bluuebunny/crossref_metadata_2025_split huggingface dataset:
5‐HT1‐like receptors requiring functional cyclo‐oxygenase and 5‐HT2 receptors independent of cyclo‐oxygenase mediate contraction of the human umbilical artery
Authors: MacLennan S.J. , Whittle M.J. , McGrath J.C. 
Published: July 2012

The interactions between 5‐hydroxytryptamine (5‐HT) and the antagonists ketanserin, methysergide and phentolamine were studied in isolated preparations of human umbilical artery (HUA) at physiological oxygen tension (Po2 ∽ 15 mmHg) and at high Po2 (∽ 120 mmHg).
At physiological Po2 ketanserin, methysergide and phentolamine behaved as silent competitive antagonists of the 5‐HT‐induced contraction of HUA. pA2 values calculated by Schild analysis were 8.92, 8.52 and 6.37, respectively.
At high Po2, 5‐HT‐induced contractions were antagonised in a biphasic manner by ketanserin (0.1 μm); the response to low but not to high concentrations of 5‐HT was resistant to blockade by ketanserin. The ketanserin‐resistant component was abolished following cyclo‐oxygenase inhibition by indomethacin (1 μm).
At high Po2, methysergide behaved as a partial agonist. Methysergide‐induced contractions were inhibited but not abolished by indomethacin, and resistant to 5‐HT2 receptor and α1‐adrenoceptor blockade.
At high Po2 the component of the response to 5‐HT mediated by the ketanserin‐resistant receptor was mimicked by the selective 5‐HT1‐like receptor agonist 5‐carboxamidotryptamine (5‐CT): 5‐CT was 7 fold more potent than 5‐HT.
At high Po2 the component of the response to 5‐HT mediated by the ketanserin‐resistant receptor was antagonised by phentolamine and the selective α2‐adrenoceptor antagonist Wy 26703.
These results suggest that (i) at physiological Po2 5‐HT2 receptors almost exclusively mediate contractions induced by 5‐HT, and (ii) at high Po2 the agonist potency order of 5‐CT > 5‐HT > methysergide suggests that ketanserin‐resistant responses are mediated by 5‐HT1‐like receptors which require functional cyclo‐oxygenase.
A purified lipocortin shares the anti‐inflammatory effect of glucocorticosteroids in vivo in mice
Authors: Errasfa Mourad , Russo‐Marie Françoise 
Published: July 2012

The injection of a suspension of a polyacrylamide gel (bio gel) into the dorsal subcutaneous area of mice induced an inflammatory reaction and the migration of neutrophils towards the inflamed site.
The intravenous administration of anti‐inflammatory drugs (dexamethasone, indomethacin and lysine‐acetylsalicylate) to Polyacrylamide gel‐treated mice inhibited the accumulation of neutrophils in the inflamed site.
A similar administration of a 36 K mouse lipocortin, induced a strong dose‐dependent inhibition of neutrophil accumulation in the inflamed site.
Dexamethasone and lipocortin inhibited the production of eicosanoids, prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in the inflamed site of Polyacrylamide gel‐treated mice.
Lipocortin impaired both phospholipase A2 (PLA2) activity and chemotaxis of isolated inflammatory neutrophils.
The present studies show an in vivo anti‐inflammatory effect of lipocortin similar to that of glucocorticosteroids. In agreement with recent data on the extracellular effects of various lipocortins, these results might implicate lipocortin(s) in the anti‐inflammatory effects of glucocorticosteroids.
Non classical, multiple‐site interaction of [3H]‐prazosin with the α1‐adrenoceptor of intact BC3H1 cells
Authors: Sladeczek Fritz , Kirk Christopher J. , Bockaert Joël , Schmidt Bernard H. 
Published: July 2012

In intact BC3H1 cells the EC50 of noradrenaline (NA) for the inositol phosphate response measured at 37°C (EC50 = 193 nm) was much lower than its apparent dissociation constant (Ki37°c = 83.211 μm) determined at this temperature by [3H]‐prazosin binding.
After pretreatment of the cells with NA at 37°C for 45 min, the time used in binding assays at this temperature, this difference between EC50 and Ki37°c did not decrease significantly. An agonist‐induced reduction in α1‐adrenoceptor affinity can therefore not explain the very high Ki37°C value.
NA pretreatment at 37°C decreased the number of [3H]‐prazosin binding sites (assessed by whole cell binding at 2°C) by only 49%; not by 100%, the value expected if agonist‐induced receptor internalization were the origin of the very low Ki37°C.
The EC50 of NA for the inositol phosphate response in the presence of 156 pM [3H]‐prazosin was 1.841 μm but the IC50 of NA for the inhibition of [3H]‐prazosin binding (126 pm) was 316 μm. As there is no α1‐adrenoceptor reserve in these cells we propose that at 37°C [3H]‐prazosin interacts, not only with the catecholamine recognition site (site 1) of the receptor, but also reacts weakly with another site from which it cannot be directly displaced by catecholamine‐like substances (site 2).
Nitric oxide synthesized from L‐arginine regulates vascular tone in the coronary circulation of the rabbit
Authors: Amezcua J.L. , Palmer R.M.J. , de Souza B.M. , Moncada S. 
Published: July 2012

The role of nitric oxide (NO) in the regulation of the vascular tone of the coronary circulation of the Langendorff‐perfused rabbit heart was investigated.
NG‐monomethyl‐L‐arginine (L‐NMMA; 10–100 μm), a specific inhibitor of NO formation from L‐arginine (L‐Arg), but not its D‐enantiomer (D‐NMMA; 100 μm) produced a dose‐related, sustained increase in the coronary perfusion pressure (CPP). In addition, L‐NMMA inhibited the vasodilator responses of acetylcholine (ACh), unmasking in some instances its direct vasoconstrictor effect. These effects of L‐NMMA were attenuated by L‐Arg.
L‐NMMA (10 and 30 μm), but not D‐NMMA (30 μm), caused a long‐lasting inhibition of NO formation which was reversed by L‐Arg (30 and 100 μm), but not by D‐Arg (100 μm).
This study indicates that the formation of NO from L‐Arg in the coronary circulation of the rabbit plays a role both as a regulator of vascular tone and as a mediator of the vasodilatation induced by ACh.
Characterization of adenosine receptors in guinea‐pig isolated left atria
Authors: Jahnel Ulrich , Nawrath Hermann 
Published: July 2012

The effects of purinergic stimulation on action potential, force of contraction, 86Rb efflux and 45Ca uptake were investigated in guinea‐pig left atria.
Adenosine exerted a negative inotropic effect which was antagonized by adenosine deaminase but enhanced by dipyridamole.
The negative inotropic effect of adenosine was mimicked by 5′‐(N‐ethyl)‐carboxamido‐adenosine (NECA) and the isomers of N6‐(phenyl‐isopropyl)‐adenosine, R‐PIA and S‐PIA. NECA and R‐PIA were about 1000 times more potent than adenosine, whereas R‐PIA was about 100 times more potent than S‐PIA.
The inotropic effects of adenosine (in the presence of dipyridamole), NECA, R‐PIA and S‐PIA were competitively antagonized either by theophylline (pA2 about 4.5) or 8‐phenyltheophylline (pA2 about 6.3).
NECA and R‐PIA shortened the action potential duration and increased the rate constant of the efflux of 86Rb in a concentration‐dependent manner with no differences in potency; the effects were competitively antagonized by 8‐phenyltheophylline.
Barium ions reduced the efflux of 86Rb under control conditions and antagonized the increase induced by NECA and R‐PIA.
NECA and R‐PIA significantly reduced 45Ca uptake in beating preparations.
It is concluded that adenosine, NECA and R‐PIA activate a common receptor population (P1 or A3) on the outside of the cell membrane of atrial heart muscle to increase the potassium conductance and to reduce the action potential and, thereby, calcium influx and force of contraction.
Effect of age and methacholine on the rate and coronary flow of isolated hearts of diabetic rats
Authors: Li Xiaojiang , Tanz Ralph D. , Chang K.S.K. 
Published: July 2012

Isolated hearts perfused by the method of Langendorff from 6, 12 and 24 week streptozotocin (STZ) diabetic rats displayed a significant bradycardia following 60 min equilibration. The rate of hearts from 12‐week diabetic rats (164 ± 17) displayed the greatest bradycardia compared to age‐matched controls (268 ± 15; P < 0.001), and diabetics treated with insulin (232 ± 17; P < 0.01), but by 52 weeks the heart rate of the 3 groups was similar. With advancing age the effect of STZ diabetes on the rate of rat isolated perfused hearts remained unchanged but the rate of the control and diabetic + insulin groups declined.
Hearts from 6–52 week STZ‐treated rats were found to be more sensitive to the negative chronotropic effect of methacholine, the greatest difference occurring in hearts from the 12 week animals. Atropine (10−7m) did not affect the resting heart rate of age‐matched controls or diabetics but blocked methacholine (2.6 × 10−6m)‐induced bradycardia in both, suggesting that the site of action of diabetic bradycardia is not the muscarinic receptors.
At the end of equilibration there was a significant decrease in coronary flow in hearts from 12 week diabetic animals. In spontaneously beating diabetic rat hearts administration of methacholine (2.6 × 10−6m) produced a significantly greater decrease in coronary flow in the 12, 24 and 52 week diabetic hearts. When electrically paced (5 Hz) however, there was no difference in response to methacholine between the three groups except at 52 weeks between the age‐matched control and diabetic groups. This suggests that the more pronounced reduction induced by methacholine on the coronary flow of diabetic hearts is secondary to its negative chronotropic effect.
In general, hearts from diabetic animals treated with insulin respond similarly to their age‐matched controls in the presence and absence of methacholine.
Actions of tachykinins on the rabbit mesenteric artery: substance P and [Glp6,L‐Pro9]SP6–11 are potent agonists for endothelial neurokinin‐1 receptors
Authors: Stewart‐Lee Anne , Burnstock Geoffrey 
Published: July 2012

Identification of the subtype of neurokinin receptor on the endothelium of the rabbit mesenteric artery was demonstrated by comparing the relative potencies of the naturally occurring tachykinins, substance P, neurokinin A and neurokinin B and the highly selective agonists [Glp6,L‐Pro9]SP6–11 (L‐Pro), [Glp6,D‐Pro9]SP6–11 (D‐Pro) and N‐succinyl‐[Asp6,MePhe8]SP6–11 (senktide).
Relaxations of the rabbit mesenteric artery to substance P, neurokinin A and neurokinin B were concentration‐dependent and were abolished by the removal of the endothelium.
Substance P was more potent than neurokinin A or neurokinin B and L‐Pro was more potent than D‐Pro or senktide.
Substance P, neurokinin A and neurokinin B all significantly reduced the nerve‐mediated contractile response in the presence of the endothelium at a concentration of 0.1 μm, with a rank order of potency substance P > neurokinin A > neurokinin B.
At a concentration of 0.1 μm, L‐Pro also significantly reduced the nerve‐mediated contractile response, unlike D‐Pro and senktide.
It is concluded that the relaxation of the rabbit mesenteric artery produced by substance P is mediated by neurokinin‐1 receptors (NK‐1) located on the endothelium. Furthermore, of the analogues, L‐Pro was particularly potent for these receptors.
Microelectrode study on the ionic mechanisms which contribute to the noradrenaline‐induced depolarization in isolated cells of the rabbit portal vein
Authors: Amédée T. , Large W.A. 
Published: July 2012

Experiments were carried out to determine the identity of the ionic mechanisms which contribute to the noradrenaline‐evoked depolarization recorded with microelectrodes in freshly dispersed rabbit portal vein cells.
In normal physiological salt solution with microelectrodes containing 1 m NaCl the reversal potential (Er) of the noradrenaline‐induced response was −7.6 ± 2.9 mV. When the external NaCl was replaced by equipmolar concentrations of NaI, NaBr and NaNO3, Er was −33 ± 3.5 mV, −29.1 ± 5.2 mV and −18.4 ± 1.1 mV, respectively.
In physiological salt solution Er of noradrenaline‐evoked responses recorded with electrodes filled with 1m NaI or 1m NaNO3 was + 16.3 + 3.9mV and +10.0 ± 7.6 mV, respectively. These results suggest that an increase in anion conductance contributes to the depolarization to noradrenaline.
Data from experiments with organic anions indicated that glutamate behaves as a less permeant anion but that benzenesulphonate blocks the anion conductance to unmask another conductance mechanism activated by noradrenaline.
When external NaCl was substituted by choline Cl and Tris Cl Er was −21.3 ± 3.7 mV and −20.5 ± 2.8 mV, respectively. These results suggest that noradrenaline also activates a cation conductance mechanism in freshly dispersed rabbit portal vein cells. It is concluded that the depolarization to noradrenaline recorded with a microelectrode is produced by the simultaneous activation of an anion channel and a separate cation channel.
Presence of T‐kininogen and kinins in sponge‐induced exudates in rats
Authors: Damas J. , Adam A. , Bourdon V. , Remade‐Volon G. 
Published: July 2012

The content of kinins and T‐kininogen (the third kininogen) in exudates induced by the subcutaneous implantation of saline‐soaked sponges have been measured by radioimmunoassay in normal Wistar rats and in Brown Norway rats from a strain which is deficient in high and low molecular weight kininogens.
In both strains, sponge implantation induced a rise of T‐kininogen in plasma with subsequent accumulation in the sponge exudate. This accumulation correlated with the extravasation of plasma proteins during the first 6 h. Bioassays showed that the T‐kinin moiety was retained in T‐kininogen.
In Wistar rats, a large release of immunoreactive kinins up to a mean value of 6.4 ng ml−1 was observed during the first 6 h and on the second day after the implantation. In Brown Norway rats, the kinin level in the exudates did not exceed 0.53 ng ml−1.
Of the kinins present during the first 6 h in the exudates withdrawn from Wistar rats, 60% were identified by high performance liquid chromatography as bradykinin.
The volume of the exudate induced by the implantation of dry sponges was smaller in Brown Norway rats than in Wistar rats.
We conclude that the role of T‐kininogen in this kind of exudate was mainly the inhibition of thiol proteinases and not the release of T‐kinin. In Wistar rats, bradykinin acts as a pro‐inflammatory factor during the first hours and may play a role during the healing process.
Lorazepam discontinuation promotes ‘inverse agonist’ effects of benzodiazepines
Authors: Schatzki Andrew , Lopez Fred , Greenblatt David J. , Shader Richard I. , Miller Lawrence G. 
Published: July 2012

The effects of lorazepam discontinuation on responses to benzodiazepine agonists and antagonists were studied in mice.
The convulsant dose of pentylenetetrazol was decreased after an acute dose of lorazepam (0.5 mg kg−1) at 4 days after drug discontinuation, compared to 1 or 7 days after discontinuation or to vehicle treatment.
The percentage of mice undergoing convulsions after an acute dose of FG 7142 (40 mg kg−1) was increased at 4 days after lorazapam discontinuation, compared to 1 or 7 days after discontinuation or to vehicle treatment.
After an acute dose (0.5 mg kg−1), lorazepam concentrations in cortex tended to be greater in lorazepam‐treated compared to vehicle‐treated mice at 4 days after discontinuation compared to 1 and 7 days.
These data indicate a shift toward reduced agonist sensitivity and increased inverse agonist sensitivity in mice 4 days after lorazepam discontinuation.
Inhibition of agonist‐stimulated inositol lipid metabolism by the anticonvulsant carbamazepine in rat hippocampus
Authors: McDermott Elaine E. , Logan S.D. 
Published: July 2012

The effect of the anticonvulsant, anti‐manic drug carbamazepine was examined on inositol lipid signalling in rat hippocampus in vitro.
Hippocampal miniprisms were labelled with [3H]‐inositol before stimulation with a variety of neuroactive agents that increase phosphoinositide turnover.
The presence of carbamazepine (0.1–100 μm) during labelling caused a dose‐related reduction of basal and carbachol‐evoked [3H]‐inositol phosphate accumulations. The effect of the drug on basal inositol phosphate levels was lost when slices were labelled with [3H]‐inositol before incubation with carbamazepine.
Incubation of slices with carbamazepine after labelling with [3H]‐inositol and before stimulation showed the inhibitory effect of the drug to be selective according to the agonist used. Responses to carbachol, histamine and the sodium‐channel agent veratrin were reduced by carbamazepine whilst the responses to 5‐hydroxytryptamine, noradrenaline and substance P were unaffected.
Inhibition of carbachol, histamine and veratrin‐induced stimulation by carbamazepine share a similar dependence on length of pre‐incubation time with the drug. However, the effect of carbamazepine (100 μm) on the respective dose‐response curves suggests that the mechanism of inhibition of the carbachol response differs from the inhibition of the histamine and veratrin responses. These effects may be significant in the mechanism of action of carbamazepine as an anticonvulsant and in its effectiveness against manic depression.
Multiple mechanisms in the motor responses of the guinea‐pig isolated urinary bladder to bradykinin
Authors: Maggi Carlo Alberto , Patacchini Riccardo , Santicioli Paolo , Geppetti Pierangelo , Cecconi Roberto , Giuliani Sandro , Meli Alberto 
Published: July 2012

Bradykinin (1 nM‐1 μm) produced a contraction of bladder strips excised from the dome of the guinea‐pig urinary bladder, an effect which was greatly enhanced by removal of the mucosal layer or by thiorphan (10 μm). All subsequent experiments were performed in mucosa‐free strips and in the presence of thiorphan.
In carbachol (5 μm)‐contracted strips, bradykinin produced a concentration (1 nM‐1 μm)‐dependent transient relaxation.
Kallidin was slightly more potent than bradykinin in producing a contraction and a relaxation of the carbachol‐induced tone. By contrast, [des‐Arg9]‐bradykinin, a selective B1 receptor agonist was barely effective up to 1 μm.
The contractile response to bradykinin was: (a) unaffected by either tetrodotoxin (1 μm), in vitro capsaicin desensitization (10 μm for 30 min) or apamin (0.1 μm); (b) antagonized by indomethacin (5 μm), the prostaglandin receptor antagonist SC‐19220 (100 μm) or the B2 receptor antagonist [D‐Arg0, Hyp3, Thi5,8, Phe7]‐bradykinin (10 μm) and (c) almost abolished by nifedipine (1 μm).
The antagonism of the contractile response to bradykinin produced by indomethacin and SC‐19220 was non‐additive while that produced by indomethacin and the B2 receptor antagonist was additive.
The relaxant response to bradykinin was unaffected by tetrodotoxin, in vitro capsaicin desensitization or indomethacin but antagonized in a competitive manner by the B2 receptor antagonist. Further, this response was abolished by apamin (0.1 μm) but unaffected by glibenclamide (1 μm).
Bradykinin (10 μm) produced a consistent release of calcitonin gene‐related peptide‐like immunoreactivity (CGRP‐LI) but not substance P‐LI from the guinea‐pig bladder muscle. CGRP‐LI release by bradykinin was greatly reduced in bladders exposed to indomethacin. [des‐Arg9]‐bradykinin (10 μm) was ineffective.
We conclude that: (a) bradykinin‐induced contraction involves activation of both B2 receptors and prostanoid synthesis, via distinct mechanisms which act by inducing calcium influx via nifedipine‐sensitive channels; (b) bradykinin‐induced relaxation involves activation of B2 receptors and opening of apamin‐sensitive potassium channels; (c) bradykinin stimulates sensory nerves in this tissue largely via prostanoid production.
Evidence for tonic activation of prejunctional β‐adrenoceptors in guinea‐pig pulmonary arteries by adrenaline derived from the adrenal medulla
Authors: Misu Yoshimi , Kuwahara Misako , Amano Hiro , Kubo Takao 
Published: July 2012

The effects of (+)‐carteolol 10−8 m to 10−6 m, a non‐selective β‐antagonist, applied cumulatively, on stimulation‐evoked 3H‐release at 1 Hz were studied in pulmonary arteries isolated from guinea‐pigs. The guinea‐pigs were subjected to either bilateral adrenalectomy, adrenalectomy followed by injections of deoxycorticosterone acetate (DOCA) and hydrocortisone, bilateral adrenodemedullation or a sham operation, and then loaded in vitro with [3H]‐noradrenaline.
Carteolol inhibited 3H‐output in arteries from sham‐operated animals in a concentration‐dependent manner. This inhibitory effect was not found in pulmonary arteries from animals subjected to adrenalectomy or adrenodemedullation. However, DOCA and hydrocortisone pretreatment, did not prevent the disappearance of the carteolol‐induced inhibition of 3H‐release.
Adrenalectomy and adrenodemedullation depleted or markedly reduced the endogenous contents of adrenaline in pulmonary arteries without altering the levels of dopamine and noradrenaline.
It is concluded that adrenaline, mainly derived from the adrenal medulla, acts as an endogenous agonist for tonically functioning prejunctional β‐adrenoceptors in guinea‐pig pulmonary arteries, probably by being taken up and co‐released with noradrenaline.
Alveolar macrophages and eicosanoids but not neutrophils, mediate bronchoconstriction induced by FMLP in the guinea‐pig
Authors: Boukili M. Abdelhakim , Bureau Michel‐Francis , Lellouch‐Tubiana Arielle , Lefort Jean , Simon Marie‐Thérèse , Vargaftig B. Boris 
Published: July 2012

N‐formyl‐methionyl‐leucyl‐phenylalanine (FMLP), when administered by aerosol to guinea‐pigs, induced a dose‐dependent bronchoconstriction (BC) with no overt effect on platelet and leukocyte blood counts. Repeated administration of FMLP by aerosol was followed by desensitization.
Electron microscopy studies showed that administration of FMLP by aerosol is accompanied by alveolar macrophage activation, accumulation and aggregation in the alveolar lumens. Non‐degranulated eosinophils were observed in the lungs and a few platelet micro‐aggregates in the pulmonary microvasculature.
No significant accumulation of 131I‐labelled albumin, 111In‐labelled neutrophils or 111In‐labelled platelets was detected in the lungs after the administration of FMLP by aerosol, whereas the intravenous administration was accompanied by an increase of extravascular albumin and significant neutrophil sequestration in the lungs.
Aspirin administered intravenously or by aerosol reduced significantly the BC induced by an aerosol of FMLP. By contrast, intravenous indomethacin reduced only BC induced by the sub‐maximal dose of FMLP as an aerosol whereas, when administered by inhalation, it inhibited BC induced by FMLP administered either intravenously or by aerosol at all the concentrations tested.
FMLP induced a dose‐dependent contraction of the guinea‐pig trachea, which was not inhibited by indomethacin.
The dual cyclo‐oxygenase/lipoxygenase inhibitor compound BW755C suppressed the BC induced by an aerosol of FMLP at all the concentrations used, whereas the histamine H1‐antagonist mepyramine was inactive.
Leukocyte depletion with vinblastine failed to reduce BC induced by intravenous or an aerosol of FMLP.
Our studies indicate that: (a) FMLP administered by aerosol induces dose‐dependent BC followed by desensitization, indicating that local mechanisms account for BC; (b) BC induced by i.v. FMLP, but not by its inhalation, is accompanied by albumin extravasation and neutrophil sequestration in the lungs; (c) BC by either i.v. or an aerosol of FMLP is not due to neutrophil activation; (d) inhalation of FMLP induces BC accompanied by accumulation of activated alveolar macrophages, non‐degranulated eosinophils and a few platelet microaggregates in the lung; (e) both cyclo‐oxygenase and lipoxygenase metabolites are involved in the BC induced by an aerosol of FMLP.