bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammatory actions of platelet activating factor (Paf‐acether) in guinea‐pig skin
Authors: Morley J. , Page C.P. , Paul W. 
Published: July 2012

Cutaneous responses to synthetic platelet activating factor (Paf‐acether) have been studied in guinea‐pigs by means of radioisotopic marker techniques.
Intradermal injection of Paf‐acether elicited increased plasma protein extravasation (IPPE) (0.2–200 pmol/site), platelet accumulation (PA) (20–200 pmol/site) and red blood cell accumulation (RBCA) (200 pmol/site), whereas lyso‐Paf (up to 2 nmol/site) was inactive in all these respects.
Following intradermal injection, the IPPE responses to Paf‐acether (2 and 20 pmol/site) were complete within 15 and 30 min respectively, although in response to 200 pmol/site, IPPE was detectable up to 1.5 h. The PA and RBCA responses to Paf‐acether (200 pmol/site) were complete within 1 h.
IPPE induced by Paf‐acether (3 pmol/site) was potentiated by concomitant intradermal injection of a cutaneous vasodilator prostaglandin E2 (PGE2, 1 nmol/site) and inhibited by the β‐adrenoceptor agonist, isoprenaline (4.5 nmol/site) or the α‐adrenoceptor agonist, phenylephrine (6 nmol/site). Such observations are consistent with Paf‐acether effecting increased vessel wall permeability.
Intradermal injection of PGEx (3 nmol/site) significantly reduced PA in response to Paf‐acether (200 pmol/site), whilst significantly enhancing IPPE. This dissociation of increased vascular permeability from PA is consistent with Paf‐acether eliciting IPPE via a platelet‐independent mechanism.
These results indicate that a direct effect on vessel wall permeability contributes to the inflammatory response to Paf‐acether in guinea‐pig skin. It is suggested that Paf‐acether is a potential mediator of allergy and inflammation.
Compared myocardial and vascular effects of captopril and dihydralazine during hypertension development in spontaneously hypertensive rats
Authors: Freslon J.L. , Giudicelli J.F. 
Published: July 2012

When administered to young spontaneously hypertensive rats (SHRs), dihydralazine (25 mg kg−1, daily) and captopril (100 mg kg−1, daily) prevent with the same efficacy genetic hypertension development (GHD).
Dihydralazine treatment increased vascular mesenteric compliance, as shown by a significant decrease in the stiffness of the vessels (‐27%), and induced slight reductions in contractility (‐12%) and in wall to lumen (W/L) ratio (‐15%). After treatment withdrawal, all these parameters returned to control values within 7 weeks, as did blood pressure.
Captopril treatment also strongly increased the mesenteric vessels compliance, vessel stiffness being decreased by 16%, and reduced their contractility (‐15%) and their W/L ratio (—30%). These effects as well as those exerted on blood pressure persisted up to 7 weeks after treatment ceased although there was a slight trend to a progressive reduction in the intensity of both phenomena.
These experiments show that captopril but not dihydralazine has a long‐lasting effect in opposing the functional and morphological vascular alterations occurring during GHD in SHRs and this phenomenon probably contributes to a large extent to the sustained preventive effects of the drug against GHD.
Effects of modification of the membranes of intact erythrocytes on the anti‐haemolytic action of chlorpromazine
Authors: Born G.V.R. , Housley G.M. 
Published: July 2012

Fresh human erythrocytes were washed and incubated at 37°C in physiological saline buffered with Tris, containing calcium and either neuraminidase or trypsin or both enzymes together.
Each enzyme alone, as well as both together, released similar amounts of sialic acids without haemolysis, apparently therefore from the same accessible sites on the surface of the cells.
Exposure to neuraminidase or/and trypsin did not affect the osmotic fragility of red cells in hypotonic saline.
The anti‐haemolytic effect of low concentrations of chlorpromazine or thioridazine was diminished by previous exposure of red cells to neuraminidase and/or trypsin. The diminution in the anti‐haemolytic effect of chlorpromazine was proportional to the release of sialic acids.
The observations suggest that positively charged drugs such as chlorpromazine interact strongly with the negatively charged sialic acid moieties of glycoproteins on cell surfaces, removal of which increases the drugs' access to and disruption of the lipid bilayer in cell membranes.
Endothelium‐dependent relaxation of the pig aorta: relationship to stimulation of 86Rb efflux from isolated endothelial cells
Authors: Gordon John L. , Martin William 
Published: July 2012

Bradykinin, adenosine triphosphate (ATP) and acetylcholine each relaxed histamine‐contracted strips of pig aorta in a dose‐dependent manner. These relaxations were abolished when the endothelium was removed.
Relaxation induced by ATP was mimicked by adenosine diphosphate (ADP) but adenosine monophosphate (AMP) and adenosine were about 120 times less potent.
Relaxation induced by acetylcholine was antagonized by atropine in a competitive manner, and carbachol induced the same degree of relaxation as acetylcholine, but was about 10 times less potent.
The calcium ionophore, A23187, also induced a dose‐dependent relaxation of pig aortic strips provided the endothelium was present, suggesting that a rise in the level of ionized calcium within the endothelial cells is one means by which vascular smooth muscle relaxation can be triggered.
Bradykinin, ATP, ADP, AMP, adenosine and A23187 each induced a dose‐dependent increase in 86Rb efflux from preloaded pig aortic endothelial cells. The dose‐response curves for stimulation of 86Rb efflux and for endothelium‐dependent relaxation were similar for each individual compound. ADP was equipotent with ATP, but AMP and adenosine were about 120 times less potent.
Neither acetylcholine nor carbachol, in concentrations that induce endothelium‐dependent relaxation, had any effect on 86Rb efflux from isolated aortic endothelial cells.
Lanthanum, which blocks calcium influx, abolished the increases in 86Rb efflux induced by bradykinin and ATP, and the calcium ionophore A23187 was the most effective stimulant of 86Rb efflux, suggesting that the potassium transport induced by these agents is calcium‐activated.
It is concluded that endothelial responses to bradykinin and ATP can be assessed by monitoring 86Rb efflux, which probably reflects a calcium‐activated efflux of potassium associated with the endothelium‐dependent vascular relaxation induced by these agents. This pathway is apparently not involved in endothelial responses to acetylcholine.
Coexistence of GABAA and GABAB receptors on Aδ and C primary afferents
Authors: Désarmenien Michel , Feltz Paul , Occhipinti Guiseppe , Santangelo Francesca , Schlichter Remy 
Published: July 2012

Intracellular recordings from adult rat dorsal root ganglion neurones were performed in vitro and the coexistence of two γ‐aminobutyric acid (GABA) receptors on the membrane of identified Aδ and C primary afferents was demonstrated.
Transient applications of GABA (10−6 − 10−2m) evoked dose‐dependent depolarizations and increased membrane conductance. The responses were mimicked by muscimol, isoguvacine, THIP and 3 amino propane sulphonic acid (3 APS); they were blocked by bicuculline and picrotoxin. Pentobarbitone induced an increase of GABA‐induced depolarizations.
Perfusion of tetraethylammonium (TEA, 7.5 mm) and intracellular injection of Cs+ ions unmasked the Ca2+ component of action potentials, which appeared as long‐lasting plateau depolarizations. Such action potentials were shortened in the presence of methoxyverapamil (D600, 5 × 10−6‐ 10−5m) and in a medium without Ca+ ions.
Prolonged (5–10 min) perfusion of GABA (10−9‐10−5m) shortened the Ca2+ component of action potentials. This effect was mimicked by baclofen (10−7‐5 × 10−6m) and muscimol (5 × 10−7‐10−5m) and was not affected by bicuculline perfusion (5 × 10−6‐10−5m). Isoguvacine (2.5 × 10−5m) did not affect action potential duration.
It is concluded that two GABA receptors coexist on the membrane of slow conducting primary afferents: the bicuculline‐sensitive GABAA receptor mediates depolarizations and the bicuculline‐insensitive GABAB receptor shortens the calcium component of action potentials.
Nitroglycerine‐induced biphasic relaxation in vascular smooth muscle of rat aorta
Authors: Karaki H. , Murakami K. , Nakagawa H. , Urakawa N. 
Published: July 2012

Nitroglycerine induced biphasic relaxation in the rat aorta, previously contracted by noradrenaline; a rapid decrease in tension was followed by a gradual increase reaching a steady level below the control contractile tension. No initial transient relaxation was induced by nitroglycerine in high K‐stimulated muscle.
The initial transient relaxation, but not the sustained relaxation, was dependent on the concentration of external K; maximum relaxation was observed in the presence of 2.7 mm K solution and only a slight relaxation was observed in 0 mm or 10.8 mm K solution. The initial transient relaxation was also inhibited by ouabain or low Na solution.
On an appropriate increase in the concentration of external K, noradrenaline‐induced contraction was transiently relaxed. Previous application of nitroglycerine potentiated this K‐induced relaxation.
Pretreatment of the muscle with methylene blue, an inhibitor of guanylate cyclase, inhibited both the initial transient and the sustained relaxations induced by nitroglycerine, but not the K‐induced transient relaxation.
It is suggested that the nitroglycerine‐induced initial transient relaxation, but not the sustained relaxation, may be due to a stimulation of an electrogenic Na pump. Both relaxation phases may be mediated by cyclic GMP.
Antagonism of Ca2+ and other actions of verapamil in guinea‐pig isolated trachealis
Authors: Foster R.W. , Okpalugo B.I. , Small R.C. 
Published: July 2012

In trachealis bathed by a K+‐rich, Ca2+‐free physiological salt solution, calcium chloride (CaCl2) at 0.01 to 10 mmol l−1 evoked concentration‐dependent spasm. Verapamil (0.1 to 10 μmol l−1) was an effective antagonist of CaCl2.
Spasm evoked by acetylcholine, histamine, potassium chloride (KCl) and tetraethylammonium (TEA) was studied in trachealis bathed by normal Krebs solution. Verapamil (0.1 to 10 μmol l−1) markedly suppressed spasm evoked by KCl and TEA. In contrast the actions of acetylcholine and histamine were much less affected by verapamil.
Spasm evoked by prostaglandin E2 was studied in trachealis bathed by Krebs solution containing indomethacin (2.8 μmol l−1). Verapamil (0.1 to 10 μmol l−1) had little or no effect against prostaglandin E2‐induced spasm.
Verapamil (0.1 to 10 μmol l−1) had relatively little effect on the tone of trachealis bathed by normal Krebs solution. In contrast bathing in Krebs solution lacking CaCl2 caused almost complete tone loss.
Extracellular electrophysiological recording showed that verapamil (10 μmol l−1) suppressed not only TEA‐evoked spasm but also TEA‐evoked slow waves and spike potentials. Verapamil also abolished the transient period of slow wave activity associated with the spasm evoked by KCl.
Intracellular electrophysiological recording showed that TEA‐induced spike activity was resistant to tetrodotoxin (3 μmol l−1). However, verapamil (10 μmol l−1) abolished the tetrodotoxin‐resistant spikes without increasing the resting membrane potential.
It is concluded that verapamil suppresses TEA‐ or KCl‐induced spasm, slow waves or spikes by inhibition of Ca2+ influx. Spasm evoked by acetylcholine, histamine and prostaglandin E2 depends on mechanisms for increasing the cytoplasmic concentration of free Ca2+ which are resistant to verapamil. The failure of verapamil markedly to depress tissue tone is consistent with the proposal that tone results from the activity of endogenous prostaglandins.
Evidence that the P1‐purinoceptor in the guinea‐pig taenia coli is an A2‐subtype
Authors: Burnstock Geoffrey , Hills Judith M. , Hoyle Charles H. V. 
Published: July 2012

The effects of 5′‐N‐ethylcarboxamidoadenosine (NECA), l‐NECA, 2‐chloroadenosine, N6‐phenylisopropyladenosine (l‐PIA and d‐PIA), cyclohexyladenosine (CHA), and adenosine were examined on the guinea‐pig taenia coli.
All the analogues except l‐NECA caused relaxations; the order of potency for the series was: NECA > 2‐chloroadenosine > l‐PIA > CHA > d‐PIA > adenosine.
l‐PIA was twice as potent as d‐PIA in inducing relaxations of the guinea‐pig taenia coli.
Adenosine and its analogues that induce relaxation all caused a slow membrane hyperpolarization; differences in the rates of hyperpolarization and latencies were apparent, although not statistically significant.
The duration of the response to adenosine was significantly less than that for any adenosine analogue.
Ion studies, using the sucrose gap, revealed that responses to the analogues were attenuated in elevated extracellular potassium or reduced extracellular chloride.
8‐Phenyltheophylline, a potent P1‐purinoceptor antagonist, caused a rightward shift of all the adenosine and analogue concentration‐response curves.
Dipyridamole, an adenosine uptake inhibitor, potentiated the relaxations to adenosine but had no significant effect on the relaxations induced by the analogues.
It is concluded that NECA, 2‐chloroadenosine, l‐PIA, CHA, d‐PIA and adenosine mediate their relaxant effects via an extracellular P1‐purinoceptor which displays characteristics of the A2‐subtype as determined by the rank order of agonist potency. Electrophysiological analysis of the responses to each of the analogues did not reveal any marked differences in the modes of action even between NECA and l‐PIA (preferential A2‐and A1‐receptor agonists, respectively).
Is Ro 03–7894 an irreversible antagonist at β‐adrenoceptor sites?
Authors: Krstew E. , MCPherson G. A. , Malta E. , Molenaar P. , Raper C. 
Published: July 2012

Ro 03–7894 (0.6 mm) produced a non‐parallel shift to the right of dose‐response curves to (‐)‐isoprenaline in K+ depolarized uterine preparations from the guinea‐pig. The displacement of the curves was readily reversed by washing. A rightward shift of similar magnitude was also produced by Ro 03–7894 in transmurally stimulated ileal preparations. The relaxant effects of fenoterol in carbachol‐contracted guinea‐pig tracheal preparations (in the presence of 2 μm atenolol) were not altered by 0.6 mm Ro 03–7894. In the three tissues there was no evidence of a reduction in the maximal inhibitory response to the agonists.
In uterine and tracheal preparations, Ro 03–7894 (0.6 mm) depressed contractile responses to exogenous calcium. The depression of responses was enhanced after washout of Ro 03–7894 for 80 min. Contractile responses of ileal preparations to transmural stimulation were also depressed by Ro 03–7894.
Concentration‐effect curves for the positive inotropic effects of (‐)‐isoprenaline in guinea‐pig left atrial preparations were markedly shifted to the right and the maximum response depressed by 0.6 mm Ro 03–7894. Although the rightward shift of the curves was fully reversed during the 120 min washout period, the maximal responses remained depressed. In similar experiments, Ro 03–7894 produced a washout‐resistant depression of inotropic responses to histamine and calcium.
The results of radioligand binding studies in left atria using (‐)‐[125I]‐iodocyanopindolol indicated that, when compared to the untreated atria, there was no reduction in the maximal density of binding sites 120 min after washout of 0.6 mm Ro 03–7894.
On the basis of the present results it is concluded that Ro 03–7894 induces a non‐specific depressant effect on smooth and cardiac muscle preparations during exposure to the drug. This depressant effect persists following washout of the drug. There is no evidence for an irreversible effect of Ro 03–7894 at β‐adrenoceptor sites.
An investigation of presynaptic α‐adrenoceptor subtypes in the pithed rat heart and in the rat isolated vas deferens
Authors: Docherty James R. 
Published: July 2012

The presynaptic cardio‐inhibitory effects of the α‐adrenoceptor agonists xylazine, cirazoline and amidephrine and their interaction with the antagonists yohimbine and prazosin were investigated in the pithed rat.
The presynaptic inhibitory effects of the α2‐selective agonist xylazine were antagonized by the α2‐antagonist yohimbine but not by the α2‐antagonist prazosin, thus demonstrating the lack of α2‐adrenoceptor antagonism by prazosin.
The presynaptic inhibitory effects of cirazoline were antagonized equally by yohimbine and prazosin, and the presynaptic inhibitory effects of the selective α1‐agonist amidephrine were antagonized by prazosin more potently than by yohimbine.
In the nifedipine‐treated isolated epididymal portion of the rat vas deferens, both xylazine and amidephrine produced concentration‐dependent inhibition of the isometric contraction to single pulse electrical stimulation. The α2‐antagonist rauwolscine antagonized the inhibitory effects of xylazine but not of amidephrine.
It is concluded that inhibitory α1‐adrenoceptors, as well as the already established α2‐receptors, are present presynaptically in the pithed rat heart and in the rat vas deferens.
Mechanisms of reflex bradycardia and hypotension by metabolites of arachidonic acid in the cat
Authors: Hintze Thomas H. , Kaley Gabor , Panzenbeck Maret J. 
Published: July 2012

In the cat, intravenous injections of arachidonic acid or prostaglandin (PG)F2α caused significant reductions in mean arterial pressure and heart rate which were eliminated or significantly lessened, respectively, by previous administration of indomethacin. The bradycardia to intravenous prostacyclin (PGI2) was unaffected by indomethacin.
In cats with bilateral ligation of the carotid arteries to eliminate competition between systemic baroreflexes and cardiopulmonary reflexes, PGI2, PGF2α and arachidonic acid caused significantly greater hypotension and bradycardia than in cats with intact carotid baroreflexes.
The bradycardia to PGI2, PGF2α and arachidonic acid was eliminated by bilateral vagal section or atropine.
PGE1, PGE2 and nitroprusside caused dose‐related falls in mean arterial pressure and a small tachycardia.
In a small group of cats (7 of 67) nitroprusside also caused a reduction in heart rate which was eliminated by indomethacin.
We conclude that the reflex bradycardia to PGF2α, like that to arachidonic acid is, at least in part, the result of the stimulation of synthesis of another prostaglandin, most likely PGI2.
Effect of nonselective and selective inhibitors of monoamine oxidases A and B on pethidine toxicity in mice
Authors: Boden R. , Botting Regina , Coulson P. , Spanswick Gillian 
Published: July 2012

The LD50 of pethidine was determined in mice pretreated (4 h) either with the nonselective monoamine oxidase (MAO) inhibitor, phenelzine or with clorgyline, a selective inhibitor of MAO A or deprenyl, a selective inhibitor of MAO B.
Phenelzine or combined clorgyline plus deprenyl pretreatments decreased pethidine LD50.
Clorgyline or deprenyl alone did not affect pethidine toxicity.
Whole brain 5‐hydroxytryptamine (5‐HT) concentrations were measured in the pretreated mice. 5‐HT levels were approximately doubled (P < 0.001) after phenelzine or clorgyline plus deprenyl treatment, but not after clorgyline or deprenyl given alone.
These results indicate that both MAO A and MAO B need to be inhibited to increase pethidine toxicity and brain 5‐HT levels. They support the involvement of 5‐HT in the toxic interaction between pethidine and MAO inhibitors.
Some pharmacological and biochemical interactions of the enantiomers of adenylyl 5′‐(β, γ‐methylene)‐diphosphonate with the guinea‐pig urinary bladder
Authors: Cusack N.J. , Hourani S.M.O. 
Published: July 2012

Adenosine 5′‐triphosphate (ATP) and adenylyl 5′‐(β,γ methylene)‐diphosphonate (AMP‐PCP) both contracted the guinea‐pig urinary bladder, but the response to AMP‐PCP was much greater. We synthesized the enantiomer of AMP‐PCP, L‐adenylyl 5′‐(β,γ‐methylene)‐diphosphonate (L‐AMP‐PCP), and tested it on the guinea‐pig bladder.
L‐AMP‐PCP contracted the guinea‐pig bladder, and was more potent than AMP‐PCP and much more potent than ATP. The potential breakdown product of L‐AMP‐PCP, L‐adenosine, unlike adenosine (the breakdown product of AMP‐PCP), did not inhibit contractions of the guinea‐pig bladder.
ATP and its enantiomer L‐adenosine 5′‐triphosphate (L‐ATP) were rapidly degraded by the muscle, and AMP‐PCP was also degraded, but more slowly. L‐AMP‐PCP, however, was completely resistant to degradation.
L‐AMP‐PCP would appear to be a useful ATP analogue, as it is potent and resistant to degradation, and its potential breakdown product, L‐adenosine, is inactive.
Purine involvement in morphine antinociception
Authors: Mantegazza Paolo , Tammiso Remigio , Zambotti Fernanda , Zecca Luigi , Zonta Nerina 
Published: July 2012

The effects of a series of adenosine derivatives on morphine antinoceptive effect were investigated in rats by the ‘tail‐flick’ method.
2‐Chloroadenosine (CADO) and L‐N6‐phenylisopropyladenosine (L‐PIA), given intraperitoneally, caused decreased morphine antinociception.
Intracerebroventricular injections of CADO, L‐PIA and 5′‐N‐ethylcarboxamide adenosine (NECA), but not of 2′‐deoxyadenosine, antagonized morphine antinociception.
The effects of both central and peripheral injections of CADO and L‐PIA on morphine antinociception were partially reversed by caffeine.
Intracerebroventricular injection of dibutyryl‐cyclic 3′,5′ adenosine monophosphate (db cyclic AMP) had no effect on morphine antinociception.
These data indicate that adenosine plays a role in morphine‐induced antinociception. The results are discussed in terms of postulated effects of adenosine derivatives on adenylate cyclase.
Phentolamine‐induced rhythmic contractions in bladder detrusor muscle of guinea‐pig
Authors: Satake Nobuhiro , Shibata Shoji , Ueda Shoichi 
Published: July 2012

Phentolamine caused a rhythmic contraction concentration‐dependently without affecting resting tone in the detrusor muscle.
Prazosin, yohimbine, propranolol, noradrenaline, Clonidine or isoprenaline failed to cause the rhythmic contraction. These agents did not modify the response to phentolamine suggesting no involvement of α‐or β‐adrenoceptors in the response to phentolamine.
Chlorpheniramine, Cimetidine, methysergide, SK&F 83566, atropine, bretylium, hemicholinium or tetrodotoxin failed to inhibit the response to phentolamine. These results suggest that the effect of phentolamine is not mediated through histaminergic, 5‐hydroxytryptaminergic, dopaminergic or cholinergic systems, or through transmitter release from nerve endings.
Prostaglandin F2α (PGF2α), arachidonic acid but not ATP caused rhythmic contractions which resembled the response to phentolamine. Potassium also caused a contraction with increasing resting tone.
Following treatment with nifedipine, or incubation in a Ca2+‐ free medium, the responses to phentolamine, PGF2α, arachidonic acid and potassium were markedly inhibited or abolished.
Cyclo‐oxygenase inhibitors such as indomethacin, aspirin and corticosterone inhibited or abolished the responses to phentolamine and arachidonic acid but did not inhibit the response to PGF2α.
The results suggest that the phentolamine‐induced rhythmic contraction may, at least in part, result from the cyclo‐oxygenase metabolite of arachidonic acid in guinea‐pig detrusor muscles and a consequent increase in the transmembrane Ca2+‐influx.