bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of airway epithelium on smooth muscle contractility in bovine trachea
Authors: Barnes Peter J. , Cuss Francis M. , Palmer James B. 
Published: July 2012

In bovine tracheal smooth muscle the presence of airway epithelium significantly reduced the sensitivity and maximum contractile response to histamine, 5‐hydroxytryptamine (5‐HT) or acetylcholine.
Muscle contraction induced by K+ and electrical field stimulation was of similar magnitude both in the presence or absence of adherent epithelium.
The effect of epithelium on smooth muscle contractility was unaffected by pretreatment with indomethacin (10−6 M) or mepacrine (5 × 10−5 M).
The relaxant response to isoprenaline was enhanced in the presence of epithelium, although this was significant only in the case of precontraction with 5‐HT.
It is concluded that the bronchial epithelium may produce a relaxant factor which is not a cyclo‐oxygenase or lipoxygenase product. The production of this factor may be reduced or lost following epithelial damage and this may be important in the pathogenesis of bronchial hyperresponsiveness in asthma.
Neuronal muscarinic receptors attenuate vagally‐induced contraction of feline bronchial smooth muscle
Authors: Blaber L.C. , Fryer Allison D. , Maclagan Jennifer 
Published: July 2012

In anaesthetized cats, stimulation of the vagus nerves produced bradycardia and a bronchoconstriction which was measured as an increase in lung resistance (RL) and a fall in dynamic lung compliance (Cdyn); these effects were abolished by atropine.
Gallamine potentiated vagally‐mediated changes in RL and Cdyn at doses that blocked muscarinic receptors in the heart and inhibited neuromuscular transmission. (+)‐Tubocurarine and suxamethonium did not affect the response of the lung or the heart to vagal stimulation.
Bronchoconstriction induced by intravenous acetylcholine was not potentiated by gallamine, indicating that postsynaptic muscarinic receptors in the lung and changes in muscle tone were not involved.
Potentiation of vagally‐induced bronchoconstriction appears to be due to blockade of inhibitory muscarinic receptors located in the pulmonary parasympathetic nerves innervating both central and peripheral airways.
Pilocarpine was an agonist for these neuronal receptors as it inhibited vagally‐induced bronchoconstriction at low doses (10 ng to 1 μg kg−1).
The results demonstrate that gallamine is an antagonist and pilocarpine an agonist at neuronal muscarinic receptors which attenuate parasympathetic nerve activity in feline lung.
Response and sensitivity of guinea‐pig airway muscle preparations to 5‐hydroxytryptamine during ontogenesis
Authors: Bayol Anne , Benveniste Jacques , Brink Charles , Cerrina Jacques , Gateau Olivier , Labat Carlos , Raffestin Bernadette 
Published: July 2012

Responsiveness (g mm−2) and sensitivity (pD2 value) to 5‐hydroxytryptamine (5‐HT) were markedly reduced in isolated tracheal and bronchial tissues from guinea‐pigs during ontogenesis. Responsiveness of the trachea to 5‐HT was depressed much more than that to histamine.
Airway preparations from young guinea‐pigs of either sex always contracted when exposed to 5‐HT, an effect that was blocked by methysergide.
Airway muscle preparations from old animals exhibited a wide range of responses to 5‐HT, namely, no effect, relaxation or contraction.
The contractile effect of 5‐HT in tracheal and bronchial preparations from old animals was always blocked by methysergide, whereas, the relaxant effect was not.
These results indicate that there are significant alterations in the response to 5‐HT receptor stimulation in airway muscle preparations from guinea‐pigs during ontogenesis.
Mechanism of the antinociceptive action of mesaconitine: participation of brain stem and lumbar enlargement
Authors: Hikino Hiroshi , Murayama Mitsuo 
Published: July 2012

The antinociceptive action of mesaconitine (MA) microinjected into the nucleus reticularis gigantocellularis (NRGC), the nucleus reticularis paragigantocellularis (NRPG), the periaqueductal gray (PAG) or the lumbar enlargement was investigated in rats by use of the tail immersion test. In addition, the effects of β‐adrenoceptor antagonists and an α‐adrenoceptor antagonist administered intrathecally (i.t.) on the antinociceptive action of MA given into the NRPG were also examined by the tail immersion test.
MA (50, 100 ng per rat) microinjected into the NRGC, the NRPG, the PAG and the lumbar enlargement increased the response latency in rats in a dose‐dependent fashion. MA (50 ng per rat) microinjected into neighbouring sites, the nucleus reticularis parvocellularis, the nucleus originis nervi abducentis and the fasciculus longitudinalis medialis, elicited no significant effect.
Intrathecally administered propranolol (1 and 5 μg per rat), atenolol (1 and 5 μg per rat) and IPS‐339 (1 and 5 μg per rat) remarkably inhibited the increase of the response latency induced by MA (50 ng per rat) given into the NRPG.
Intrathecally administered phenoxybenzamine (1 and 5 μg per rat) inhibited the increase of the response latency induced by MA (50 ng per rat) injected into the NRPG but to a lesser extent than the β‐adrenoceptor antagonists.
It is concluded that the NRGC, the NRPG, the PAG and the lumbar enlargement are involved in the sites of the antinociceptive action of MA and that the antinociceptive effect of MA administered into NRPG is elicited by activation of the inhibitory noradrenergic neurones from the NRPG in particularly via β‐receptor‐mediated effects of noradrenaline.
Effects of chronic administration of amitriptyline or mianserin on rat cardiac and central adrenoceptors
Authors: Choudhury L. , O'Donnell J.M. 
Published: July 2012

Rats were administered either amitriptyline (20 mg kg−1, i.p.) or mianserin (10 mg kg−1, i.p.) for 21 consecutive days and the α‐ and β‐adrenoceptor characteristics of cardiac ventricles, cerebral cortex and hippocampus examined by ligand‐binding procedure.
Chronic administration of amitriptyline significantly reduced the maximum density of β‐receptors in the cerebral cortex without significantly altering cardiac α‐ or β‐receptors; mianserin treatment had no significant effect on any of the receptors studied.
Conjugated catecholamines and pressor responses to angiotensin, luteinizing hormone‐releasing hormone and prazosin in conscious toads
Authors: Wilson J.X. 
Published: July 2012

Synthetic angiotensin II (Ang II), mammalian luteinizing hormone‐releasing hormone (LHRH) and salmon LHRH (sLHRH) were injected intravenously into conscious, adult toads (Bufo marinus) to elucidate the cardiovascular actions of the hormones. The maximal increases in pulse pressure elicited by the three peptides did not differ from each other but only Ang II increased cardiac frequency. The maximal increases in mean arterial blood pressure (MAP) caused by LHRH and sLHRH were identical, while Ang II caused a 100% greater maximal effect. The median effective doses (ED50) for both Ang II and LHRH were approximately 0.1 nmol kg−1 whereas the potency of sLHRH was 10 fold less. Pressor responses to LHRH and sLHRH were blocked completely by (D‐pGlu1, D‐Phe2, D‐Trp3,6)‐LHRH but this antagonist did not inhibit Ang II.
Significant proportions of circulating, endogenous dopamine, noradrenaline (NA) and adrenaline (Ad) were found to be sulphoconjugated. Arterial plasma concentration of free NA increased simultaneously with the rise in blood pressure following Ang II injection. The magnitude of the free NA response increased with increasing Ang II dose but even a high dose failed to augment the plasma level of conjugated NA. Ang II did not alter concentrations of free or conjugated dopamine and Ad.
Intraarterial injection of an α‐adrenoceptor antagonist, prazosin, caused sustained elevation of arterial pressure and free Ad. Subsequently Ang II lowered plasma Ad concentration. Prazosin inhibited the NA response to Ang II yet the pressor effects of the α‐adrenoceptor antagonist and Ang II were additive. Administration of a β‐adrenoceptor antagonist, propranolol, largely reversed the cardiovascular sequelae of α‐adrenoceptor blockade.
It is concluded, firstly, that the cardiovascular actions of Ang II and LHRH are mediated through different receptors. Secondly, although it had been shown that α‐ and β‐adrenoceptor mechanisms mediate the pressor effect of LHRH, the present experiments showed that mobilization of catecholamines cannot account for the pressor response to Ang II. Thirdly, both free and conjugated catecholamines circulate in toads; however the extent of conjugation can be dissociated from the changes in free NA and Ad induced by Ang II and prazosin
Pre‐incubation of guinea‐pig myenteric plexus with β‐funaltrexamine: discrepancy between binding assays and bioassays
Authors: Corbett A.D. , Kosterlitz H.W. , McKnight A.T. , Paterson S.J. , Robson L.E. 
Published: July 2012

The acute effects of β‐funaltrexamine and the effects of pre‐incubation with this compound were examined in five in vitro assay tissues and in selective binding assays in homogenates of guinea‐pig brain and myenteric plexus.
In competitive displacement assays with selective ligands, β‐funaltrexamine had highest affinity for the μ‐binding site in the myenteric plexus and brain of guinea‐pig. Its affinity for the k‐site was about 15% of that for the μ‐site.
Pre‐incubation of the assay tissues with β‐funaltrexamine caused an increase in the IC50 values of μ‐and δ‐receptor agonists but not of k‐agonists. Although in bioassays on the myenteric plexus‐longitudinal muscle preparation of the guinea‐pig, the IC50 value of the μ‐receptor ligand [D‐Ala2, MePhe4, Gly‐ol5] enkephalin was increased up to 124 fold, its binding at the μ‐site in homogenates of the preparation was not affected by this treatment.
These findings indicate that the effects of pre‐incubation with β‐funaltrexamine on agonist potency of the μ‐receptor ligand are due to an interference with the coupling mechanism between the μ‐binding site and the effector system.
Comparative effects of cotrimoxazole (trimethoprimsulphamethoxazole) and spiramycin in pregnant mice infected with Toxoplasma gondii (Beverley strain)
Authors: Nguyen B.T. , Stadtsbaeder S. 
Published: July 2012

The effects of cotrimoxazole (CTX) and spiramycin (Spir) in mice infected in midpregnancy with the Beverley (Bev) strain of Toxoplasma gondii were compared.
Therapeutic effectiveness was determined according to the following parameters: rate of successful delivery, litter size, offspring weight and survival.
When compared with the uninfected untreated control group, CTX showed a more beneficial therapeutic effect than Spir, with a statistically significant increase in the rate of both successful delivery and offspring survival.
Results based on antitoxoplasma antibody determinations in the offspring indicated a better in utero control of congenital infection by CTX than by Spir.
Simultaneous measurement of contractile effects in the circular and longitudinal smooth muscle of the rat vas deferens by drugs perfused externally or via the lumen
Authors: Busatto Pedro A. , Jurkiewicz Aron 
Published: July 2012

The effects of noradrenaline and barium chloride were studied in the rat isolated vas deferens by perfusion of drugs either externally or through the lumen of the organ. Two effects were recorded simultaneously in the same preparation: (a) isometric contractions, due to the tension elicited by drugs on the external (longitudinal) smooth muscle layer and (b) pressure of internal perfusion, due to contractions of the internal (circular) smooth muscle layer.2 It was found with the longitudinal muscle that: (a) the potency, expressed as pD2 values, and the maximum response to noradrenaline were lower if the drug was perfused internally rather than externally; (b) the differences in maximum effects were pronounced on the prostatic half but were not observed on the epididymal half; (c) the maximum response obtained by internal perfusion could be increased by simultaneously adding the same dose of drug externally; (d) when barium chloride was used instead of noradrenaline no significant differences were observed on pD2 values, but differences on maximal responses were similar to that observed for noradrenaline; (e) it was possible to block completely the effect of internal or external noradrenaline on the longitudinal muscle, by perfusing external phenoxybenzamine. In these conditions the responses of the circular muscle to the agonist were only partly blocked.
With the circular muscle, the differences related to internal and external perfusion were less marked than in the longitudinal muscle. However, unlike the latter, the circular layer was slightly more sensitive to drugs applied internally, in relation to pD2 values.
It is suggested that the difference in pD2 values may be due to the removal of noradrenaline by the neuronal uptake process, whereas the difference in maximal effect is due to the inaccessibility of part of the receptor population when drugs are added through the lumen.
Effects of H1 receptor blocking drugs on the frog sartorius neuromuscular junction
Authors: Katayama Sohta , Tasaka Kenji 
Published: July 2012

The effects of H1‐receptor blocking agents, pyrilamine, promethazine, and diphenhydramine, on the amplitude and time course of endplate potentials (e.p.ps) were studied in the sartorius muscles of frogs.
H1‐receptor blockers (10−5‐10−4M) reduced the amplitude of e.p.ps recorded intracellularly without affecting the resting membrane potential.
The acetylcholine potential was decreased by perfusion of H1‐preceptor blockers. However, when the muscle fibre was stimulated directly, threshold and magnitude of action potential were not affected by H1‐receptor blockers.
The time constant of decay of the e.p.ps recorded extracellularly was reduced by H1‐receptor blockers and the decay remained exponential with a single time constant.
The quantal content was not reduced by perfusion of H1‐receptor blockers at a concentration of 10−4 M.
It is assumed that the major site of action of these H1‐receptor blocking agents is at the postsynaptic membrane.
Prostaglandin release mediates drug‐induced stimulation of sodium transport in frog skin: the effects of quinacrine
Authors: Erlij David , Gersten Lewis 
Published: July 2012

Quinacrine markedly increased the release of prostaglandin E2 (PGE2) into the basolateral solution of the bullfrog skin from a control value of 32.7 ± 21.7 pg per 20 min period to a stimulated value of 8593.1 ± 4112.3 pg per 20 min period.
Quinacrine increased the amiloride‐sensitive short circuit current from 20.7 ± 2.1 μA cm−2 to 45.4 ± 6.5 μA cm−2.
The stimulatory effects of quinacrine on both short circuit current and prostaglandin release were blocked in skins pretreated with indomethacin (10−6 M).
Quinacrine did not block either the stimulation of the short circuit current or the increase in PGE2 release caused by the calcium ionophore, ionomycin.
These results suggest: (a) the release of PGE2 and the stimulation of the short circuit current caused by quinacrine are linked since blocking PGE2 release inhibits the stimulation of the short circuit current; (b) given the complexity of its actions, quinacrine is a poor tool to examine whether the effects of a given agent are mediated through the activation of endogenous phosopholipases. In addition our results taken together with other findings in the literature suggest that there is a diverse group of compounds that stimulate transepithelial sodium transport by releasing PGE2.
Transmembrane sodium and potassium gradients modulate histamine secretion induced by ionophore A23187
Authors: Amellal M. , Bronner C. , Landry Y. 
Published: July 2012

Histamine secretion was induced from rat peritoneal mast cells by calcium ionophore A23187 in the presence of various extracellular calcium concentrations. Transmembrane sodium and potassium gradients were altered by cold pretreatment of mast cells or through the inhibition of sodium‐potassium ATPase by the use of ouabain or potassium‐deprivation.
Such pretreatments led to a parallel shift to the left of the extracellular calcium concentration‐histamine secretion curve, i.e. to an apparent decrease of extracellular calcium requirement for the ionophore‐induced histamine release.
These effects were fully reversed by warming mast cells, by washing out ouabain or by adding potassium. Metabolic inhibition of mast cells prevented the ionophore‐induced secretion in all the experimental conditions described. Secretion observed in the absence of added calcium was inhibited by short term treatment of cells with 5 times 10−6 M EGTA or EDTA provided magnesium was absent from the assay medium.
Data show that ionophore A23187 was able to induce secretion in the presence of micromolar concentrations of extracellular calcium, when the efficiency of the ionophore was not decreased by extracellular magnesium and when transmembrane sodium and potassium gradients were altered.
Platelet desensitization induced by arachidonic acid is not due to cyclo‐oxygenase inactivation and involves the endoperoxide receptor
Authors: Carmo L.G. , Hatmi M. , Rotilio D. , Vargaftig B.B. 
Published: July 2012

Human platelets pre‐exposed to arachidonic acid (AA) (0.1‐1 mM) or to the endoperoxide analogue U46619 (1–3 μM) and then washed and resuspended, failed to respond with aggregation or secretion to a second challenge by either agonist. The response to thrombin at low (0.04‐0.1 u ml−1) but not at high (2.5 u ml−1) concentrations was also inhibited by pre‐exposure to AA and U46619.
The ability of platelets to synthesize thromboxane (Tx) B2 from AA or upon challenge with thrombin persisted despite platelet desensitization.
In the presence of the reversible cyclo‐oxygenase (CO) inhibitors methyl salicylate (MS) or L8027, pre‐exposure to AA had no effect on subsequent challenge by the same agonist or by U46619, whereas platelet desensitization by pre‐exposure to U46619 persisted. However, platelet activation by, and desensitization to AA and U46619, was prevented by trimetoquinol and compound L636499, two thromboxane/endoperoxide receptor antagonists.
In contrast to the CO inhibitors, the thromboxane synthetase inhibitor dazoxiben, which in 3 ‘responders’ out of 5 subjects suppressed aggregation, secretion, and Tx formation induced by AA, failed to prevent AA‐induced desensitization.
Compared to quiescent cells the distances between platelets desensitized after re‐exposure to AA were reduced in electron microscopy, but the tight connections associated with aggregated cells were not observed. Degranulation was also not observed and cell morphology resembled that of normal quiescent platelets.
In conclusion, (a) AA and U46619 desensitize human platelets at a similar site sensitive to prostaglandin/thromboxane receptor antagonists, and show cross‐desensitization; (b) desensitization by AA appears to be mediated by a CO‐dependent metabolite, as CO inhibitors prevent desensitization by AA but not to U46619; (c) the failure of dazoxiben to prevent desensitization by AA suggests that a metabolite other than TxA2, possibly the endoperoxides, mediates the phenomenon; (d) desensitization does not involve inactivation of CO or thromboxane synthetase enzymes.
Characterization of histamine receptors mediating the stimulation of cyclic AMP accumulation in rabbit cerebral cortical slices
Authors: Al‐Gadi M. , Hill S.J. 
Published: July 2012

The characteristics of histamine‐stimulated adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) accumulation in slices of rabbit cerebral cortex have been investigated.
The selective H2‐receptor antagonists, cimetidine, tiotidine, metiamide and ranitidine appeared to antagonize the stimulation of cyclic AMP accumulation elicited by histamine in a competitive manner consistent with an interaction with histamine H2‐receptors.
The H1‐preceptor antagonist mepyramine (0.8 μM) produced only a weak inhibition of the response to histamine. The inhibition appeared to be non‐competitive producing a decrease in the maximal response with little effect on the EC50 value.
The specific H2‐receptor agonist, impromidine, produced a maximum response of only 31 ± 2% of that obtained with histamine. Studies with histamine and impromidine in combination indicated that impromidine was not acting as a partial agonist. 2‐Thiazolylethylamine, a selective H1‐agonist, produced only a weak response (EC50 ∼ lmM) yielding a relative potency with respect to histamine (= 100) of 2.5.
In the presence of a supramaximal concentration of impromidine, histamine and 2‐thiazolylethylamine further elevated the response to impromidine. In these conditions the relative potency of 2‐thiazolylethylamine was increased to 59 (histamine = 100), a value which was comparable with that reported for H1‐receptor‐mediated contractions of guinea‐pig ileum.
The H1‐receptor antagonists mepyramine, promethazine, triprolidine and chlorpheniramine competitively antagonized the potentiation of impromidine‐stimulated cyclic AMP accumulation elicited by histamine and 2‐thiazolylethylamine in rabbit cerebral cortex without affecting the response to impromidine alone. (+)‐Chlorpheniramine was some 150 fold more potent than the (—)‐isomer in this respect.
Histamine and adenosine in combination had a much greater than additive effect on the accumulation of cyclic AMP in rabbit cerebral cortical slices. The potentiation of the adenosine response could be partially but not completely antagonized by either cimetidine or mepyramine.
In the presence of H2‐receptor blockade with 0.02 mM tiotidine, histamine elicited a significant potentiation (EC50 44 μM) of the response to adenosine. This response was antagonized competitively by mepyramine yielding a KB value of 0.05 μM similar to that obtained from inhibition of the potentiation of impromidine‐stimulated accumulation of cyclic AMP (0.02 μM).
These results suggest that there are two components in the response to histamine in rabbit cerebral cortical slices. The first component appears to be mediated by histamine H2‐receptors while the second, mepyramine‐sensitive, component has some of the characteristics of an H1‐receptor mediated response and requires prior stimulation of adenosine‐ or H2‐receptors to produce its effect.
Enthalpy‐entropy relationship in drug‐cholinoceptor interaction: a new approach
Authors: Cohen Sasson , Haberman Frank 
Published: July 2012

The partial molal volume at infinite dilution, , was determined in toluene, benzene and acetonitrile for fifteen different drug molecules comprising muscarinic agonists, partial agonists and antagonists.
The difference in between a given drug, X, and hyoscine, expressed as was then multiplied by the internal pressure of the holding phase (P1 ∼ cohesive energy density) in order to obtain an estimate of the excess enthalpy (ΔH) over hyoscine in the interaction of drug molecule X with a common cholinoceptor. As a working hypothesis, ΔH for hyoscine is taken as zero, hyoscine having the lowest /affinity ratio of any drug in the series investigated.
The corresponding change in entropy (ΔS) was then calculated from the relationship: RT ln Kx= Pi, where Kx is the affinity constant of drug molecule X to the common cholinoceptor, obtained independently.
Linear regression of P1 ⋍ ΔH from the data in acetonitrile over ΔS gave a satisfactory isoequilibrium plot, r2 = 0.954, slope (β) = 231°K.
The present approach offers a new course for the study of the enthalpy‐entropy relationship in the interaction of drug molecules in a given series with a common receptor. It could provide an alternative to the Van't Hoff procedure for the estimation of relative ΔH, and is independent of the free energy of binding (ΔG).