bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential effects of Na+,K+‐ATPase inhibition by ouabain on acid secretory responses to histamine and bethanechol in the mouse isolated stomach
Authors: Horie Syunji , Yano Shingo , Watanabe Kazuo 
Published: July 2012

The effect of Na+,K+‐ATPase inhibition by ouabain on gastric acid secretion was studied in the mouse isolated whole stomach preparation.
Ouabain caused a transient enhancement of histamine‐induced gastric acid secretion followed by an inhibitory phase. On the other hand, ouabain caused a rapid reduction of bethanechol‐stimulated acid secretion without an enhancement phase.
In dibutyryl cyclic AMP‐induced acid secretion, ouabain led to a transient increase in acid secretion followed by a fall, as was seen with the histamine stimulation. Ouabain caused a rapid reduction of A23187‐induced acid secretion.
Ouabain by itself increased basal acid secretion, and thereafter slowly suppressed the acid secretion.
Atropine inhibited both the ouabain‐induced enhancement of the stimulated gastric acid secretion and the ouabain‐induced stimulation of basal acid secretion.
The present study showed that Na+,K+‐ATPase inhibition by ouabain caused a phasic enhancement of the stimulated gastric acid secretion through release of endogenous acetylcholine when the secretagogues act via an intracellular cyclic AMP pathway. It also inhibited the stimulated acid secretion irrespective of secretagogues, probably through its inhibitory effect on Na+,K+‐ATPase in the gastric parietal cell.
Presence of P2‐purinoceptors in the rat pineal gland
Authors: Ferreira Zulma S. , Cipolla‐Neto J. , Markus Regina P. 
Published: July 2012

The effects of noradrenaline, ATP, adenylyl‐imidodiphosphate (AMP‐PNP), adenosine, α,β‐methylene‐ATP and the P2‐purinoceptor antagonist, suramin on N′‐acetyl‐5‐hydroxytryptamine production were studied in cultured denervated rat pineal glands.
Noradrenaline (3 nm – 1 μm) increased N′‐acetyl‐5‐hydroxytryptamine production as measured both in the gland and the culture medium.
In noradrenaline (10 nm)‐stimulated pineal glands, ATP (0.03 nm – 1 mm) or AMP‐PNP (0.1 μm – 1 mm) increased N′‐acetyl‐5‐hydroxytryptamine production in a concentration‐dependent manner.
α,β‐Methylene‐ATP at the concentration of 0.1 mm, but not 3 μm, attenuated the enhancement by ATP (0.1 mm) of noradrenaline (10 nm)‐induced N′‐acetyl‐5‐hydroxytryptamine production.
Suramin (0.1 mm) blocked the potentiating effect of ATP (0.1 mm), but not the potentiating effect of adenosine (0.1 mm) in glands incubated with noradrenaline (10 nm).
These findings suggest that the rat pineal gland possesses P2‐purinoceptors which when stimulated potentiate the effect of noradrenaline but do not, by themselves, induce an increase in N′‐acetyl‐5‐hydroxytryptamine production.
Drug modulation of antigen‐induced paw oedema in guinea‐pigs: effects of lipopolysaccharide, tumour necrosis factor and leucocyte depletion
Authors: da Motta Joelson I. Braga , Cunha Fernando Q. , Vargaftig Bernardo Boris , Ferreira Sergio H. 
Published: July 2012

In guinea‐pigs previously sensitized with ovalbumin, the intra‐plantar administration of the antigen induced dose‐dependent and sustained oedema. An intense infiltrate of neutrophils and eosinophils was observed at the peak of the oedema (4 h).
Oedema induced by ovalbumin at the doses of 50 or 200 μg/paw was not inhibited by antihistamines (meclizine and cetirizine), a PAF antagonist (BN 50730), a cyclo‐oxygenase inhibitor (indomethacin), a lipoxygenase inhibitor (MK‐886), a dual type lipo‐ and cyclo‐oxygenase inhibitor (NDGA), a bradykinin antagonist (Hoe 140) or the combination of cetirizine, MK‐886, indomethacin and BN 50730. These drugs did inhibit paw oedema induced by their specific agonists or by carrageenin. These results suggest that histamine, PAF, prostaglandins, leukotrienes or bradykinin are not important in the development of immune paw oedema in guinea‐pigs.
Dexamethasone (10 mg kg−1) inhibited oedema induced by ovalbumin (50 or 200 μg/paw, P < 0.05). This effect apparently does not result from inhibition of arachidonate metabolism, since indomethacin, MK‐886 and NDGA were without effect.
Oedema induced by ovalbumin (50 or 200 μg/paw) was also inhibited by azelastine. This effect was not due to the anti‐histaminic property of azelastine since two other potent‐antihistamines, meclizine and cetirizine, were ineffective.
Intravenous injection of lipopolysaccharide (LPS) dose‐dependently inhibited the oedema induced by ovalbumin (200 μg/paw). This effect could not be attributed to hypotension or leucopenia since the maximal dose applied (81 μg kg−1) did not induce significant changes in the blood pressure or in the white blood cell levels of the animals. It is suggested that the effect of LPS is mediated by the endogenous release of cytokines, including tumour necrosis factor (TNFα). Murine TNFα dose‐dependently (9–81 μg kg−1) inhibited the paw oedema induced by ovalbumin.
The anti‐oedematogenic effects of LPS and/or TNFα are possibly associated with their capacity to inhibit leucocyte emigration. Accordingly, guinea‐pigs rendered leucopenic with vinblastine exhibited less intense oedema after ovalbumin. Vinblastine did not affect oedema induced by PAF or bradykinin, indicating that vascular responsiveness was not involved.
Subtypes of purinoceptors in rat and dog urinary bladder smooth muscles
Authors: Suzuki Hideka , Kokubun Shinichiro 
Published: July 2012

Both adenosine and adenosine 5′‐triphosphate (ATP) (10 μm and 100 μm) relaxed 10 μm acetylcholine (ACh)‐induced contraction of rat bladder strips, which was completely antagonized by 100 μm 8‐(p‐sulphophenyl) theophylline. In dog bladder neither adenosine nor ATP inhibited ACh‐induced contraction.
P2x‐purinoceptor agonists contracted both rat and dog bladder strips with the potency order of α,β‐MeATP > ATP > ADP.
α,β‐MeADP (100 μm) induced a contraction of the rat bladder strip even after desensitization of P2x‐purinoceptors but failed to contract the dog bladder strip.
2‐MeSATP (1 μm to 300 μm) concentration‐dependently induced contraction of rat bladder strips; this contraction was significantly inhibited after desensitization of P2x‐purinoceptors. Cibacron blue 3GA (100 μm) antagonized the drug at concentrations lower than 30 μm, whereas it augmented the response to the drug at concentrations above 30 μm.
ADPβS (1 μm to 1 mm) concentration‐dependently induced contraction of rat bladder strips after desensitization of P2x‐purinoceptors; a contraction which was significantly antagonized by cibacron blue 3GA (100 μm).
It is concluded that three subtypes of purinoceptors, P1 (mediating relaxation), and P2x and another type of P2 (mediating contraction), exist in rat urinary bladder smooth muscle, whereas a single subtype of the receptor, P2x‐purinoceptor (mediating contraction) occurs in dog urinary bladder smooth muscle.
Cardiovascular and behavioural effects of centrally administered neuropeptide K in the rat: receptor characterization
Authors: Prat Alexandre , Picard Pierre , Couture Réjean 
Published: July 2012

The cardiovascular and behavioural responses to intracerebroventricularly (i.c.v.) administered neuropeptide K (NPK) were studied in conscious rats. The central effects of NPK were characterized by pretreatment (i.c.v.) with selective antagonists for the NK1 ((±)‐CP 96345 and RP 67580), NK2 (SR 48968) and NK3 (R 487) receptors.
NPK (10–65 pmol) induced tachycardia and dose‐dependent increases of mean arterial blood pressure. The cardiovascular responses reached a maximum within 3 min post‐injection and lasted for more than 1 h. Concurrently, NPK produced dose‐dependent increases of face washing, head scratching, grooming, walking and wet dog shakes.
A desensitization of most of the behavioural responses (except head scratching) but not of the cardiovascular response was shown when two consecutive injections of 25 pmol NPK were given 24 h apart.
Both the cardiovascular and behavioural responses (except the head scratching) to 25 pmol NPK were blocked by pre‐administration (i.c.v.) of 6.5 nmol (±)‐CP 96345 or RP 67580 given 5 min earlier. No inhibition of NPK responses was observed when 6.5 nmol SR 48968 or R 487 were used in a similar study. Additionally, NPK effects were significantly reduced 24 h after the prior injection of (±)‐CP 96345 but not of RP 67580.
These results support the involvement of NK1 receptors in the cardiovascular and behavioural effects of i.c.v. NPK. Thus, this peptide may play a putative role in central cardiovascular regulation as it is the most potent endogenous tachykinin described centrally, to date.
Differential effects of lumenal l‐arginine and NG‐nitro l‐arginine on blood flow and water fluxes in rat ileum
Authors: Mailman David 
Published: July 2012

The role of endogenous mucosal nitric oxide (NO) in the local regulation of H2O absorption and blood flow in rat ileum was studied by perfusing l‐arginine (l‐Arg) (0.1–1.0 mm) and NG‐nitro l‐arginine (l‐NOARG) (0.01–1.0 mm) through the lumen. d‐Arginine (d‐Arg) or l‐Arg (1 mm), combined with l‐NOARG, were used to determine if any of the measured intestinal effects of l‐NOARG were exerted through NO formation.
Net and unidirectional H2O fluxes and effective mucosal blood flow were measured using 3H2O and [14C]‐inulin in the perfusate. Mucosal NO formation was measured as the appearance of lumenal NO2−.
l‐NOARG, beginning at a concentration of 0.1 mm, decreased net H2O absorption, but had only minor effects on unidirectional H2O fluxes or on blood flow. l‐NOARG increased blood pressure, beginning at a concentration of 0.5 mm.
l‐Arg had no significant effects on net H2O absorption or blood pressure, and only minor effects on unidirectional H2O fluxes and blood flow.
NO appearance in the lumen was marginally decreased by 1.0 mm l‐NOARG, but not increased by l‐Arg.
Mucosal blood flow resistance paralleled systemic blood pressure suggesting that vascular effects on the mucosa were exerted only after l‐NOARG had reached the general circulation.
Lumenal l‐Arg reversed the effects of lumenal l‐NOARG on net H2O absorption and blood pressure, but d‐Arg did not.
It was concluded that there is tonic NO production by the rat intestinal mucosa that promotes H2O absorption, but does not affect blood flow resistance. Mucosal NO production was not related to the observed effects on mucosal function.
Lithium‐induced decrease in spontaneous Ca2+ oscillations in single GH3 rat pituitary cells
Authors: Varney Mark A. , Galione Antony , Watson Steve P. 
Published: July 2012

Measurement of [Ca2+]i in single rat pituitary GH3 cells by dynamic single cell imaging techniques demonstrated that under basal conditions there is a large variation in the temporal pattern of [Ca2+]i signalling between individual cells ranging from high frequency asynchronous oscillations to quiescence.
We have reported previously that treatment of GH3 cells with 1 mm Li+ (a concentration used therapeutically in the treatment of manic depression) for 7 days reduces basal and thyrotrophin‐releasing hormone (TRH)‐stimulated levels of mass inositol 1,4,5‐trisphosphate [Ins(1,4,5)P3]. In the present study, we show that this is associated with a reduction in the number of cells exhibiting basal Ca2+ oscillations over a sampling period of 60 s, whereas the maximum amplitude of oscillations is unaffected.
The pattern of [Ca2+]i responses to the agonist TRH varied considerably between individual cells, making quantitation of the responses difficult; however, data obtained from measurements made on a population of cells showed that increases in peak [Ca2+]i induced by high concentrations of TRH were reduced in cells treated with 1 mm Li+ for 7 days relative to control cells.
The sensitivity of the phosphoinositide pathway to [Ca2+]i was investigated by loading GH3 cells with BAPTA/AM at a concentration sufficient to lower ‘basal’ [Ca2+]i in a population of cells and to inhibit agonist‐stimulated increases in [Ca2+]i. Under these conditions, basal and TRH‐stimulated mass Ins(1,4,5)P3 levels were unaffected.
These results demonstrate that a 7‐day Li+ treatment leads to an alteration in Ca2+ signalling, in particular by reducing the number of cells exhibiting high frequency Ca2+ oscillations under basal conditions. The significance of these results to the clinical effectiveness of Li+ in the treatment of manic depression is discussed.
Noradrenergic‐nitrergic interactions in the rat anococcygeus muscle: evidence for postjunctional modulation by nitric oxide
Authors: Kasakov Lübomir , Belai Abebech , Vlaskovska Mila , Burnstock Geoffrey 
Published: July 2012

The distribution of NADPH‐diaphorase positive and catecholamine‐containing nerve structures, and functional noradrenergic‐nitrergic interactions, were studied in the rat anococcygeus muscle.
The morphological findings demonstrated NADPH‐diaphorase positive neurones mostly as aggregates in intramural ganglia, nerve tracts and few single nerve fibres forming plexus‐like structures.
The nitric oxide synthase inhibitor NG‐nitro‐l‐arginine (l‐NOARG) inhibited concentration‐dependently the nitrergic relaxation, an effect reversed by l‐arginine. The drug had dual effects on noradrenergic contractile responses: at lower concentrations (0.1–10 μm) it decreased the amplitude of contractions and this was not affected by l‐arginine; higher concentrations (50–500 μm) potentiated the contractions, an effect that was prevented by l‐arginine.
The electron acceptor, nitro blue tetrazolium (NBT) produced a rapid inhibition of the noradrenergic contractile responses (EC50 0.178 ± 0.041 μm). The drug decreased the tone of the preparations. However, it potentiated concentration‐dependently the nitrergic relaxations.
NBT (1 μm) had no significant effect on the relaxations induced by exogenously applied nitric oxide (NO)‐donor sodium nitroprusside (SNP, 0.01–50 μm). However, the effect of NBT (0.1–10 μm) on the electrically induced relaxation was significantly decreased by l‐NOARG (10 and 50 μm). The inhibition was of a non‐competitive type.
Neither l‐NOARG (100 μm) nor NBT (1 μm) had any effect on the spontaneous or electrically‐induced release of 3H‐radioactivity from the tissues preincubated in [3H]‐noradrenaline.
It is concluded that l‐arginine‐NO pathway can modulate noradrenergic transmission in the rat anococcygeus muscle at postjunctional, but not prejunctional site(s).
Mechanisms of sympathetic enhancement and inhibition of parasympathetically induced salivary secretion in anaesthetized dogs
Authors: Lung Mary A. 
Published: July 2012

The effects of superimposed and continuous sympathetic nerve stimulation on submandibular parasympathetic salivation were investigated in anaesthetized dogs.
Superimposed sympathetic nerve stimulation (1–2 min) initially enhanced and later inhibited salivary secretion induced by parasympathetic nerve stimulation (2–8 Hz) in glands with uncontrolled blood supply or constant‐flow vascular perfusion. Propranolol (0.05 mg kg−1, i.a.) did not affect the diphasic sympathetic action whereas phentolamine (0.1 mg kg−1, i.a.) abolished it. Prazosin (0.025 mg kg−1, i.a.) greatly lessened the initial enhancement while yohimbine (0.025 mg kg−1, i.a.) alleviated the late inhibition.
Salivary secretion, induced by parasympathetic nerve stimulation (4 Hz) or acetylcholine infusion (10 μg kg−1 min−1, i.a.), was abolished by atropine (0.05 mg kg−1, i.a.), increased by phenylephrine infusion (0.25 μg kg−1 min−1, i.a.) and depressed by clonidine infusion (0.75 μg kg−1 min−1, i.a.). Hexamethionium (12.5 mg kg−1, i.a.) abolished the nerve‐induced secretion but had no effect on the acetylcholine‐induced secretion.
Continuous background sympathetic nerve stimulation decreased parasympathetic nerve‐induced salivary secretion in glands with uncontrolled blood supply or constant‐flow vascular perfusion.
These results show that parasympathetic salivation can be modified by the sympathetic system at the postsynaptic level;
AT1 receptor characteristics of angiotensin analogue binding in human synovium
Authors: Walsh David A. , Suzuki Takahiro , Knock Gregory A. , Blake David R. , Polak Julia M. , Wharton John 
Published: July 2012

Angiotensin II (AII) reduces blood flow, modulates vascular remodelling and is a growth factor. Human inflammatory arthritides are characterized by synovial hypoperfusion, hypoxia and proliferation. We aimed to localize and characterize receptors for AII in human synovium.
We used quantitative in vitro receptor autoradiography with [125I]‐(Sar1, Ile8)AII and [125I]‐AII on human synovium from patients with chondromalacia patellae, osteoarthritis and rheumatoid arthritis.
[125I]‐(Sar1, Ile8)AII and [125I]‐AII bound to similar sites on synovial blood vessels, lining cells and stroma. Binding to microvessels (< 100 μm diameter) was more dense than to arteriolar media, and vascular binding was more dense than that to lining cells and stroma.
Microvessels and arterioles which displayed angiotensin converting enzyme‐like immunoreactivity also displayed specific binding of [125I]‐(Sar1, Ile8)AII.
Specific binding of [125I]‐(Sar1, Ile8)AII to each structure was completely inhibited by 10 μm dithiothreitol and was inhibited by unlabelled ligands with the rank order of potency (Sar1, Ile8)AII > AII > losartan = SKF108566 > PD123319 indicating an AT1 subclass of angiotensin receptor.
GTPγS (1 μm) abolished specific binding of [125I]‐AII and abolished the high affinity component of the binding inhibition curve for AII against [125I]‐(Sar1, Ile8)AII, indicating G protein coupling.
The distribution of [125I]‐(Sar1, Ile8)AII binding sites was similar in all disease groups and no significant differences in binding densities, affinities or specificities were observed between disease groups.
Locally generated AII may act on synovial AT1 receptors to modulate synovial perfusion and growth. Specific AT1 receptor antagonists should help elucidate the role of angiotensins in human arthritis.
Requirement for endothelium‐derived nitric oxide in vasodilatation produced by stimulation of cholinergic nerves in rat hindquarters
Authors: Loke K.E. , Sobey C.G. , Dusting G.J. , Woodman O.L. 
Published: July 2012

We aimed to determine whether nitric oxide (NO) and/or the endothelium is involved in cholinergic neurogenic vasodilatation in the rat isolated hindquarters.
The abdominal aorta was cannulated for perfusion of the rat hindquarters with Krebs bicarbonate solution containing phenylephrine, to induce basal constrictor tone. In the presence of noradrenergic neurone blockade with guanethidine (200 mg kg−1, i.p.) electrical stimulation of peri‐aortic nerves induced frequency‐dependent decreases in hindquarters perfusion pressure, indicating vasodilatation. Both the endothelium‐dependent vasodilator, acetylcholine (ACh) and the endothelium‐independent vasodilator, sodium nitroprusside (SNP) induced dose‐dependent decreases in perfusion pressure. In each experiment, responses to either nerve stimulation, ACh or SNP were recorded before and after treatment with saline vehicle, atropine (1 μm), NG‐nitro‐l‐arginine (l‐NOARG, 100 μm), l‐arginine (1 mm), l‐arginine plus l‐NOARG, or 3–3 cholamidopropyl dimethylammonio 1‐propanesulphonate (CHAPS, 30 mg). Hindquarters dilatation after each treatment was expressed as a percentage of the control response.
Following treatment with saline, responses to nerve stimulation and ACh were 99 ± 9% and 107 ± 10% of control, respectively demonstrating the reproducibility of these responses. Nerve stimulation‐induced dilatation was abolished by atropine (0 ± 0% of control, P < 0.05) or reduced to 14 ± 10% of control by NO synthase inhibition with l‐NOARG (P < 0.05). Dilator responses to ACh were also abolished by atropine (0 ± 0% of control, P < 0.05) or inhibited by l‐NOARG (59 ± 10% of control, P < 0.05), indicating that the neurogenic dilatation is cholinergic and is mediated by NO. The administration of the NO precursor, l‐arginine, prevented the inhibitory effect of l‐NOARG on dilator responses to nerve stimulation and ACh (l‐arginine plus l‐NOARG: 89 ± 13% and 122 ± 24% of control, respectively). In addition CHAPS, which removes endothelial cells, inhibited responses to both nerve stimulation (0 ± 0% of control, P < 0.05) and ACh (33 ± 8% of control, P<0.05). In contrast, no treatment significantly reduced the vasodilator responses to SNP.
These observations suggest that cholinergic neurogenic vasodilatation in the rat isolated hindquarters requires the synthesis and release of NO from the endothelium.
Effects of glibenclamide on systemic and splanchnic haemodynamics in conscious rats
Authors: Moreau Richard , Komeichi Hirokazu , Kirstetter Philippe , Yang Song , Aupetit‐Faisant Brigitte , Cailmail Stéphane , Lebrec Didier 
Published: July 2012

The effects of the sulphonylurea, glibenclamide (20 mg kg−1, i.v.), at a dose that blocks vascular potassium channels, on systemic and splanchnic haemodynamics (radioactive microspheres) were studied in conscious rats.
Glibenclamide significantly decreased cardiac index and hepatic artery blood flow while it significantly increased vascular resistance in systemic, portal and hepatic arterial territories.
In rats with suppressed cardiovascular reflexes, glibenclamide induced vasoconstriction in systemic, portal and hepatic arterial territories.
Intracerebroventricular administration of glibenclamide did not alter systemic or regional vascular tone.
Glibenclamide blunted the vasodilator effect of the potassium channel opener, diazoxide but not that of the L‐type calcium channel blocker, nicardipine.
Another sulphonylurea, glipizide (20 mg kg−1, i.v.), induced significant systemic and splanchnic vasoconstriction.
Thus, the glibenclamide‐induced blockade of vascular potassium channels caused a vasoconstriction in the systemic and splanchnic vascular beds. In these territories, therefore, the opening of glibenclamide‐sensitive potassium channels might be responsible for a basal vasodilator tone.
Blockade by 4,4′‐diisothiocyanatostilbene‐2,2′‐disulphonate (DIDS) of P2X‐purinoceptors in rat vas deferens
Authors: Bültmann Ralph , Starke Klaus 
Published: July 2012

The possibility of an antagonist effect of 4,4′‐diisothiocyanatostilbene‐2,2′‐disulphonate (DIDS) at P2X‐purinoceptors was studied in rat vas deferens.
DIDS reduced contractions elicited by α,β‐methylene ATP 3 μm, IC50 1.6 μm, but did not change contractions elicited by K+ 35 mm. DIDS 3.2 μm slightly shifted the concentration‐response curve of α,β‐methylene ATP to the right and reduced the maximum. DIDS 10 μm markedly decreased and DIDS 32 μm abolished contractions over the entire range of the α,β‐methylene ATP concentration‐response curve. DIDS 32 μm also abolished contractions elicited by ATP but did not change contractions elicited by noradrenaline. The antagonist effect of DIDS was only slowly reversible.
The presence of either suramin 320 μm or α,β‐methylene ATP 10 μm during the exposure to DIDS protected the tissue from the long‐lasting blocking effect of DIDS.
4,4′‐Diisothiocyanatodihydrostilbene‐2,2′‐disulphonate (H2DIDS) was equipotent with DIDS whereas several analogues in which one or both of the isothiocyanate residues were replaced were less effective or without effect against α,β‐methylene ATP.
DIDS attenuated the purinergic component of neurogenic contractions elicited by electrical field stimulation, IC50 3.9 μm, but did not change the adrenergic component.
It is concluded that DIDS causes a selective, long‐lasting, non‐equilibrium blockade of P2X‐purinoceptors in rat vas deferens. Due to this effect it also selectively blocks the purinergic component of neurogenic contractions.