally, in antagonizing 2‐methyl‐5‐HT contractions in guinea pig ileum, the (S) antipode was again more potent than the (R). In summary, (S) zacopride is more potent than the (R) enantiomer for both 5‐HT3 antagonism and prokinetic activity, with 5‐HT3 antagonism, rather than motility enhancement (5‐HT4 agonism), being the primary activity of both zacopride stereoisomers. © 1992 Wiley‐Liss, Inc.
Free radicals, glutamate, dopamine, and serotonin after ischemia reperfusion insult in aging gerbil brain
Authors: Delbarre R. Bernard , Delbarre Gisèle , Calinon François 
Published: January 2005

AbstractThe study of cerebral ischemia in animals is not easy, because cerebral circulation is not the same as in humans. Indeed, in most animals, there is a collateral circulation between the vertebral and carotid arteries before these arteries enter the brain. On the other hand, in gerbils, unilateral ligation produces ischemia in the ipsilateral forebrain and leads to death in 40–60% of the animals. Because the cerebral ischemia so produced is not effective in all gerbils, it is important to select “sensitive” gerbils by funduscopic examination. Only sensitive gerbils are retained for further experimentation. The nature of the aging process is the subject of some speculation. One hypothesis is referred to as the free radical theory. This theory postulates that free radicals are involved in aging and age‐related disorders of the brain. Therefore, we have determined levels of neuromediators involved in cerebral ischemia and memory, including catecholamines (dopamine [DA], dihydroxyphenylacetic acid [DOPAC], hydroxyvanillic acid [HVA]) and indolamines (5‐hydroxyindolacetic acid [5HIAA], serotonin [5‐HT]), amino acids (aspartate, glutamate and GABA), and free radicals (.OH). We have chosen for study the caudate nucleus, hippocampus, and retina, where changes after ischemia/reperfusion insult are well documented. In gerbil brain, levels of .OH and neurotransmitters are low at birth, reach a plateau, and then decrease with aging. After cerebral ischemia (60 min) induced by left carotid occlusion, the reperfusion (30 min) symptoms are classified using a behavioral score (Stroke Index). Moreover, after ischemia/reperfusion insult (IRI), increases in Stroke Index, .OH, glutamate, aspartate, GABA, monoamines, and indolamines are more pronounced in older gerbils. © 1992 Wiley‐Liss, Inc.
Nicotine suppresses the proliferative response of peripheral blood lymphocytes in rats
Authors: Caggiula Anthony R. , McAllister Cathy G. , Epstein Leonard H. , Antelman Seymour M. , Knopf Steven , Saylor Saundra , Perkins Kenneth A. 
Published: January 2005

AbstractNicotine, the psychoactive ingredient of cigarette smoke, alters lymphocyte function in vitro. However, unlike tobacco smoke, the immunologic effects of nicotine in vivo have not been determined. In the present study a single SC administration of 0.33, 0.66, or 1.32 mg/kg (free base) of nicotine bitartrate to male rats produced a dose‐dependent decrease in the in vitro proliferative response of blood lymphocytes to the T‐cell mitogen Con A when sampled 1 hr after nicotine administration. These results strongly suggest that acute nicotine exposure can induce immune perturbation in vivo. Nicotine also increased plasma corticosterone (CORT) and there was a substantial negative correlation (r = −.52) between CORT levels and the extent of proliferation (DPM) for the optimal Con A dose. The correlation between nicotine's immunologic and CORT effects is discussed within the context of several other potential mediators of nicotine's effects. © 1992 Wiley‐Liss, Inc.
Low molecular weight analogs of trolox with potent antioxidant activity in vitro and in vivo
Authors: Silver Paul J. , Gordon Robert J. , Horan Patrick J. , Bushover Cynthia R. , Gorczyca William P. , Etzler John R. , Buchholz R. Allan , Schlegel Donald , Ellames George J. , Smith David I. , Ezrin Alan M. 
Published: January 2005

AbstractAlpha‐tocopherol and its water‐soluble derivative, Trolox, are capable of terminating free radical chain reactions and limiting reperfusion‐induced cell damage. In the present study, we have quantitated the effects of two relatively potent analogs of alpha‐tocopherol/Trolox, WIN 62079 and U‐78517F, which attenuated exogenously generated free radical damage in cultured cells and reperfusion injury in vivo. In a cultured rat renal tubular epithelial cell line (NRK‐52E), millimolar concentrations of ascorbate or the combination of Trolox plus ascorbate reduced cellular damage (quantitated as lactate dehydrogenase [LDH] release) induced by radicals generated by hypoxanthine/xanthine oxidase. In contrast, WIN 62079 and U‐78517F attenuated damage at micromolar concentrations. Similarly, intravenous administration of WIN 62079 (three hourly doses of 3 mg/kg) and U‐78517F (10 mg/kg infused over 5 min) reduced reperfusion‐induced myocardial damage in rabbit coronary‐occulded hearts: Trolox (three hourly doses of 100 mg/kg) was less potent and required ascorbate (three hourly doses of 150 mg/kg) as a cofactor. These data demonstrate that is feasible to design potent, water‐soluble analogs of Trolox which are efficacious against free radical‐mediated cell death and which do not require ascorbate as a cofactor. Moreover, since U‐78517F and WIN 62079 are two to three orders of magnitude more potent than Trolox, and since they contain different amino side chains, these data further support the concept that side chain modifications of the chromane ring nucleus of alpha‐tocopherol derivatives significantly affect activity, possibly by providing additional activity or by enhancing availability to the cellular site of action. © 1992 Wiley‐Liss, Inc.
Neurokinin A‐induced guinea pig gallbladder contraction: Potential mechanism of action
Authors: Moummi Chafiq 
Published: January 2005

AbstractThe present study was performed to examine the mechanism of action of neurokinin A (NKA) on guinea pig gallbaldder smooth muscle. Muscle strips were prepared and mounted in 10 mL tissue bath containing Krebs' solution under 1 g tension. NKA induced a concentration‐dependent increase in gallbladder muscle tension and reached a maximal response at 1 μM. The EC50 value was approximately 30nM. Preincubation of the muscle strips with neurotoxins, tetrodotoxin (1 μM), or omega‐conotoxin (0.1 μM) had no effect on the NKA contractile response. NKA‐induced gallbladder contractions were insensitive to cyclooxygenase inhibitors (5 μM) piroxicam and indomethacin. In contrast, the calcium channel blockers verapamil and diltiazem (0.1–1 μM) significantly blocked the contractile response to NKA. The intracellular calcium chelator BAPTA/AM had no significant effect on NKA activity. The removal of extracellular calcium, however, completely abolished the contractile response of NKA. These data suggest that NKA has a direct contractile effect on guinea pig gallbladder smooth muscle, which is independent of prostaglandin release. The primary source of calcium involved in mediating the NKA contractile response is the extracellular pool, suggesting that NKA might act via activation of L‐type voltage‐operated calcium channels to mediate its action. © 1992 Wiley‐Liss, Inc.
Protective effects of zinc L‐carnosine (Z‐103) on reserpine‐induced gastric ulceration in rats
Authors: Cho C. H. 
Published: January 2005

AbstractThe present study examined the gastric protective effects of zinc L‐carnosine (Z‐103) in reserpinized rats. We also studied whether this antiulcer effect is related to the preservation of mast cells degranulation in the glandular mucosa. Reserpine administration (5 mg/kg, intraperitoneally [i.p.]) produced severe hemorrhagic glandular ulcers which were accompained with a marked decrease in mucosal mast cell counts. The severity of ulcers and mast cell degranulation were reduced by Z‐103 when given orally 30 min before and 6 hr after reserpinization. However, this protection was not observed when the drug was administered as a single dose 30 min beforehand. The present findings extended the antiulcer action of Z‐103 from stress‐ and ethanol‐induced gastric damage to those on reserpine‐provoked gastric ulcers. It also indicates that the protective action on reserpine ulceration is likely to be due to the stabilization on mast cell membrane in the glandular mucosa. © 1992 Wiley‐Liss, Inc.
Potentiation of atropine‐induced retardation of small intestine transit in mice by a pulsed magnetic field
Authors: Santini R. , Seigne M. 
Published: January 2005

AbstractThe interaction of a pulsed (100 and 50 Hz) magnetic field (90 μT) with the effect of atropine on small intestine transit was studied in mice. Both frequencies of the magnetic field significantly potentiated the atropine‐induced delay in intestinal transit but did not affect intestinal transit per se. This result further strengthens previous observations on interactions between electromagnetic fields and the actions of drugs. © 1992 Wiley‐Liss, Inc.