bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contractile effects of cysteamine on the guinea‐pig ileum
Authors: Bakich V. , Brown J. , Kwok Y.N. , McIntosh C. , Nishimura E. 
Published: July 2012

Cysteamine (β‐mercaptoethylamine HCl) (1.0–40.0 mM) induced a concentration‐dependent increase in tonic and phasic contractions of segments of guinea‐pig ileum in vitro. Myenteric plexus‐longitudinal muscle (MPLM) preparations also responded with an increase in tonic contractions but phasic contractions were either greatly reduced or absent, indicating that these were a response of the circular muscle.
Atropine (5 μM) inhibited the cysteamine‐induced contractions, whereas hexamethonium and guanethidine had no effect, suggesting that cysteamine was acting at least partly via a cholinergic mechanism involving muscarinic receptors.
Tetrodotoxin increased the phasic contractions of ileal segments, but had no effect on the tonic component.
Treatment of MPLM preparations with morphine (1 μM) resulted in a small reduction in responsiveness to cysteamine, and blocked electrically‐induced contractions by at least 90%. Since morphine acts by inhibiting acetylcholine release via hyperpolarization of intrinsic neurones, a small but significant part of the cysteamine‐induced contractions probably resulted from stimulation of acetylcholine release from intrinsic neurones.
Following a response to high cysteamine concentrations (> 15 mM) tissues were refractory to subsequent cysteamine administration. Cross‐desensitization between cysteamine and acetylcholine also occurred, as short term (1–3 min) incubation of MPLM preparations with high concentrations of either compound (1–10 μM acetylcholine or 20 mM cysteamine) resulted in a reduced responsiveness to both.
A reduced sensitivity to acetylcholine or cysteamine was obtained following long‐term (45 min) incubation with acetylcholine (1 μM). Removal of Na+ from the incubation medium negated this effect. In contrast, the refractoriness to acetylcholine or cysteamine following long‐term (45 min) incubation with cysteamine (20 mM) was accentuated in low Na+ medium.
It is suggested that cysteamine induces a contraction of both the circular and longitudinal muscle of the guinea‐pig ileum by stimulating the release of acetylcholine from intrinsic neurones, by an action at the level of the smooth muscle muscarinic receptor, and possibly by a non‐cholinergic mechanism. However, the mechanisms by which acetylcholine and cysteamine induce tissue refractoriness probably differ.
α‐Adrenoceptor stimulated lymphocytes trigger the mechanical response of vas deferens: participation of arachidonic acid metabolites
Authors: Borda Enri S. , de Bracco Maria M. , Cangiani Silvia , Finiasz Marta , Sterin‐Borda Leonor 
Published: July 2012

Normal human lymphocytes (L) (8 × 105 ml−1) incubated with methoxamine (Me) (1 × 10−7 M) (Me‐L) triggered the mchanical response of the isolated vas deferens of the rat. L or Me alone did not modify this contractile activity at the concentrations cited above.
Me alone (10−6 to 10−3 M) increased the tension of the vas. In the presence of L (8 × 105 ml−1) the dose‐response curve to Me shifted to the left and the efficacy of Me was enhanced.
Inhibitors of α1‐adrenoceptors completely blocked the reaction between Me and L while drugs that block α1 and α2‐adrenoceptors reduced the reaction between Me‐L and the vas deferens.
Direct contact of Me‐L with the assay organ was not necessary. Cell‐free supernatants of L exposed to Me (Me‐L supernatants) elicited the reaction in the same way as Me‐L. This effect required the continuous presence of Me since dialyzed Me‐L supernatants were inactive.
Inhibitors of lipoxygenase(s) completely blocked the positive inotropic effect of Me‐L or of Me‐L supernatants. Inhibitors of cyclo‐oxygenase potentiated this effect.
These results suggest that Me reacts with α1‐adrenoceptors of L. From this reaction, soluble factors are released that potentiate the α‐adrenoceptor stimulatory effect of Me on the vas deferens as a consequence of the release of oxidative products of the lipoxygenase/s pathway of arachidonic acid.
The effect of fasting on 5‐hydroxytryptamine metabolism in brain regions of the albino rat
Authors: Fuenmayor Luis D. , García Susana 
Published: July 2012

The turnover of 5‐hydroxytryptamine (5‐HT) in the whole brain and different brain regions was studied in rats fasted for 24 h. These rats showed an increased tissue concentration of the amine in the whole brain and of its metabolite 5‐hydroxyindoleacetic acid (5‐HIAA) in the whole brain, the striatum, the combined pons‐medulla and the cerebral cortex.
The accumulation of 5‐HIAA after probenecid was increased by fasting in the regions mentioned above except for the striatum. The effect of probenecid was also increased by fasting in the midbrain, the hypothalamus and the hippocampus.
In the striatum, the administration of probenecid produced a smaller increase in 5‐HIAA concentration in fasted than in fed rats.
The decay of 5‐HT following p‐chlorophenylalanine (PCPA) was increased in the hypothalamus of fasted rats at 16 h, but not at 4 h, after the intraperitoneal administration of the inhibitor. In the midbrain, the striatum and the combined pons‐medulla, food deprivation did not modify the decrease induced by PCPA. However, the inhibitor induced a reduction of food consumption in the fed group, which made this group rather similar to the fasted one and complicated the interpretation of the results in these last three cerebral areas.
Our results confirm that food deprivation increases the turnover of brain 5‐HT and point out that the increase probably occurs in all brain areas. This increased tunover appears to be accompanied, in the hypothalamus, by an increased neuronal release of the amine. In the striatum, fasting probably blocks the active transport system which removes acid metabolites from the brain.
Enhancement of tetrodotoxin‐induced axonal blockade by adenosine, adenosine analogues, dibutyryl cyclic AMP and methylxanthines in the frog sciatic nerve
Authors: Ribeiro J. A. , Sebastião A.M. 
Published: July 2012

The effects of adenosine, adenosine analogues (N6‐cyclohexyladenosine (CHA), L‐N6‐phenylisopropyladenosine (L‐PIA), D‐N6‐phenylisopropyladenosine (D‐PIA), N6‐methyladenosine and 2‐chloroadenosine), adenine, inosine, hypoxanthine, cyclic AMP and its analogue the dibutyryl cyclic AMP (db cyclic AMP), and methylxanthines (theophylline, caffeine and isobutylmethylxanthine (Ibmx) on compound action potentials were investigated in de‐sheathed sciatic nerve preparations of the frog.
Adenosine and its analogues enhanced, in a concentration‐dependent manner, the inhibitory action of tetrodotoxin (TTX) on nerve conduction. The order of potencies was: CHA ⋝ D‐PIA ⋝ L‐PIA ≫ N6‐methyladenosine ⋝ 2‐chloroadenosine ≫ adenosine.
The adenosine metabolites, inosine and hypoxanthine, were inactive on TTX‐induced axonal blockade. Adenine enhanced the inhibitory action of TTX on nerve conduction, but was less effective than adenosine.
db Cyclic AMP, but not cyclic AMP, mimicked the inhibitory effect of adenosine on nerve conduction.
Methylxanthines did not antagonize the effect of adenosine on TTX‐induced axonal block and in high concentrations also mimicked the effect of adenosine on nerve conduction.
The possibility of adenosine acting on TTX‐induced axonal block through an adenosine receptor positively coupled to adenylate cyclase is discussed.
Effects of raubasine stereoisomers on pre‐ and postsynaptic α‐adrenoceptors in the rat vas deferens
Authors: Demichel Patricia , Roquebert Jacques 
Published: July 2012

The actions of raubasine, tetrahydroalstonine and akuammigine were studied on pre‐ and postsynaptic α‐adrenoceptors of the rat vas deferens.
These three drugs competitively antagonized the effect of noradrenaline on postsynaptic α‐adrenoceptors, yielding pA2 values of 6.57, 4.56 and 4.68 respectively.
The presynaptic α‐adrenoceptor antagonist activity of the drugs was quantitatively determined by studying the effect of increasing concentrations on the clonidine dose‐response curve in the electrically stimulated vas deferens.
The inhibitory effect of clonidine could be competitively blocked by these three compounds and the pA2 values for raubasine, tetrahydroalstonine and akuammigine were 6.02, 7.71 and 5.64 respectively.
These results indicate that: akuammigine is a very weak antagonist at pre‐ and postsynaptic sites; raubasine acts preferentially at postsynaptic sites; tetrahydroalstonine is a highly selective presynaptic α‐adrenoceptor blocking agent. The ratio of the pre/postsynaptic potency declines in the order tetrahydroalstonine > akuammigine > raubasine.
Effects of serum albumin, indomethacin and histamine H1‐antagonists on Paf‐acether‐induced inflammatory responses in the skin of experimental animals and man
Authors: Archer C.B. , MacDonald D.M. , Morley J. , Page C.P. , Paul W. , Sanjar S. 
Published: July 2012

Cutaneous responses to synthetic platelet activating factor (Paf‐acether) have been studied in guinea‐pig and human skin.
Intradermal injection of Paf‐acether elicited an acute inflammatory response in guinea‐pig skin (assessed by means of radioisotopic techniques) and acute oedema formation in human skin (assessed by means of weal volume and flare area).
Acute inflammatory responses in guinea‐pig and human skin are potentiated by the presence of serum albumin, a phospholipid carrier.
Acute inflammatory responses induced by Paf‐acether in guinea‐pig and human skin are not significantly affected by concomitant administration of the cyclo‐oxygenase inhibitor, indomethacin.
Acute inflammatory responses induced by Paf‐acether in guinea‐pig and human skin are slightly modified by the H1‐receptor antagonists, mepyramine and chlorpheniramine.
These results indicate that the acute inflammatory response induced by Paf‐acether is independent of cyclo‐oxygenase products of arachidonic acid and that histamine release has a minor contribution to the inflammatory response induced by Paf‐acether.
Inhibition of tolbutamide metabolism by substituted imidazole drugs in vivo: evidence for a structure‐activity relationship
Authors: Back D.J. , Tjia J.F. 
Published: July 2012

Tolbutamide has been used as a model drug for an examination of the effects of eleven substituted imidazole compounds on hepatic metabolism in vivo.
The 1‐substituted compounds 1‐methylimidazole, miconazole, clotrimazole and ketoconazole produced marked alterations in tolbutamide kinetics (increased half‐life, decreased clearance). However, if there was substitution in the 2‐ position, irrespective of a substituent on N‐1, then the compound did not appear to inhibit metabolism (e.g. 2‐methylimidazole, 1,2‐dimethylimidazole, methimazole, metronidazole). The 4‐ substituted compounds, 4‐methylimidazole and cimetidine were inhibitors.
A structure‐activity relationship for the inhibitory actions of the substituted imidazoles is thus evident in vivo.
Ketamine‐inhibition of calcium‐induced contractions in depolarized rat uterus: a comparison with other calcium antagonists
Authors: Calixto João B. , Loch Sirley 
Published: July 2012

The inhibitory effect of the intravenous anaesthetic ketamine on CaCl2‐induced contractions in the isolated K+‐depolarized uterus of the rat in Ca2+‐free medium was compared with that produced by papaverine, theophylline and the calcium entry blocker verapamil.
Pre‐incubation for 20 min with either ketamine (0.3 to 3 mM), papaverine (3 to 30 μM), theophylline (0.1 to 1 mM) or verapamil (3 to 30 nM) induced parallel, concentration‐dependent rightward displacements of the dose‐response curves to Ca2+ (0.04 to 22 mM). The antagonism was competitive, except that due to verapamil, the Schild plot for which yielded a slope which differed significantly from unity. The calculated pA2 values (± s.e.mean) were: ketamine 3.90 ± 0.07; papaverine 5.55 ± 0.05; theophylline 3.99 ± 0.1 and verapamil 9.54 ± 0.24
These drugs differed in their ability to relax the sustained contraction induced by Ca2+ (1 mM) in K+‐depolarizing solution. Ketamine and verapamil relaxed the preparation in a concentration‐dependent manner whereas theophylline and especially papaverine were less potent and induced only partial maximal relaxation. The t1/2 of the relaxant effect was significantly less for ketamine than for verapamil (5 and 22 min, respectively). Only ketamine produced a relaxation comparable to that obtained by washing the preparation with Ca2+‐free solution (t1/2 = approx. 5 min).
Prior exposure of the depolarized uterine strip to a low concentration of Ca2+ (0.22 mM) increased the potency of ketamine, but decreased that of papaverine and theophylline, in antagonizing Ca2+‐induced contractions. In contrast, this procedure did not affect the potency of verapamil.
The inhibitory effects of these drugs, excluding those of verapamil, were completely reversed after washing the preparations with a high‐potassium Ca2+‐free solution, 3–5 times for about 30–60 min.
These experiments provide further evidence that the relaxant effect produced by ketamine on the rat isolated uterus is due to its ability to antagonize Ca2+ movements competitively and also show that there are marked differences between the nature of the relaxant effects of ketamine and those of papaverine, theophylline and verapamil.
Pharmacological characterization of the histamine receptor in the isolated muscularis mucosae of the guinea‐pig oesophagus
Authors: Fujinuma Sachie , Kamikawa Yuichiro , Shimo Yasuo 
Published: July 2012

To characterize the histamine receptors in the muscularis mucosae, the isotonic responsiveness of the isolated muscularis mucosae of the guinea‐pig oesophagus to histamine receptor agonists and antagonists was examined in vitro.
Histamine (0.1–100 μM) produced a concentration‐dependent contraction of the muscularis mucosae (EC50 = 1.6 ± 0.2 μM). The contractions were rapid in onset, sustained, reversible by washing and the preparation did not show tachyphylaxis.
2‐Methylhistamine (2‐MH), 2‐pyridylethylamine (PEA) and 4‐methylhistamine (4‐MH) produced similar sustained contractions of the muscularis mucosae. The order of sensitivity was histamine > 2‐MH > PEA > 4‐MH. Impromidine (10–300 μM) and dimaprit (10–300 μM) caused no response in this tissue.
The contractile responses to histamine, 2‐MH, and PEA were competitively antagonized by diphenhydramine, and the pA2 values were almost the same (approximately 8.1). Cimetidine (100 μM) could not modify the contractile response to these agonists.
The contractile response to histamine was slightly inhibited by tetrodotoxin (0.3 μM), atropine (1 μM), indomethacin (0.1–3 μM) or aspirin (30–300 μM), and the EC50 value was increased about 2–6 times by these drugs.
When the preparation was incubated in Tyrode solution containing various calcium concentrations (0, 0.45, 0.9 and 1.8 mM), the concentration‐response curve to histamine was shifted to the right and downward; the effect was inversely dependent on the calcium concentration, and in a calcium‐free medium the response to histamine was abolished. Verapamil (1–10 μM) partially inhibited the contractile response to histamine.
The present results indicate that the contraction of the guinea‐pig oesophageal muscularis mucosae to histamine is mediated mainly by a direct action on the smooth muscle and partly by indirect actions via the stimulation of either endogenous prostaglandin biosynthesis or intramural cholinergic nerves. The histamine receptors responsible for contractions of this tissue are probably mainly of the H1‐subtype with H2‐receptors having a negligible role.
Modulation by endothelium of contractile responses in rat aorta in absence and presence of flunarizine
Authors: Miller R.C. , Stoclet J.‐C. 
Published: July 2012

The possible modulation by endothelium of phenylephreine‐ and prostaglandin F2α‐induced mobilization of calcium for contraction in the rat aorta has been investigated. Contractions elicited by these and other agonists are inhibited in the presence of endothelium.
For any single concentration of phenylephrine in the presence of endothelium, the initial phasic components of contractions were significantly greater, the maximal contractions were achieved sooner and were less well maintained as compared to contractions elicited in the absence of endothelium.
The kinetic characteristics of contractions stimulated by single concentrations of PGF2α were similar in the presence and absence of endothelium and did not exhibit initial phasic components of contraction.
Sub‐maximal contractions elicited by both PGF2α and phenylephrine in the absence of endothelium were inhibited to a greater extent by flunarizine 3 μM than equieffective contractions elicited in the presence of endothelium.
Maximal contractions elicited by phenylephrine (1 μM) were inhibited to a similar extent by flunarizine in the presence and absence of endothelium, but maximal contractions elicited by PGF2α (30 μM) were inhibited by flunarizine to a greater extent in the presence than in the absence of endothelium.
It is concluded that an endothelium‐derived factor, perhaps distinct from endothelium‐derived relaxing factor, can modulate the ability of both phenylephrine and PGF2α to mobilize calcium for contraction. This modulatory effect is associated with an enhanced mobilization of intracellular calcium. Thus, submaximal concentrations of both agonists were less dependent on extracellular calcium than on intracellular calcium to elicit contractions in the presence of endothelium, as compared to contractions elicited in the absence of endothelium.
Potentiation by cholinoceptor agonists of contractions to field stimulation of rat vas deferens
Authors: Lee Chi‐Ming 
Published: July 2012

Cholinoceptor agonists (arecoline > carbachol > acetylcholine > pilocarpine) potentiated contractions to field stimulation of rat vas deferens via the activation of an atropine‐sensitive muscarinic receptor.
The potentiating effect of carbachol was dependent on the level of calcium in the medium, being more potent at higher calcium concentrations.
The potentiating effect of carbachol was more pronounced in the epididymal than in the prostatic segment but was not attenuated by prazosin, an α1‐adrenoceptor antagonist.
Carbachol did not significantly modify the direct contractile effects of noradrenaline nor alter the field‐stimulation‐evoked release of noradrenaline from the epididymal vas deferens.
It is concluded that the potentiating effect of cholinoceptor agonists on the contractions to field stimulation in the rat vas deferens was not a result of an enhancement of adrenergic neurotransmission.
Carbenoxolone and deglycyrrhized liquorice have little or no effect on prostanoid synthesis by rat gastric mucosa ex vivo
Authors: Bennett Alan , Melhuish Pauline B. , Stamford Ian F. 
Published: July 2012

Rats were given either carbenoxolone 50 mg kg−1, deglycyrrhized liquorice 1 g kg−1 or vehicle by gastric tube. The doses were repeated 16 h later, and the stomachs removed after another 2 h.
The amounts of prostaglandin E (PGE), 6‐keto‐PGF1α and thromboxane B2, measured by radioimmunoassay in extracts of the gastric corpus and antrum mucosa, were similar in the treated animals and the controls.
We conclude that in rats, carbenoxolone and deglycyrrhized liquorice may exert their anti‐ulcer effect by a non‐prostaglandin mechanism. This contrasts with the mechanism thought to occur in man with carbenoxolone.
A comparison of 5‐hydroxytryptamine receptors mediating contraction in rabbit aorta and dog saphenous vein: evidence for different receptor types obtained by use of selective agonists and antagonists
Authors: Feniuk W. , Humphrey P.P.A. , Perren M.J. , Watts A.D. 
Published: July 2012

Using recently available selective agonists and antagonists we have examined further our postulate (Apperley et al., 1980) that 5‐hydroxytryptamine (5‐HT) mediates contraction of dog saphenous vein via a different 5‐HT receptor type from that in the rabbit aorta.
In the rabbit isolated aorta, ketanserin and spiperone were potent, specific, competitively‐acting antagonists of the contractile effects of 5‐HT.
In contrast, in the dog isolated saphenous vein neither ketanserin nor spiperone caused any rightward displacement of concentration‐response curves to 5‐HT although the maximum response was reduced by about 10%.
In the rabbit aorta 5‐carboxamidotryptamine (5‐CONH2‐T) was a weak agonist whilst the 5‐N,N‐dimethyl and 5‐N‐ethyl derivatives were even weaker or inactive. The contractile effect of 5‐CONH2‐T in the rabbit aorta was potently and competitively antagonized by ketanserin.
In contrast, in the dog saphenous vein 5‐CONH2‐T and its 5‐N,N‐dimethyl and 5‐N‐ethyl derivatives were all potent agonists. The contractile effect of 5‐CONH2‐T was not markedly affected by ketanserin.
The profile of action of ketanserin and spiperone in the rabbit aorta is consistent with the view that 5‐HT2 receptors mediate contraction in this preparation. However, the 5‐HT receptor mediating contraction in the dog saphenous vein appears to be ‘5‐HT1‐like’, sharing a number of characteristics with the 5‐HT1 recognition site identified from [3H]‐5‐HT ligand binding studies in brain tissue. tissue.
Evidence for two mechanisms of depolarization associated with α1‐adrenoceptor activation in the rat anococcygeus muscle
Authors: Byrne N.G. , Large W.A. 
Published: July 2012

Membrane potential responses in the rat isolated anococcygeus to bath‐applied noradrenaline and field stimulation have been investigated by use of intracellular microelectrode and combined extracellular electrical and mechanical (sucrose gap) recording techniques. Intracellular recordings were made usually from tissues immobilized with hypertonic Krebs solution.
Bath‐application of noradrenaline produced depolarizations which consisted of two components; an initial ‘fast’ phase which peaked within 1–2 s and which was followed by a ‘slow’ sustained depolarization. Both components were concentration‐dependent.
Noradrenaline could also evoke oscillations in membrane potential which, unlike the ‘fast’ component of depolarization, were prevented by conditioning hyperpolarization of the membrane and were evoked by direct membrane depolarization with externally applied current pulses. Thus, the oscillations are voltage‐dependent phenomena.
Replacement of the external NaCl of the Krebs solution with an equimolar amount of Na benzenesulphonate abolished the noradrenaline‐evoked ‘fast’ depolarization while the ‘slow’ phase was unaffected. This suggests that two mechanisms of depolarization are activated in this muscle by the bath‐application of noradrenaline. The adrenergic excitatory junction potential was also abolished in Na benzenesulphonate.
Prazosin reduced both the ‘fast’ and ‘slow’ components of depolarization produced by noradrenaline indicating their mediation by α1‐adrenoceptors.
The membrane potential (‐ 29 mV) at the maximum amplitude of the ‘fast’ depolarization was similar to the equilibrium potential (‐ 27 mV) for the depolarization evoked by ionophoretically applied noradrenaline and which was obtained by extrapolation from the relationship between amplitude of the ionophoretic response and membrane potential displacement in the partition chamber. These results suggest that the ‘fast’ depolarization and the ionophoretic response are due to an increased membrane conductance, possibly to chloride.