bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of the calcium channel facilitator, CGP 28,392, on different modes of contraction in smooth muscle of rabbit and rat aortae and guinea‐pig taenia caeci
Authors: Karaki H. , Nagase H. , Ozaki H. , Urakawa N. , Weiss G.B. 
Published: July 2012

Effects of a Ca2+ channel facilitator, CGP 28,392, on smooth muscle contractions were examined in order to delineate characteristics of Ca2+ channels in rabbit and rat aortae and guinea‐pig taenia caeci.
Application of increasing concentrations of KCl induced contractile responses in these smooth muscles and CGP 28,392 shifted the concentration‐response curve for KCl to the left. The maximum response was also increased in rat aorta and guinea‐pig taenia. CGP 28,392 also shifted the concentration‐response curves for noradrenaline in rat aorta and for histamine in taenia to the left and increased the maximum response in rat aorta. However, the corresponding curve for noradrenaline in rabbit aorta was not affected by CGP 28,392.
The sustained contractions induced by KCl were inhibited by cumulative application of verapamil in these smooth muscles. Pretreatment of the muscle with CGP 28,392 decreased the inhibitory effect of verapamil. The noradrenaline‐induced contraction in rat aorta and the histamine‐induced contraction in taenia were also inhibited by verapamil, and CGP 28,392 antagonized the effect of verapamil. The noradrenaline‐induced contraction in rabbit aorta was only slightly inhibited by verapamil, and CGP 28,392 did not modify the effect of verapamil.
In these smooth muscles, cumulative application of Ca2+ to the Ca2+‐depleted, KCl‐treated muscle induced contraction, and the concentration‐response curve for Ca2+ was shifted to the left by CGP 28,392 and to the right by verapamil. The concentration‐response curves for Ca2+ in Ca2+‐depleted, noradrenaline‐treated rabbit and rat aortae and in Ca2+‐depleted, histamine‐treated taenia were also shifted to the left by CGP 28,392 and to the right by verapamil. In some contractions, CGP 28,392 increased and verapamil decreased the maximum responses. CGP 28,392 antagonized the inhibitory effect of verapamil.
These results suggest that the Ca2+ channel facilitator, CGP 28,392, has a relatively selective activating effect on voltage‐dependent Ca2+ channels in rabbit aorta. However, it also activates receptor‐linked Ca2+ channels in rabbit aorta when Ca2+ concentrations are low. In rat aorta and guinea‐pig taenia this facilitator activates both types of Ca2+ channels.
The selectivity of the (−)‐and (+)‐forms of hyoscine methiodide and of hyoscyamine camphorsulphonate for muscarinic (M2) receptors
Authors: Barlow R.B. , Dawson Sally 
Published: July 2012

The affinities of (−)‐S‐hyoscyamine (+)‐camphorsulphonate, (+)‐R‐hyoscyamine (−)‐camphorsulphonate, (−)‐S‐hyoscine methiodide and (+)‐R‐hyoscine methiodide for muscarinic acetylcholine receptors in guinea‐pig atria and ileum at 30°C and in ileum at 37°C have been measured in dose‐ratio experiments. The agonists were carbachol, arecaidine propargyl ester (APE) and ethoxyethyl trimethylammonium iodide (EOE).
The effects produced by the agonists confirmed that, relative to carbachol, arecaidine propargyl ester is more active on atria than on ileum whereas ethoxyethyl trimethylammonium iodide is more active on ileum than on atria.
There was no striking difference between estimates of affinity based on the effects of agonists on atrial size and the effects on atrial rate nor was there any striking difference between the affinities measured with the different agonists.
With the isomers of hyoscyamine there was no striking difference between the affinity for receptors in atria and those in ileum, which is consistent with the low selectivity reported for atropine (racemic hyoscyamine). (−)‐S‐Hyoscine methiodide had greater affinity for muscarinic receptors in ileum than for those in atria, though the difference is smaller than has been previously observed. (+)‐R‐Hyoscine methiodide had no detectable selectivity. The phenomenon of selectivity cannot be wholly ascribed to differences in physicochemical properties of the antagonists: the three‐dimensional structures with which the antagonists interact cannot be identical.
Inotropic effects of Ca2+ channel agonist and antagonists in neuraminidase‐treated left atria of rats
Authors: Hattori Yuichi , Hazama Setsuro , Kanno Mono , Nakao Yasuo 
Published: July 2012

The effects of removal of sialic acid from cardiac sarcolemma on contractile functions and on inotropic responses to Ca2+ channel agonist and antagonists were investigated in rat left atria.
About 64% of the total sialic acid content of the left atria was removed during a 90 min exposure to neuraminidase (2 u ml−1).
The removal of sialic acid neither affected the development of twitch tension induced by stimulation at a frequency of 0.5 Hz, nor altered the interval‐dependent changes in contractility such as the force‐frequency relationship and post rest contractions.
The positive inotropic effects produced by isoprenaline, and by an increase in extracellular Ca2+ concentration were the same in the neuraminidase‐treated preparations as those in the untreated preparations. Bay K 8644, a Ca2+ channel agonist, induced an increase in conractility in the neuraminidase‐treated preparations comparable to that in the untreated ones.
Neuraminidase treatment significantly attenuated the negative inotropic effects of verapamil and diltiazem, whereas it had no effect on that of nifedipine.
The results indicate that sialic acid removal modifies neither the basal contractile functions nor the positive inotropism which is associated with an enhancement of the slow inward Ca2+ current. However, sialic acid, which constitutes the glycocalyx of the cardiac sarcolemma, may be involved in the mechanism of the Ca2+ channel antagonistic actions of verapamil and diltiazem, but not that of nifedipine. Thus, our results provide pharmacological evidence that verapamil and diltiazem behave differently from the dihydropyridine compounds.
The effects of thyroxine treatment of rats on neuronal and extraneuronal uptake and metabolism of catecholamines in the heart
Authors: Bryan Lesley J. , O'Donnell Stella R. , Williams Adrienne M. 
Published: July 2012

The effects of thyroxine (T4) treatment of rats on the neuronal and extraneuronal uptake and subsequent metabolism of catecholamines in the heart were examined, to determine whether changes in the local dissipation of catecholamines might contribute to the enhanced sympathetic cardiac responses that occur when thyroid hormone levels are elevated.
T4‐treated rats were injected subcutaneously with L‐thyroxine sodium 1 mg kg−1 on days 1, 3 and 5, and controls were injected with the normal saline vehicle on the same days. The experiments on isolated, perfused hearts were carried out on day 8. The T4‐treated rats had only 50% of the growth rate of the controls and their heart weights were 18% greater than the controls. The experimental data were adjusted to allow for the increase in heart weight caused by the T4 treatment.
The initial rates of neuronal uptake of noradrenaline and of extraneuronal uptake of noradrenaline and isoprenaline in the hearts from T4‐treated rats were not significantly different from those in hearts from control rats.
The steady‐state rates of extraneuronal O‐methylation of isoprenaline and of extraneuronal deamination of noradrenaline in hearts from T4‐treated rats were not significantly different from those in hearts from control rats.
The steady‐state rate of neuronal deamination of noradrenaline was significantly lower and the accumulation of unmetabolized noradrenaline in the hearts was significantly greater in T4‐treated rats than in the controls. These findings could be explained by a decrease in neuronal monoamine oxidase activity or by an increase in intraneuronal binding of noradrenaline in hearts from T4‐treated rats. If the first of these two speculations should be correct, the changes in neuronal dissipation could contribute to cardiac supersensitivity to noradrenaline or adrenaline, since these amines are substrates for neuronal uptake. However, it could not explain cardiac supersensitivity to isoprenaline in T4‐treated rats.
The study has shown that it is unlikely that increased plasma thyroid hormone levels cause cardiac supersensitivity to catecholamines by affecting the local dissipation processes for those amines in the heart.
B‐HT 958 lowers blood pressure and heart rate in the rat through stimulation of dopamine receptors
Authors: Brown Morris J. , Harland Deborah 
Published: July 2012

To investigate whether the hypotensive and bradycardiac effects of B‐HT 958 (2‐amino‐6‐(p‐chlorobenzyl)‐4H‐5,6,7,8‐tetrahydrothiazolo‐(5,4‐d) azepine) are due to the stimulation of peripheral prejunctional α2‐adrenoceptors, the selective α2‐adrenoceptor antagonist idazoxan was given either intravenously (i.v.) or intracerebroventricularly (i.c.v.) to anaesthetized rats before the administration of i.v. B‐HT 958. Plasma noradrenaline was used as an approximate index of peripheral sympathetic nervous activity.
B‐HT 958 350 μg kg−1 i.v. caused significant falls in blood pressure and heart rate which were maximal 5 min after dosing (− 29.25 ± 3.2 mmHg and − 52 ± 6.8 beats min−1 respectively, mean of all control animals). The hypotension and bradycardia were accompanied by significant falls in plasma noradrenaline concentration of 30–40%.
Idazoxan 300 μg kg−1 i.v. caused a marked, but transient tachycardia and a large sustained rise in plasma noradrenaline concentration. Idazoxan 300 μg kg−1 and 1000 μg kg−1 i.v. did not prevent B‐HT 958‐induced falls in mean arterial pressure, heart rate and plasma noradrenaline concentration. Responses to B‐HT 958 were unaffected by idazoxan 20 μg i.c.v.
B‐HT 958‐induced falls in mean arterial pressure, heart rate and plasma noradrenaline concentration were significantly attenuated by i.v. administration of the dopamine receptor antagonist, sulpiride 300 μg kg−1. Sulpiride 10 μg and 50 μg i.c.v. caused inhibition of B‐HT 958 hypotension and bradycardia similar to that of intravenous sulpiride. After i.c.v. sulpiride, B‐HT 958 did not cause a significant fall in plasma noradrenaline concentration.
A combination of idazoxan 1000 μg kg−1 i.v. and sulpiride 300 μg kg−1 i.v. did not cause further significant inhibition of B‐HT 958 hypotension and bradycardia compared with sulpiride 300 μg kg−1 i.v. alone. This combination however had a significantly greater effect in inhibiting B‐HT 958 hypotension than had idazoxan 1000 μg kg−1 alone, and almost completely blocked the B‐HT 958‐induced fall in plasma noradrenaline concentration.
These results suggest that in the anaesthetized rat the cardiovascular effects of B‐HT 958 are due to stimulation of dopamine receptors, probably located within the central nervous system, and not to stimulation of peripheral prejunctional α2‐adrenoceptors.
The mode of vasorelaxant action of 2‐ aminoisoquinoline, 1.3 (2H.4H)‐dione, a novel ‘intracellular calcium inhibitor’
Authors: Hester R.K. , Satake N. , Shibata S. , Ueda S. , Yamahara J. 
Published: July 2012

In rabbit aorta, pretreatment with 2‐aminoisoquinoline, 1.3 (2H.4H)‐dione (AQ, 10−5 M and 10−4 M) shifted the concentration‐response relationship to noradrenaline (NA, 10−9 M to 10−4 M) in a parallel manner whereas the agent (10−4 M) failed to affect the response to potassium and only slightly depressed Ca2+‐induced contractions in a Ca2+‐free medium in the presence of K+ (40 mM).
Ca2+‐entry blockers such as nifedipine and diltiazem (10−6 M and 10−5 M) had very weak or no apparent effects on the response to NA but markedly attenuated or abolished the K+‐ and Ca2+‐induced contractions.
Following incubation of tissues for 15 min in a Ca2+‐free medium with low EGTA (0.01 mM) and methoxyverapamil (D600, 10−5 M), NA (3 × 10−7 M) caused a phasic (transient) contraction and the subsequent application of Ca2+ (2mM) resulted in a tonic contraction. This NA‐induced, Ca2+‐dependent, D600‐insensitive contraction was inhibited by AQ (10−5 M and 10−4 M) in a concentration‐dependent manner. This suggests that the inhibitory action of AQ may be related to Ca2+ entry through specific receptor activated pathways.
Following incubation of tissues for 30 min in a Ca2+‐free medium with high EGTA (2.0 mM), NA (10−5 M) caused a contraction of rabbit aorta which is dependent upon release of intracellular Ca2+, but the response was 50% to 60% less than that in a normal medium. This contraction was inhibited by AQ (10−5 M and 10−4 M) and nitroglycerin (10−5 M) but not by nifedipine or diltiazem. The inhibitory action of combined treatment with AQ and nitroglycerin (10−5 M) on the response to NA was not different from that of either agent alone.
These results suggest that AQ may have inhibitory actions on the release of intracellular Ca2+ and also on Ca2+‐entry through D600‐insensitive, receptor‐activated Ca2+ pathways in rabbit aorta.
α2‐Adrenergic hyperpolarization is not involved in slow synaptic inhibition in amphibian sympathetic ganglia
Authors: Rafuse Paul E. , Smith Peter A. 
Published: July 2012

The adrenaline‐induced hyperpolarization (AdH), slow inhibitory postsynaptic potential (slow i.p.s.p.) and hyperpolarizing phase of the response to methacholine (MChH) in Rana pipiens sympathetic ganglia were studied by means of the sucrose‐gap technique.
Desmethylimipramine (DMI, 0.5 μM) lowered the EC50 for adrenaline from 1.65 μM (1.23–2.21 μM, n = 10) to 0.30 μM (0.21–0.41 μM, n = 8). DMI did not potentiate the slow i.p.s.p. or the MChH.
Propranolol, sotalol or prazosin (1 μM) did not antagonize the AdH. The response was antagonised by phentolamine (IC50 = 0.53 μM), yohimbine (IC50 = 6.2 nM) and idazoxan (IC50 = 0.59 μM). Yohimbine (0.1 μM) did not reduce the amplitude of the slow i.p.s.p. or the MChH.
The slow i.p.s.p. was eliminated in Ringer solution containing Cd2+ (100 μM): This concentration of Cd2+ did not reduce the amplitude of the MChH.
α‐Methylnoradrenaline produced a concentration‐dependent hyperpolarization with an EC50 of 0.31 μM (0.13–0.73 μM, n = 5), in the presence of DMI (0.5 μM).
These results are consistent with the hypothesis that the AdH may be generated by activation of a receptor similar to the mammalian α2‐adrenoceptor. No evidence was found in support of the hypothesis that an adrenergic interneurone is involved in the synaptic pathway for the slow i.p.s.p.
Attenuation by isosorbide dinitrate of coronary occlusion‐induced acidosis in the dog myocardium
Authors: Abiko Yasushi , Fukushi Yukio , Haga Naomi , Matsumura Hisao 
Published: July 2012

In dogs anaesthetized with pentobarbitone, the thorax was opened and myocardial pH measured continuously by the use of a glass pH electrode inserted in the left ventricular wall.
The left anterior descending coronary artery (LAD) was partially occluded so that the LAD flow could be reduced to a half or one‐third of the original flow (partial occlusion). LAD partial occlusion was continued for 90 min, drug or saline being infused for the last 60 min of this period.
LAD occlusion decreased myocardial pH significantly by 0.41 to 0.67 pH units, and increased ST segment of the surface electrocardiogram from 11.7 to 12.1 mV.
In dogs with non‐ischaemic normal hearts, isosorbide dinitrate (ISDN; 1 mg kg−1) did not change markedly either the LAD flow, myocardial pH or heart rate, whereas it decreased myocardial contractile force (determined by a strain gauge arch) slightly and both the systolic and diastolic blood pressure markedly.
In dogs with partial LAD occlusion, ISDN (1 mg kg−1) increased myocardial pH significantly and decreased blood pressure, but did not change ST segment elevation in an epicardial lead.
These results indicate that ISDN attenuates ischaemia‐induced acidosis without attenuating ischaemia‐induced ST elevation in the dog myocardium.
Dopamine‐induced amylase secretion from rat parotid salivary gland in vitro: an effect mediated via noradrenergic and cholinergic nerves.
Authors: Hata Fumiaki , Ishida Hajime , Kondo Etsuo 
Published: July 2012

The effect of dopamine on amylase secretion by rat parotid tissue was examined in vitro.
Dopamine induced marked amylase secretion from the tissue in a dose‐dependent manner. Its EC50 value was about 4 μM and the maximal response was obtained at a concentration of 100 μM.
The dopamine‐induced secretion was inhibited by the dopamine‐antagonists haloperidol, (+)‐butaclamol and spiroperidol.
Atropine reduced the dopamine‐induced secretion significantly, and physostigmine enhanced the secretion.
Parasympathectomy of the gland resulted in a significant decrease in the dopamine‐induced secretion, but did not reduce the secretion induced by dopamine with atropine.
Dopamine‐induced ACh release from parasympathetic nerve terminals in the tissue was studied in tissue preparations that had been loaded with [3H]‐choline. Dopamine elicited Ca2+‐sensitive tritium release, and dopamine antagonists or parasympathectomy prevented this release.
Sympathectomy or reserpine treatment of rats resulted in significant decrease in the dopamine‐induced secretion, but increase in noradrenaline (NA)‐ or isoprenaline‐induced secretion.
Dopamine‐induced NA release was studied by preloading the parotid tissue with [3H]‐NA. Dopamine induced Ca2+‐sensitive tritium release, and dopamine antagonists or sympathectomy prevented the release.
Several lines of circumstantial evidence strongly suggested that dopamine has a specific site for action in the parotid tissue that is independent of NA receptors.
In sympathectomized or reserpine‐treated glands, atropine completely inhibited the dopamine‐induced amylase secretion, suggesting that dopamine did not have a direct effect on postsynapses.
These findings indicate that dopamine induces amylase secretion in two indirect ways mediated through ACh and NA released from parasympathetic and sympathetic nerve terminals, respectively.
P2‐purinoceptors regulate surfactant secretion from rat isolated alveolar Type II cells
Authors: Rice Ward R. , Singleton Fannie M. 
Published: July 2012

Rat isolated alveolar Type II cells were utilized to examine the effect of purine and pyrimidine analogues on secretion of pulmonary surfactant.
ATP potently stimulated [3H]‐phosphatidylcholine ([3H]‐PC) secretion in a time‐ and dose‐dependent manner. The effect of ATP was noted by one hour of exposure and persisted for three hours. The EC50 (concentration producing 1/2 the maximal response) for ATP‐induced [3H]‐PC secretion was 100 nM.
ADP was also a potent secretagogue for surfactant secretion, but AMP and adenosine had no significant effect on surfactant secretion at concentrations < 250 μM. The EC50 for ADP‐induced [3H]‐PC secretion was 250 nM.
Other purine and pyrimidine nucleotides (ITP, GTP, CTP, TTP) were examined for their effect on [3H]‐PC secretion. All purine and pyrimidine triphosphates examined significantly augmented [3H]‐PC secretion, but were much less potent than ATP. The EC50s were ITP = 10 μM; GTP = 100 μM; CTP = 250 μM; TTP = 100 μM.
Neither 8‐phenyltheophylline (10 μM, a P1‐purinoceptor antagonist), propranolol (100 μM, a β‐adrenoceptor antagonist), nor indomethacin (10 μM, a prostaglandin synthetase inhibitor) inhibited ATP‐induced [3H]‐PC secretion from isolated Type II cells.
These data provide evidence for regulation of surfactant secretion from alveolar Type II cells by a P2‐purinoceptor.
The classification of peripheral 5‐HT2‐like receptors using tryptamine agonist and antagonist analogues
Authors: Leff P. , Martin G.R. , Morse J.M. 
Published: July 2012

In a previous study, we attempted to verify the classification of 5‐hydroxytryptamine2 (5‐HT2) receptors in three vascular tissues, by use of the conventional antagonists, ketanserin, spiperone, methysergide and trazodone. However, it was not possible to conclude homogeneity of the receptor type in the three tissues due to the inconsistent behaviour of these antagonists, in particular, their apparently variable affinities between the tissues. These results led to the reliability of the conventional antagonists being questioned as receptor probes.
In the present study, a set of tryptamine analogues were investigated in two of the tissues, the rabbit aorta and the rat jugular vein. Unlike the conventional antagonists, these compounds bear a close chemical relation to the natural agonist, 5‐HT.
In both tissues, α,α‐dimethyltryptamine demonstrated apparently simple competitive antagonism of 5‐HT‐induced constrictions. Its affinity was estimated to be the same in each case.
The affinities and relative efficacies of 5‐HT, 5‐cyanotryptamine, N,N‐dimethyltryptamine and N‐benzyl‐5‐methoxytryptamine were also found to be indistinguishable between the two tissues.
Unlike the conventional 5‐HT2 receptor antagonists, these tryptamine analogues failed to distinguish between the 5‐HT receptors in the rabbit aorta and rat jugular vein implying that they truly belong to the same class. In view of this result, it is suggested that simple tryptamine analogues are more reliable probes for 5‐HT receptor classification than ligands which bear little or no chemical relation to the natural agonist.
Cytostatic action of two nitrosoureas derived from cysteamine
Authors: Bourut Charlotte , Chenu Evelyne , Godenèche Denise , Madelmont Jean‐Claude , Marla René , Mathé Georges , Meyniel Gaston 
Published: July 2012

2‐Chloroethyl nitrosocarbamoylcystamine or ICIG‐1325 (CNCC) is a lipid‐soluble isomeric mixture of nitrosoureas.
Its dose‐effect relationship on L1210 leukaemia is characterized by a large maximally efficient dose‐range (MEDR), greater than that of other nitrosoureas. CNCC also demonstrated significant therapeutic activity on intracerebrally (i.c.) transplanted L1210 leukaemia and on six transplanted solid tumours, TM2 mammary carcinoma, M555 ovarian carcinoma, B16 melanoma, glioma 26, 3LL, Lewis lung carcinoma and colon 26 carcinoma. It was inactive on fibrosarcoma ICIG‐Ci4. Its antitumour activity spectrum is wider than that of the related compounds 2‐[3‐(2‐chloroethyl) 3‐nitrosoureido]D‐glucopyranose (CZT), (chloro‐2‐ethyl)‐1 (ribofuranosyl‐isopropylidene‐2′‐3′paranitrobenzoate‐5′)‐3 nitrosourea (RFCNU), and (chloro‐2‐ethyl)‐1 (ribopyranosyl triacetate‐2′‐3′‐4′)‐3 nitrosourea (RPCNU).
A study of its metabolic disposition in animals has shown that CNCC undergoes extensive first‐pass metabolism leading to the formation of four main plasma metabolites.
These metabolites are water‐soluble nitrosoureas that arose from the bioreduction of the disulphide bridge followed by the methylation and the oxidation of the thiol groups.
Experimental screening was performed with these chemically synthesized metabolites. Both N'‐(2‐chloroethyl)‐N‐[2‐(methylsulphinyl)ethyl]‐N'‐nitrosourea (CMSOEN2) and N'‐(2‐chloroethyl)‐N‐[2‐(methylsulphonyl)ethyl]‐N'‐nitrosourea (CMSO2EN2) are very active on L1210 leukaemia grafted intraperitoneally (i.p.) and i.c., L40 leukaemia, B16 melanoma, glioma 26 and Lewis lung carcinoma. Their effectiveness is better than that of the parent compound CNCC. In addition, the percentage of mice cured after CMSOEN2 or CMSO2EN2 treatment is increased especially on B16 melanoma and glioma 26.
Haematological toxicity of both active metabolites is lower than that of CNCC, particularly on platelets which is the main toxicity location due to nitrosoureas.