bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bicarbonate‐dependence of responses to ethylenediamine in the guinea‐pig isolated ileum: involvement of ethylenediamine‐monocarbamate
Authors: Kerr David I.B. , Ong Jennifer 
Published: July 2012

γ‐Aminobutyric‐acid (GABA)‐mimetic responses were induced by ethylenediamine (EDA) in the isolated ileum of the guinea‐pig maintained in bicarbonate buffered Krebs‐Henseleit (KBC) solution, pH 7.4, 37°C, the responses consisting of a contraction followed by a relaxation. There were no such responses to EDA in bicarbonate‐free phosphate buffered (KPO) or HEPES buffered (KHO) Krebs solution, gassed with 100% O2, pH 7.4, 37°C, yet the ileum responded to GABA in bicarbonate‐free Krebs solution.
Similar GABA‐mimetic responses were induced by EDA in the isolated ileum maintained in bicarbonate‐free KPO or KHO modified Krebs solution, gassed with O2, if HCO3− (5 mm) was first added immediately before the test dose of EDA (0.1–1 mm), the threshold [HCO3−] being 2 mm for EDA‐induced responses in these preparations. However, ileal GABA‐mimetic responses were induced in bicarbonate‐free KPO or KHO solutions by EDA that had been pretreated with carbon dioxide, where the final [HCO3−] in the bath did not exceed 25 μm.
Ethylenediamine monocarbamate (synthetic EDAC) released [3H]‐GABA from preloaded segments of ileum maintained in bicarbonate‐free KPO or KHO solution containing amino‐oxyacetic acid and β‐alanine, the release being sensitive to 3‐mercaptopropionic acid which prevents GABA release. EDA itself did not evoke any such release in the absence of bicarbonate, but released [3H]‐GABA from segments maintained in KBC solution.
GABA‐mimetic responses were induced by EDAC in the isolated ileum maintained in bicarbonate‐free KPO solution, as was a δ‐aminovalerate‐sensitive depression of ileal twitch responses elicited by transmural stimulation, all of which were also sensitive to 3‐mercaptopropionic acid.
It is concluded that GABA‐mimetic responses to EDA in the isolated ileum of the guinea‐pig, maintained in normal Krebs bicarbonate medium, result from the release of endogenous GABA by ethylenediamine monocarbamate formed through the rapid reaction of EDA with the carbon dioxide of bicarbonate buffered Krebs solution. Furthermore, in the ileum, HCO3− ions per se are not necessary for this GABA‐releasing property of EDA if the latter is first converted to the monocarbamate, since synthetic ethylenediamine monocarbamate elicits ileal GABA‐mimetic responses in the total absence of bicarbonate.
Antagonism of vasoconstriction induced by platelet‐activating factor in guinea‐pig perfused hearts by selective platelet‐activating factor receptor antagonists
Authors: Piper Priscilla J. , Stewart A.G. 
Published: July 2012

Platelet‐activating factor (Paf) is a potent coronary vasoconstrictor in rat, guinea‐pig, dog and pig. The present study investigated the mechanism and duration of action of Paf in guinea‐pig isolated, Krebs‐perfused hearts.
Dose‐related and sustained decreases in cardiac contractility and increases in coronary perfusion pressure were elicited by bolus doses of Paf (0.3–100 pmol).
Platelet‐activating factor (30 pmol) induced increases in the production of immunoreactive thromboxane B2 (TXB2), leukotriene B4 (LTB4) and LTC4, but not 6‐keto‐prostaglandin F1α (6‐keto‐PGF1α). In addition, the release of leukotriene‐like material following Paf was observed using on‐line superfusion bioassay.
The coronary vasoconstrictor actions of Paf were partially antagonized by the leukotriene receptor antagonist, FPL 55712 (1.9 μm), or by indomethacin (2.8 μm). The combined use of these compounds did not result in further significant inhibition.
The Paf receptor antagonists, BN 52021 (30 μm) and L 652, 731 (10 μm), antagonized both the increase in coronary perfusion pressure and the decrease in cardiac contractility induced by Paf (10–100 pmol) in a surmountable and relatively selective manner.
The effects of a bolus dose of 100 pmol Paf were sustained in excess of 18 min. Exogenous Paf underwent little metabolism on passing through the coronary circulation with only 2% being converted to lyso‐Paf and approximately 4% being retained by the heart after 18 min of perfusion.
These results suggest that the coronary vasoconstrictor actions of Paf are partially dependent on the release of vasoactive arachidonic acid metabolites. The extraordinary potency and the long‐lasting action of Paf indicate a potential role for this pro‐inflammatory mediator in disorders of the coronary circulation.
Inhibition of Uptake1 by dopexamine hydrochloride in vitro)
Authors: Mitchell Paul D. , Smith George W. , Wells Edward , West Philip A. 
Published: July 2012

Dopexamine hydrochloride, a compound under evaluation for the acute treatment of heart failure, was examined in vitro for its ability to prevent neuronal uptake of noradrenaline.
Despite possessing only weak β1‐adrenoceptor agonist activity in paced guinea‐pig left atria, dopexamine hydrochloride was only 23 times less potent than isoprenaline in augmenting responses of field‐stimulated atrial preparations.
This potent effect was not observed in field‐stimulated atria depleted of noradrenaline by reserpine and in the presence of cocaine was greatly reduced (1 μm) or abolished (50 μm).
Dopexamine hydrochloride (3 μm) potentiated the inotropic effect of exogenous noradrenaline in paced atria, thereby resembling cocaine (10 μm) and dopamine (30 μm), both of which are known inhibitors of Uptake1.
The sodium‐dependent uptake of [3H]‐noradrenaline into rabbit brain synaptosomes was prevented by dopexamine hydrochloride (IC50 26 nm) and cocaine (IC50 108 nm), as well as by two other catecholamines used in the treatment of heart failure, dopamine (IC50 270 nm) and dobutamine (IC50 380 nm).
The cardiac stimulant effect of dopexamine hydrochloride reported in dogs and in patients with heart failure, may therefore be due in part to potentiation of endogenous catecholamines.
External ATP mimics carbachol in initiating calcium mobilization from pancreatic β‐cells conditioned by previous exposure to glucose
Authors: Gylfe Erik , Hellman Bo 
Published: July 2012

Exposure to ATP (2–200 μm) resulted in a prominent peak of 45Ca efflux, when β‐cell‐rich pancreatic islets from ob/ob‐mice were perifused with a Ca2+‐deficient medium. ADP and the stable α/β‐methylene analogues of ATP and ADP also had stimulatory effects.
The nucleotide initiation of 45Ca efflux mimicked that obtained with carbachol both in requiring previous exposure to glucose and in being more pronounced after replacing extracellular Na+ by K+.
It was possible to induce repeated peaks of stimulated 45Ca efflux, when the exposure to ATP was interrupted with intervals of perifusion with glucose‐containing media.
The observations are consistent with the existence of P2‐purinoceptors in islets, suggesting that these receptors mediate a similar mobilization of calcium as noted when activating polyphosphoinositide breakdown with carbachol. In view of the high contents of ATP and ADP in the β‐cell secretory granules, activation of P2‐purinoceptors should be considered as a possible mechanism for amplification of the initial insulin secretory response.
Effect of bradykinin antagonists on bradykinin‐induced plasma extravasation, venoconstriction, prostaglandin E2 release, nociceptor stimulation and contraction of the iris sphincter muscle in the rabbit
Authors: Griesbacher Thomas , Lembeck Fred 
Published: July 2012

The inhibition of the bradykinin‐induced plasma extravasation by six bradykinin (Bk) antagonists was tested on rabbit skin. All of them showed inhibitory effects without an agonistic action in the doses used. B4310 (Lys‐Lys‐3‐Hyp‐5,8‐Thi‐7‐DPhe‐Bk) was the most active antagonist and was therefore used in the subsequent experiments.
B4310 (5–500 nm) antagonized the bradykinin‐induced reduction of the venous outflow from the rabbit isolated ear in a dose‐dependent manner without affecting the arterial vasoconstriction induced by angiotensin II.
The bradykinin‐induced release of prostaglandin E2 (PGE2) from the perfused rabbit ear was reduced by 63% when B4310 (800 nm) was infused before, during and after the bradykinin injection.
Bradykinin was injected into the ear artery of anaesthetized rabbits and the reflex hypotensive response was used as indicator of the nociception. The response was antagonized by a local infusion of B4310 (50 and 500 nm). The antagonism was dose‐dependent and reversible. The parallel shift of the dose‐response curve to bradykinin suggests a competitive inhibition. However, B4310 did not antagonize acetylcholine‐induced nociceptor stimulation.
B4310 inhibited bradykinin‐induced stimulation of the trigeminal nerve which results in a substance P‐mediated contraction of the iris sphincter muscle. A pA2 of 7.59 was calculated. B4310 did not inhibit capsaicin‐induced contractions.
It is concluded that B4310 inhibits specifically five different actions of bradykinin which are related to its possible pathophysiological role.
Membrane mechanism associated with muscarinic receptor activation in single cells freshly dispersed from the rat anococcygeus muscle
Authors: Byrne N.G. , Large W.A. 
Published: July 2012

The mechanism of action of carbachol was studied on freshly dispersed cells of the rat anococcygeus using microelectrodes and patch pipettes.
Micro‐ionophoretic application of carbachol evoked reproducible depolarizations which were reduced or blocked by atropine (10−7‐10−6 m). The time courses of the responses to noradrenaline and carbachol were similar.
The reversal potential of the carbachol‐induced response was −3.8 mV and similar to the value (‐6.2 mV) found for noradrenaline.
During the response to carbachol the membrane conductance was increased. At depolarized membrane potentials carbachol evoked biphasic membrane responses suggesting an increase in two separate ionic conductances.
With patch pipettes in the whole‐cell configuration under voltage‐clamp, carbachol produced an inward current at a holding potential of −50 mV. The inward current was associated with an increase in membrane conductance with an equilibrium potential of about 0 mV.
It is suggested that muscarinic receptors and adrenoceptors in the rat anococcygeus may activate similar membrane conductances. The most prominent mechanism is an increase in chloride ion conductance.
Platelet‐leukocyte interaction: activation of rabbit platelets by FMLP‐stimulated neutrophils
Authors: Coëffier Eliane , Joseph Danielle , Prévost Marie‐Christine , Vargaftig B. Boris 
Published: July 2012

The effect of the chemotactic peptide, N‐fonnyl‐l‐methionyl‐l‐leucyl‐l‐phenylalanine (FMLP) was studied on cells in whole rabbit blood or on a mixture of purified rabbit platelets and neutrophils.
In blood, FMLP triggered cell aggregation (measured by electrical impedance) which was dependent upon the concentration of FMLP (9.9 ± 0.7 and 5.2 ± 1.2 ohms at 1 and 0.01 μm FMLP respectively). This aggregation was accompanied by a strong decrease in platelet counts (54.6 ± 6.0 and 45.6 ± 3.8% for 1 and 0.01 μm FMLP respectively) and by a smaller decrease in neutrophil counts (25.0 ± 1.9 and 12.9 ± 1.7% at 1 and 0.01 μm FMLP respectively).
When purified platelets and neutrophils were co‐incubated, the addition of 0.1 μm induced a marked aggregation (50.0 ±1.6 vs. 19.5 ±1.6% of light transmission, n = 8, P < 0.001), ATP secretion (8.4 ± 1.0 vs. 0.1 ± 0.1 nmol ml−1, n = 6, P < 0.001) and a decrease in platelet counts. FMLP induced aggregation of purified neutrophils and release of lysozyme but lacked direct platelet‐stimulating effects. The release of lactate dehydrogenase, a cytoplasmic marker and lysozyme were unchanged under the interaction conditions.
Platelet activation was reduced by about 30% with 100 μm aspirin or indomethacin and by about 70% with 100 μm BW 755C. Two Paf‐acether antagonists, BN 52021 (100 μm) and WEB 2086 (1 μm) suppressed platelet activation by 70–80%.
The supernatant of FMLP‐stimulated neutrophils induced platelet activation only when bovine serum albumin was present. Rabbit neutrophils stimulated in the presence of serum albumin by 1 μm FMLP formed 2 nm Paf‐acether of which half was released to the extracellular medium.
Our results indicate that the stimulation of neutrophils by FMLP induces platelet activation in whole blood and on isolated cells and that both arachidonic acid‐metabolites and Paf‐acether participate in platelet activation.
Effects of ouabain on isolated cerebral and femoral arteries of the cat: a functional and biochemical study
Authors: Marín Jesús , Sánchez‐Ferrer Carlos F. , Salaices Mercedes 
Published: July 2012

This study analyzes the mechanisms involved in the responses to ouabain in cat cerebral and femoral arteries and characterizes the electrogenic Na+ pump present in these vessels. The latter was accomplished by measurement of [3H]‐ouabain binding to arterial membrane fractions, K+‐elicited relaxation and ouabain‐sensitive 86Rb+ uptake.
Ouabain induced transient contraction in cylindrical segments of cerebral arteries. This contraction was reduced by verapamil (3 × 10−6 m) and Ca2+‐removal from the medium but was not modified by phentolamine (3 × 10−6 m) or pretreatment with reserpine. However, the contraction elicited by ouabain in femoral artery segments lasted longer, and was reduced by Ca2+‐omission, phentolamine or reserpine, but remained unaffected by verapamil.
The immersion of the arteries in low‐Na+ (25 mm) medium abolished the contraction caused by ouabain.
The exposure of the arteries to a K+‐free medium induced a small transient increase in tension, and the subsequent application of K+ (7.5 mm) elicited a marked relaxation. This effect was greater in cerebral than in peripheral arteries, and was suppressed by ouabain (10−4 m).
Scatchard analysis of the [3H]‐ouabain binding to arterial membrane fractions suggested a single class of binding sites. The KD values for both kinds of arteries were of similar order, while the Bmax value was greater in cerebral than in femoral arteries.
Total and ouabain‐sensitive 86Rb+ uptakes were greater in cerebral than in femoral vessels.
These results indicate that: (1) ouabain‐induced contraction of cerebral arteries is due to a direct effect on vascular smooth muscle cells, while in femoral arteries it is due to noradrenaline release from adrenergic nerve terminals; and (2) the electrogenic Na+ pump activity is greater in cerebral than in peripheral arteries.
Actions of vanadate on vascular tension and sodium pump activity in cat isolated cerebral and femoral arteries
Authors: Sánchez‐Ferrer Carlos F. , Marín Jesús , Lluch Magdalena , Valverde Angel , Salaices Mercedes 
Published: July 2012

The mechanisms involved in the responses induced by sodium vanadate (Va3 VO4) on cat cerebral and femoral arteries were studied. The possibility that these responses were due to Na+, K+‐ATPase inhibition was investigated by measuring the effect of vanadate on [3H]‐ouabain binding to arterial membrane fractions, K+‐induced vasodilatation and ouabain‐sensitive 86Rb+ uptake.
The vanadium compounds (Na3VO4, VOSO4, VCl3 and O5V3) induced similar, concentration‐dependent contractions in each kind of artery, the cerebral vessels being the most sensitive to these compounds.
Exposure of the arteries to a low‐Na+ (25 mm) solution suppressed the contraction caused by vanadate in femoral but not in cerebral arteries.
Vanadate‐induced contractions were reduced in Ca2+‐free medium but remained unaffected by 3 × 10−6 m phentolamine, reserpine pretreatment or 3 × 10−6 m verapamil in both kinds of artery.
The addition of 7.5 mm K+ to the arteries immersed in a K+‐free solution induced vasodilatation, which was not modified by 10−3 m vanadate.
The consecutive administration of ouabain (10−4 m) and vanadate (10−3 m) (or vice versa), or the simultaneous administration of both agents (10−8 to 10−3 m) appeared to produce an additive contraction in both types of artery.
Vanadate (10−7 to 10−3 m) did not displace the [3H]‐ouabain binding to arterial membrane fractions of these arteries, whereas 10−4 m ouabain did.
In both kinds of artery, total 86Rb+ uptake was reduced by ouabain (10−8 to 10−3 m), in a concentration‐dependent manner, whereas it was not modified by vanadate (10−8‐10−3 m).
These results suggest that vanadate induces contraction in both types of artery by a mechanism unrelated to Na+, K+‐ATPase inhibition. Such a mechanism is likely to be related to inhibition of the Ca2+‐ATPase of the cell membrane and/or the sarcoplasmic reticulum.
Comparison of mucus flow rate, radiolabelled glycoprotein output and smooth muscle contraction in the ferret trachea in vitro
Authors: Kyle Helen , Widdicombe J.G. , Wilffert B. 
Published: July 2012

The concentration‐response curves for rate of mucus output, labelled‐glycoprotein output and smooth muscle contraction in response to methacholine, phenylephrine and salbutamol were determined in the ferret trachea in vitro.
The potencies of methacholine and phenylephrine are both in order: smooth muscle contraction, glycoprotein output, rate of mucus output.
At lower concentrations methacholine is more potent than is phenylephrine on smooth muscle contraction, glycoprotein output and rate of mucus output.
Concentration‐response curves for salbutamol show very little change in rate of mucus output but a large increase in glycoprotein output.
It is concluded that the glycoprotein output induced by salbutamol may come from a source different from those induced by methacholine and phenylephrine.
Role of α1‐ and α2‐adrenoceptors in catecholamine‐induced hyperglycaemia, lipolysis and insulin secretion in conscious fasted rabbits
Authors: Moratinos J. , Carpene C. , de Pablos I. , Reverte M. 
Published: July 2012

In conscious fasted rabbits an intravenous infusion of clonidine (2 μg kg−1 min−1) induced hyperglycaemia. The increase in blood glucose was accompanied by an inhibition of insulin secretion and basal lipolysis.
Yohimbine infused at a rate of 20 μg kg−1 min−1 suppressed clonidine‐induced hyperglycaemia and blocked the inhibitory effect on insulin secretion mediated by the α2‐adrenoceptor agonist.
The intravenous infusion of amidephrine (10 μg kg−1 min−1) induced an increase in insulin secretion in the absence of patent hyperglycaemia. Prazosin, 0.3 mg kg−1 s.c. selectively antagonized the effect of amidephrine on insulin secretion.
Isoprenaline infusion (4.4 μg kg−1 min−1) evoked a significant increase in blood glycerol and immunoreactive insulin plasma levels. Both responses were clearly attenuated when α2‐adrenoceptors were simultaneously stimulated by selective (clonidine) and less selective (phenylephrine, 20 μg kg−1 min−1) agonists.
Amidephrine infusion did not induce appreciable changes in blood glycerol nor did it modify, isoprenaline‐induced lipolytic response.
Simultaneous infusion of isoprenaline and amidephrine induced a remarkable increase in insulin secretion.
It is concluded that in normal fasted rabbits stimulation of α2‐adrenoceptors depresses basal and β‐adrenoceptor mediated lipolysis and insulin secretion. On the other hand, selective stimulation of α1‐adrenoceptors does not affect lipolysis but induces insulin release. Simultaneous stimulation of α1‐ and β‐adrenoceptors potentiates the insulin secretory response.
Impairment of endothelium‐dependent relaxation: an early marker for atherosclerosis in the rabbit
Authors: Jayakody Laal , Kappagoda Tissa , Senaratne Manohara P.J. , Thomson Alan B.R. 
Published: July 2012

Cholesterol feeding of rabbits impairs the endothelium‐dependent relaxation (EDR) evoked by acetylcholine (ACh) in the aorta. The experiments described in this paper were undertaken to examine the influence of age upon this phenomenon.
Rabbits aged 8 weeks and 46 weeks were fed a diet containing 2% cholesterol and other lipids for 4 weeks. Age‐matched control animals were fed a standard rabbit diet. The concentrations of cholesterol and triglycerides in plasma were measured and the extent of atherosclerosis was estimated by staining the aortae with Sudan Red. Light and electron microscopy were undertaken also.
Rings of aorta were prepared for recording isometric tension. They were contracted with noradrenaline (NA) and EDR elicited by adding ACh.
The young rabbits showed weight gain, hypercholesterolaemia, prominent Sudan Red staining, together with scanning and transmission electron microscopic (SEM and TEM) features of cholesterol‐induced atherosclerosis. The older animals showed significant weight loss and hypercholesterolaemia. The aortae of these animals showed no significant sudanophilia or light microscopic features of atherosclerosis. The SEM appearances were similar to the young animals fed cholesterol.
EDR to ACh was significantly impaired in both groups of cholesterol‐fed rabbits. The maximal relaxations to ACh in young control and cholesterol‐fed rabbits were 46.4 ± 2.9% and 24.0 ± 4.3% (mean ± s.e. mean, n = 8, P < 0.05) of the contractile response to NA (1 μmol 1‐1). The corresponding results in the age control and cholesterol‐fed rabbits were 31.8 ± 3.9% and 9.1 ± 1.5% (n = 9, P < 0.05).
The young rabbits were far more susceptible to cholesterol‐induced atherosclerosis than older animals and these changes were accompanied by loss of EDR. In the older animals the loss of the latter property was not accompanied by a significant degree of atherosclerosis although hypercholesterolaemia was present.
PA2 values for antagonists of platelet activating factor on aggregation of rabbit platelets
Authors: O'Donnell Stella R. , Barnett Christopher J.K. 
Published: July 2012

The relative potencies, and equilibrium dissociation constants, for nine antagonists of platelet activating factor (Paf) have been determined on rabbit platelets (in diluted platelet‐rich plasma (PRP)) in experiments in which the aggregatory response to Paf was measured.
Log concentration‐response (% maximum) curves to Paf were obtained in the absence (controls) and presence of different concentrations of each Paf antagonist drug. The antagonists shifted the Paf curves to a higher concentration range and the slopes of the Schild plots, constructed from these data, suggested that the drugs were competitive antagonists of Paf. The slopes of the Schild plots for CV‐3988 and SRI 63–119 were > 1.
The pA2 values (pKB values in parentheses) were: WEB 2086 7.31 (7.63); SRI 63–119 6.95; L‐652,731 6.71 (6.73); BN 52021 6.38 (6.47); SRI 63–072 6.36 (6.43); CV‐3988 5.87; 48740 RP 4.97 (5.07); ketotifen 4.94 (4.95); thiazinamium 4.73 (4.76).
This study provides, for the first time, some functional response data for Paf antagonists (pKB values) which are in an appropriate form for use in classifying putative Paf receptors. The study also provides the comparative potencies of these Paf antagonists in inhibiting Paf‐induced platelet aggregation. WEB 2086 was the most potent of the drugs examined.