bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of calcium channel blockers on gastric emptying and acid secretion of the rat in vivo
Authors: Brage R. , Cortijo J. , Esplugues J. , Esplugues J. V. , Martí‐Bonmatí E. , Rodriguez C. 
Published: July 2012

Experiments were designed to evaluate the effects of three calcium channel blockers (verapamil, diltiazem and cinnarizine) on gastric emptying and secretion in the rat
Pretreatment with the calcium blockers delayed gastric emptying of phenol red in a dose‐dependent manner. Verapamil was the most effective of the agents tested.
Verapamil and diltiazem inhibited gastric acid secretion in the pylorus‐ligated rat without affecting pepsin output. Cinnarizine was ineffective in this model.
When the perfused lumen of the anaesthetized rat was used, verapamil was found to inhibit responses to carbachol or histamine more than those to pentagastrin. Further, we found a greater sensitivity to verapamil for basal compared with vagal‐stimulated (2‐deoxy‐D‐glucose) acid secretion. Neither diltiazem nor cinnarizine modified gastric acid secretion in this experimental model.
These findings are discussed in relation to the role of extracellular calcium in gastric motility and secretion, and the existence of a regional and functional selectivity for calcium blockers is proposed.
Muscarinic receptor modulation of release of [Met5]enkephalin immunoreactive material and catecholamines from the bovine adrenal gland
Authors: Barron B.A. , Hexum T.D. 
Published: July 2012

Muscarinic receptor modulation of secretion from the adrenal medulla was studied using retrogradely perfused bovine tissue.
Atropine, at a dose not affecting 1,1 dimethyl‐4‐phenylpiperizinium (DMPP)‐stimulated release, inhibitied the acetylcholine (ACh)‐stimulated release of noradrenaline and [Met5]enkephalin‐immunoreactive material (ME‐IRM).
DMPP‐stimulated release of catecholamines and ME‐IRM was potentiated by the addition of methacholine.
Pilocarpine significantly potentiated the release of noradrenaline only.
Methacholine, pilocarpine or muscarine, when infused alone, had no stimulatory affect on the basal release of ME‐IRM.
These findings suggest that the muscarinic receptors in the bovine adrenal medulla function by potentiating the release of ME‐IRM and catecholamines induced by nicotinic receptor stimulation.
Regional variation in the characteristics of histamine H1‐agonist mediated breakdown of inositol phospholipids in guinea‐pig brain
Authors: Carswell H. , Young J.M. 
Published: July 2012

The position of dose‐response curves for histamine‐induced accumulation of [3H]‐inositol 1‐phosphate ([3H]‐IP1) in lithium‐treated slices of guinea‐pig brain prelabelled with [3H]‐inositol differed significantly between cerebellum (EC50 5.1 ± 1.0 μM) and cerebral cortex (EC50 16.3 ± 0.7 μM). The Hill coefficients of the curves, 1.33 ± 0.28 and 1.24 ± 0.03, respectively, did not differ significantly.
2‐Methylhistamine, Nα,Nα‐dimethylhistamine and betahistine were partial agonists in both cerebellum and cerebral cortex, but all produced a greater percentage of the maximum response to histamine in cerebellar slices.
In hippocampal slices the response of the partial agonists was intermediate between that in cerebellum and that in cerebral cortex.
The four agonists produced an appreciable accumulation of [3H]‐inositol 1 ‐phosphate in cerebellar slices even in the absence of Li+ ion. The EC50 and Hill coefficients characterizing the dose‐response curves for the four agonists were the same whether 10 mM LiCl was present or not.
The affinity constant for mepyramine inhibition of the histamine‐induced response was similar in cerebellum, 4.2 ± 0.6 × 108 M−1, and cerebral cortex, 4.6 ± 1.0 × 108 M−1. Curves of mepyramine inhibition of the responses to a fixed concentration of histamine gave no indication of any second component in the response to histamine in either cerebellum or cerebral cortex.
The parameters of histamine inhibition of [3H]‐mepyramine binding were similar in homogenates of guinea‐pig cerebellum and cerebral cortex.
These results indicate that H1 ‐agonist‐induced accumulation of IP1 may not be as directly related to agonist‐receptor interaction as simple reaction schemes suggest.
Electrophysiological study of SR 42641, a novel aminopyridazine derivative of GABA: antagonist properties and receptor selectivity of GABAA versus GABAB responses
Authors: Desarmenien M. , Desaulles E. , Feltz P. , Hamann M. 
Published: July 2012

A new arylamino‐pyridazine γ‐aminobutyric acid (GABA) derivative, SR 42641, has been tested for its ability to antagonize the actions of GABA on mammalian sensory neurones.
SR 42641 and bicuculline reversibly decreased GABAA‐induced depolarizations and currents recorded intracellularly from dorsal root ganglion neurones (DRG). Dose‐response curves were shifted to the right in a parallel fashion. KB values (determined under voltage clamp conditions) were respectively 0.12 ±0.05 and 0.38 ± 0.08 μm. Similar values were obtained with current clamp recording conditions.
The study of the GABA‐induced Cl− current under voltage‐clamp conditions did not show any voltage‐dependency of the antagonist effect of SR 42641.
In nodose ganglion neurones, SR 42641 (0.4‐4.5 μm) did not alter the (‐)‐baclofen‐induced shortening of the calcium component of action potentials. At concentrations higher than 10 μm, SR 42641 itself prolonged calcium‐dependent action potentials.
Patch‐clamp recordings from DRG cultured neurones indicated that SR 42641 did not affect the calcium current responsible for sustained calcium entry into cells.
We conclude that SR 42641 is a potent competitive GABA antagonist, specific for the GABAA receptor. It does not act at the level of the chloride ionophore.
Acetylcholinesterase activity rises in rat cerebrospinal fluid post‐ictally; effect of a substantia nigra lesion on this rise and on seizure threshold
Authors: Appleyard Margaret E. , Green A. Richard , Greenfield Susan A. 
Published: July 2012

The activity of acetylcholinesterase (AChE) in the cerebrospinal fluid (CSF) of rats increased by 53% following an electroconvulsive shock (ECS) while non‐specific cholinesterase (nsChE) activity was unchanged.
A flurothyl‐induced seizure failed to elicit a change in the AChE activity of CSF.
A bilateral lesion of the substantia nigra pars reticulata abolished the rise in AChE activity in the CSF but did not diminish the increase of seizure threshold which follows a convulsion.
These data suggest that AChE is released from the substantia nigra following a seizure but indicate that the change is not associated with the rise in seizure threshold which occurs.
Recovery of prostacyclin synthesis by rabbit aortic endothelium and other tissues after inhibition by aspirin
Authors: Frazer C.E. , Ritter J.M. 
Published: July 2012

The effect of aspirin on prostacyclin (PGI2) and thromboxane B2 (TXB2) synthesis was studied in rabbits. Tissues were removed from animals killed at intervals after injection of aspirin, and incubated with Hanks' solution. PGI2 synthesis was monitored by radioimmunoassay of its hydrolysis product, 6‐ oxo‐prostaglandin F1α (6‐oxo‐PGF1α). TXB2 production in clotted blood, also measured by radioimmunoassay, was determined as an index of platelet cyclo‐oxygenase activity.
6‐oxo‐PGF1α and TXB2 production 0.5 h after aspirin were similarly inhibited to less than 5% of control in all incubations. Subsequent recovery of PGI2 synthesis occurred more rapidly in aortic endothelium than in other tissues, including aorta denuded of endothelium. Recovery of TXB2 production was slower than that of PGI2.
Intravenous cycloheximide prevented the partial recovery of PGI2 synthesis that otherwise occurred 6 h after aspirin, while intravenous epidermal growth factor increased recovery.
It is concluded that in the rabbit, cyclo‐oxygenase is synthesized more rapidly in aortic endothelium than in deeper layers of aorta, or in the other tissues studied.
Blockade by nifedipine of responses to intravenous bolus injection or infusion of α1‐and α2‐adrenoceptor agonists in the pithed rat
Authors: McGrath J.C. , O'Brien J.W. 
Published: July 2012

Nifedipine was tested against pressor responses in the pithed rat to ten agonists with varying selectivity for α1‐and α2‐adrenoceptors, injected as a bolus or infused intravenously: i.e. amidephrine, azepexole, cirazoline, indanidine, M7, methoxamine, noradrenaline (NA), oxymetazoline, phenylephrine and xylazine. Nifedipine, administered before the agonists, inhibited responses initiated by all agonists, usually for both the bolus and infusion responses.
With a bolus, blockade was significantly greater against the more prolonged, secondary components of the pressor responses. This demonstrates that calcium‐entry occurs during the secondary component of the a‐adrenoceptor‐mediated response and can be initiated by either α1‐or α2‐adrenoceptor subtypes.
The time courses of responses to infusion varied. Selective α1‐adrenoceptor agonists, with the exception of indanidine, did not produce a stable pressor response during the 20 min infusion time but α2‐adrenoceptor agonists did. Nifedipine reduced responses to infusion with no preference for α1‐or α2‐agonists. Phenylephrine and NA produced pressor responses which reached a peak and then declined during the remainder of the infusion.
The levels of NA in arterial and venous plasma were measured by h.p.l.c. during the infusion of NA. Arterial NA levels rose throughout the infusion whereas venous levels remained relatively unaffected. The absolute levels of plasma NA suggest that a large proportion of intravenously administered NA is removed in the pulmonary circulation and the remainder is removed in the systemic circulation with negligible recirculation.
The consequences of these results, for assessment of the mechanisms of action of adrenoceptor agonists and calcium entry blockers, are discussed.
Evidence that the mechanism of the inhibitory action of pinacidil in rat and guinea‐pig smooth muscle differs from that of glyceryl trinitrate
Authors: Bray Katharine M. , Newgreen D.T. , Small R.C. , Southerton J.S. , Taylor S.G. , Weir Sheila W. , Weston A.H. 
Published: July 2012

The effects of pinacidil have been compared with those of glyceryl trinitrate (GTN) using the aorta and portal vein of the rat and the trachealis and taenia caeci of the guinea‐pig.
In aorta, both pinacidil and GTN inhibited responses to noradrenaline and showed some selective inhibition of contractions to 20 mm K+. Responses to 80 mm K+ were little affected.
In trachealis, both pinacidil and GTN inhibited spontaneous tone and selectively relaxed spasms to 20 mm K+. Responses to 80 mm K+ were unaffected.
In portal vein, pinacidil completely inhibited spontaneous electrical and mechanical activity. GTN reduced the amplitude of tension waves and extracellularly‐recorded discharges, but increased the frequency of spontaneous electrical and mechanical activity.
In portal vein, pinacidil inhibited contractions to noradrenaline and selectively inhibited responses to 20 mm K+. GTN had little inhibitory effect on responses to either noradrenaline or K+.
In portal veins loaded with 86Rb as a K+‐marker, pinacidil significantly increased the 86Rb efflux rate coefficient whilst GTN had no effect on 86Rb exchange.
In taenia caeci, both pinacidil and GTN inhibited the spontaneous tone of the preparation. These inhibitory effects were not antagonized by apamin.
It is concluded that pinacidil and GTN do not share a common relaxant mechanism. Evidence has been obtained that pinacidil exerts its inhibitory effects by the opening of apamin‐insensitive, 86Rb‐permeable K+ channels.
Relaxant effect of the H2‐receptor antagonist oxmetidine on guinea‐pig and human airways
Authors: Advenier Charles , Gnassounou Jean Pierre , Scarpignato Carmelo 
Published: July 2012

The effects of three different H2‐receptor antagonists (cimetidine, ranitidine and oxmetidine) were tested on isolated preparations of guinea‐pig trachea and human bronchus against contractions induced by acetylcholine, histamine and potassium chloride (KCl). In addition, their influence on calcium concentration‐response curves in guinea‐pig tracheal spirals was examined in a potassium‐rich solution (30 mM). Finally, their effects were studied in vivo against acetylcholine and histamine‐induced bronchoconstriction in anaesthetized guinea‐pigs.
In guinea‐pig isolated trachea, oxmetidine—in contrast to cimetidine and ranitidine, which were completely inactive—induced a concentration‐dependent relaxation regardless of the excitatory stimulus: its—log EC50 values (i.e. the negative log concentration that caused a 50% relaxation) were 3.46 ± 0.11, 4.61 ± 0.09 and 4.20 ± 0.12 against acetylcholine, histamine and KCl, respectively. In Ca2+‐free, K+‐enriched solution, the compound was able to inhibit Ca2+‐induced contractions at concentrations close to those needed to counteract the spasmogenic effect of histamine in normal Krebs solution. Results obtained in the human bronchus preparation were similar to those observed in guinea‐pig tracheal spirals.
When tested against acetylcholine or histamine‐induced bronchoconstriction in vivo, oxmetidine (10 and 30 mg Kg−1 intravenously) significantly reduced the increase in pulmonary airway resistance (Raw) induced by both agents. Once again, cimetidine and ranitidine were completely ineffective.
In summary, oxmetidine displayed non‐specific antispasmogenic activity on guinea‐pig and human airways. This effect, which is independent of H2‐receptor blockade, represents a side‐effect of the drug which may be connected to its interference with Ca2+ influx and the action or release of intracellular Ca2+.
Effects of morphine on cardiovascular responses to acute myocardial ischaemia in rats
Authors: Chan Mo‐Yin , Dai Soter , Ko Wendy W.W. 
Published: July 2012

The effects of acute coronary artery ligation on cardiac rhythm and haemodynamics were studied in rats receiving either acute or chronic morphine‐treatment.
In chronic opiate‐treated animals, increasing concentrations of morphine sulphate were administered in drinking water over a 3 week period, and the development of morphine tolerance and dependence was verified by decreased analgesic responses to morphine in the tail‐immersion test and the occurrence of naloxone‐precipitated withdrawal syndromes, respectively.
Acute coronary artery ligation induced a decrease in blood pressure, a slight increase in heart rate, and ventricular tachycardia or fibrillation in anaesthetized rats.
The changes in blood pressure and heart rate following acute coronary artery ligation were not significantly altered by acute or chronic morphine administration.
The incidence and the time of onset of ventricular tachycardia or fibrillation were found to be significantly reduced and prolonged, respectively, in chronically morphine‐treated rats, but were not significantly affected by acute morphine administration in naïve animals.
These findings suggest that chronic morphine treatment lessens the occurrence of early ventricular arrhythmias caused by acute myocardial ischaemia in rats. The mechanism of this effect is unclear.
High and concentration‐proportional accumulation of [3H]‐nitrendipine by intact cardiac tissue
Authors: Lüllmann Heinz , Mohr Klaus 
Published: July 2012

The binding of [3H]‐nitrendipine to intact, electrically driven isolated left atria of guinea‐pigs was investigated over the concentration range 10−10 m to 3 × 10−5 m.
A high affinity binding site saturable in the nm range as found in ventricular homogenates could not be detected. Instead the accumulation of nitrendipine in intact atria was found to be proportional to the concentration from 10−10 m to 10−6 m; beyond 10−6 m the binding started to become saturated.
Nitrendipine was highly accumulated in atrial tissue. The cell: medium ratios amounted to about 120 in the range from 10−10 m to 10−6 m.
The concentration‐response curve for the negative inotropic action of nitrendipine yielded an ED50 of 3 × 10−7 m, thus lying within the range of concentration‐proportional accumulation.
The reduction of the contractile force proceeded faster (t1/2 10 min) than the uptake process (t1/2 ∼ 40 min) suggesting that it is the binding of nitrendipine into a superficial compartment, which interferes with the excitation‐contraction coupling.
The results suggest that the high concentration of nitrendipine present in hydrophobic cellular compartments such as the plasmalemma might be involved in its pharmacological action.
BW A575C, a chemically novel agent with angiotensin converting enzyme inhibitor and β‐adrenoceptor‐blocking properties
Authors: Allan G. , Cambridge D. , Hardy G.W. , Follenfant M.J. 
Published: July 2012

BW A575C (N‐(1‐(S)‐carboxy‐5‐[4(3‐isopropylamino‐2‐(R, S)‐hydroxypropoxy)indole‐2‐carboxamido]pentyl)‐(R, S)‐alanyl‐(S)‐proline) is a chemically novel agent which exhibits in a single molecule both angiotensin converting enzyme (ACE) inhibition and β‐adrenoceptor‐blocking properties.
BW A575C produced a competitive blockade of heart rate responses to isoprenaline in a guinea‐pig right atrial preparation (pKB 7.18 ± 0.05, cf. pindolol 8.9 ± 0.7). BW A575C inhibited a partially purified preparation of ACE obtained from rabbit lung (IC50 10.7 ± 2.1 nm, cf. enalaprilat, 4.4 ± 0.8 nm).
Intravenous administration of BW A575C (1–100 μg kg−1 min−1) to the pithed rat inhibited in a dose‐dependent fashion both angiotensin I‐induced pressor responses and isoprenaline‐induced tachycardia. Dose‐ratios obtained from such studies demonstrated that, in this preparation, BW A575C was approximately 100 times more active as an ACE inhibitor than as a β‐adrenoceptor blocking agent.
Intravenous administration of BW A575C (1 mg kg−1) to the conscious rat inhibited angiotensin I‐induced pressor responses, being approximately equipotent to enalapril and 10 times more potent than captopril. At the same dose, BW A575C had a similar duration of action as an ACE inhibitor to enalapril.
Intravenous administration of BW A575C (1 mg kg−1) to either conscious dogs or rats inhibited both angiotensin I‐induced pressor responses and isoprenaline‐induced heart rate responses. Dose‐ratios obtained from such studies demonstrated that in these species, BW A575C was 2–10 times more active as an ACE inhibitor than as a β‐adrenoceptor blocking agent.
Muscarinic activity of McN‐A‐343 and its value in muscarinic receptor classification
Authors: Eglen R.M. , Kenny B.A. , Michel A.D. , Whiting R.L. 
Published: July 2012

The affinity and potency of McN‐A‐343 (4‐(m‐chlorophenyl‐carbamoyloxy) −2‐butynyltrimethylammonium chloride) has been assessed at a range of M1 and M2 muscarinic receptors. McN‐A‐343 was shown to act as a full agonist at M2 receptors present in the guinea‐pig isolated taenia caeci (–log EC50 = 5.14). McN‐A‐343 exhibited no agonist action in the guinea‐pig ileum, atria, bladder or trachea.
McN‐A‐343 was not selective in terms of affinity since its dissociation constants at M1 and M2 binding sites in the rat cerebral cortex and myocardium respectively, were very similar (cortical pPKi = 5.05; myocardial pKi = 5.22). The selectivity previously reported for the compound may be due to differences in intrinsic efficacy and/or tissue receptor reserve.
Based on differential antagonist affinities, the muscarinic receptor profile of the taenia caeci, trachea and bladder was similar to that observed in the ileum, but dissimiliar to that observed in the atria.
Effects of dantrolene on force development in slow‐and fast‐twitch muscle of euthyroid, hypothyroid, and hyperthyroid rats
Authors: Everts M.E. , van Hardeveld C. 
Published: July 2012

The effects of dantrolene on twitch and tetanic force development were determined in soleus and gastrocnemius muscle of euthyroid, hypothyroid, and hyperthyroid rats.
Maximum twitch force of the gastrocnemius muscle was significantly more depressed by dantrolene than that of the soleus muscle in euthyroid and hyperthyroid rats. In hypothyroid rats, the effect of dantrolene on maximum twitch force was similar in soleus and gastrocnemius muscle.
Maximum tetanic force in soleus and gastrocnemius muscle was less depressed by dantrolene than the twitch force in either thyroid state. The effect of dantrolene on maximum tetanic force increased in both muscles in the direction hypothyroid → euthyroid → hyperthyroid.
The results are discussed in terms of an effect of thyroid hormones on Ca2+‐cycling during force development, as a result of thyroid hormone‐induced proliferation of the sarcoplasmic reticulum.
Comparison of the effects of indomethacin, RHC80267 and R59022 on superoxide production by 1,oleoyl‐2,acetyl glycerol and A23187 in human neutrophils
Authors: Dale M. Maureen , Penfield Adrienne 
Published: July 2012

Indomethacin (10−4 m) causes marked augmentation of O−2release from human neutrophils when these are stimulated by either 1,oleoyl‐2,acetylglycerol or the divalent cation ionophore, A23187, the concentration‐response curve for each agent being shifted to the left and the maximum response to each increased.
The diacylglycerol kinase inhibitor, R59022 (10−5 m) has effects very similar to those of indomethacin on both the 1,oleoyl‐2,acetylglycerol‐induced and the A23187‐induced concentration‐response curves for O2‐ generation.
The diacylglycerol lipase inhibitor, RHC80267 (10−5 m) on the other hand, has a similar effect to indomethacin on 1,oleoyl‐2,acetylglycerol‐induced O−2 generation but, unlike indomethacin, has no effect on A23187‐induced O−2 generation.
Comparison of the effects of these three agents provides a clue to the locus of the action of indomethacin in increasing superoxide release, suggesting that it may act as a diacylglycerol kinase inhibitor. A component of diacylglycerol lipase inhibition may also be present. It is suggested that these results could have relevance for the use of indomethacin as an anti‐inflammatory agent in chronic rheumatoid diseases.