bluuebunny/crossref_metadata_2025_split huggingface dataset:
The actions of neuropeptide Y and peptide YY on the hepatic arterial and portal vascular beds of the anaesthetized dog
Authors: Corder R. , Withrington P.G. 
Published: July 2012

The vascular actions of the two peptides, neuropeptide Y (NPY) and peptide YY (PYY) were compared with the transmitter noradrenaline (NA) on the arterial and portal vascular beds of the in situ liver of the anaesthetized dog.
The sole vascular response of the hepatic arterial vasculature to intra‐arterial administration of either NPY or PYY was vasoconstriction; the duration of these responses was longer than that to NA.
The maximum hepatic arterial vasoconstrictor responses to PYY and to NPY were significantly different and they were both significantly less than the maximum to NA (P > 0.001).
In contrast to its activity on the splenic arterial vasculature PYY was not more potent, on a molar basis, than NPY as an hepatic arterial vasoconstrictor agent. However, both peptides were significantly more potent than NA (P > 0.005).
Neither peptide, when injected intraportally, caused any change in intrahepatic portal inflow resistance.
Both peptides when administered intraportally in doses which were free of systemic effects caused hepatic arterial vasoconstriction.
Altered function of pulmonary endothelium following monocrotaline‐induced lung vascular injury in rats
Authors: Ito Katsuaki , Nakashima Teruyuki , Murakami Kazuyasu , Murakami Takayuki 
Published: July 2012

Based on the findings in the preceding paper we investigated the ability of pulmonary endothelial cells to metabolize prostaglandin F2α (PGF2α) and angiotensin I (AI), and to produce endothelium‐derived relaxing factor (EDRF) following lung vascular injury induced by monocrotaline in rats. The isometric tension of pulmonary artery rings isolated from rats 3–5 weeks after an injection of monocrotaline or saline was measured. For comparison the responses to drugs of the artery denuded of endothelium by rubbing were tested.
Acetylcholine‐induced relaxation of the rings precontracted by noradrenaline was diminished in the artery from moncrotaline‐treated rats, depending on the duration after treatment. The diminution was comparable to that in the control artery denuded of endothelium.
The contractile response to PGF2α was significantly augmented in the artery injured by monocrotaline. The similar augmentation was observed after the mechanical removal of endothelium in the control artery. Decrease of EDRF was not involved in the enhancement of contractile response to PGF2α in the monocrotaline‐injured artery.
AI caused a contraction, which was sensitive to captopril, in control rings, and also in moncrotaline‐injured rings to a similar degree. Removal of endothelium from the control artery did not modify the response to AI or to AII.
These results suggest that the monocrotaline treatment of rats suppresses the ability of pulmonary endothelium to produce EDRF and to degrade prostaglandins. The relative resistance of the AI response to endothelial injury suggests that the existence of converting enzyme is not restricted to the endothelium.
Pharmacological analysis of the effects of Bay K 8644 and organic calcium antagonists on the mouse isolated distal colon
Authors: Fontaine Jeanine , Lebrun Philippe 
Published: July 2012

Bay K 8644 (10−8 to 10−6 m) induced concentration‐related contractions of the longitudinal muscle of the mouse distal colon. The maximal responses were enhanced and the EC50 was lowered in the presence of tetrodotoxin (TTX; 1.5 × 10−7 m). The responses were not affected by atropine (10−7 m), mepyramine (2.5 × 10−7 m), methysergide (5 × 10−7 m), propranolol (10−6 m), phentolamine (10−6 m) or naloxone (4 × 10−7 m). By contrast, the contractile responses were inhibited by Ca2+ entry blockers (verapamil, nifedipine) and abolished in Ca2+‐free EGTA solution. These observations indicate that the contractile effects of Bay K 8644 are dependent on its ability to promote Ca2+ influx.
At 10−4 m, Bay K 8644 provoked a slow relaxation of the preparation. Moreover, from 10−5 m, Bay K 8644 markedly reduced the contractile responses to ACh and K+ depolarization. These inhibitory effects were comparable with those produced by nifedipine. Such data suggest that, at high concentrations, Bay K 8644 could act in part as a dihydropyridine Ca2+ channel antagonist.
Bay K 8644 (10−9 m) preferentially enhanced, while nifedipine (10−10 to 10−8 m) as well as verapamil (3 × 10−9 to 10−6 m) preferentially inhibited, the tonic component of the contractile response evoked by K+ depolarizing solution. This may indicate that different populations of voltage‐sensitive Ca2+ channels are involved in the biphasic response to K+ depolarization.
The biphasic contractile activity induced by ACh was barely enhanced by Bay K 8644 (10−9 m) and was less sensitive to Ca2+ entry blockers than the responses to KCl. These findings are discussed in terms of receptor‐operated channels and mobilization of bound calcium.
Inhibitory actions of amoxapine, a tricyclic antidepressant agent, on electrophysiological properties of mammalian isolated cardiac preparations
Authors: Kinugawa Toru , Kotake Hiroshi , Mashiba Hiroto 
Published: July 2012

The electrophysiological effects of amoxapine were examined in guinea‐pig isolated papillary muscles and rabbit sinoatrial nodes using a conventional microelectrode technique.
In papillary muscles, amoxapine above 10 μm caused a dose‐dependent decrease in the maximum upstroke velocity () of the action potential and in the action potential amplitude (APA), whereas the action potential duration at 90% repolarization (APD90) was significantly prolonged. For a decrease in , amoxapine produced a negative shift of the curve relating to the resting potential (Em) along the voltage axis to more negative membrane potentials.
Amoxapine also decreased and the overshoot potential of K+‐depolarized slow action potentials of papillary muscle preparations.
In spontaneously beating sinoatrial node preparations, amoxapine above 3 μm reduced the heart rate, , APA and the slope of phase 4 depolarization in a dose‐dependent manner.
It was concluded that amoxapine exerts inhibitory actions on fast‐ and slow‐ response fibres of the heart and these actions can be mainly explained by inhibition of both fast Na+ and slow Ca2+ channels.
Interactions of calcium antagonists and the calcium channel agonist Bay K 8644 on neurotransmission of the mouse isolated vas deferens
Authors: Rae Giles A. , Calixto João B. 
Published: July 2012

The present study compares the effects of verapamil and Bay K 8644 on twitches of the mouse vas deferens induced by field stimulation at 0.1 Hz. The influence of interactions between these drugs and nifedipine on neurotransmission was also investigated.
Bay K 8644 (0.1 nm‐3 μm) and verapamil (1–100 μm) potentiated twitches maximally by about 1000% (EC50 17.3 nm) and 300% (EC50 17.5 μm), respectively. Nifedipine (0.1 nM‐1μm) only reduced twitch magnitude (IC50 7.7 nm). All effects were reversed following washout.
Yohimbine (1–100 μm) reversed twitch potentiation caused by verapamil but not by Bay K 8644. Prazosin (1 μm) did not reduce basal twitch tension nor antagonize twitch potentiation by verapamil.
Twitch inhibition by nifedipine was unaltered by previous incubation with verapamil (30 μm), but Bay K 8644 (1 μm) shifted the curve to nifedipine 120 fold to the right. Previous incubation with nifedipine (1 μm) blocked potentiation induced by verapamil but did not modify responsiveness to Bay K 8644.
Previous addition of verapamil (30 μm) markedly enhanced twitch potentiation caused by Bay K 8644 in a supra‐additive fashion. In experiments conducted in the reversed condition, Bay K 8644 (1 nM but not 10 nm) potentiated the effect of verapamil in a similar manner but to a lesser extent.
It is concluded that verapamil, in contrast to nifedipine, markedly enhances neurally‐evoked twitches of the mouse vas deferens. Bay K 8644 produces essentially the same effect as verapamil, but its potency is 1000 fold and its maximal effect about 3 fold greater than that observed for verapamil. It is suggested that the mechanism of twitch potentiation by verapamil is different from that of Bay K 8644 and may involve an increased release of non‐adrenergic co‐transmitter(s).
Cardiovascular interactions between vasopressin, angiotensin and noradrenaline in the Brattleboro rat
Authors: Laycock J.F. , Lightman S.L. 
Published: July 2012

The cardiovascular effects of bolus intravenous injections of vasopressin, angiotensin II and noradrenaline were studied in 6‐hydroxydopamine pretreated, anaesthetized Brattleboro rats with hereditary diabetes insipidus and normal rats of the parent Long Evans strain.
Pretreatment with 6‐hydroxydopamine did not significantly affect control values for mean arterial blood pressure, cardiac output or total peripheral resistance in either Brattleboro or Long Evans rats but the pressor response to haemorrhage was reduced in both strains compared to the control animals.
The pressor responses of the untreated Brattleboro rats to 250 mu kg−1 vasopressin were significantly greater and more prolonged than in control rats of the Long Evans strain.
Pretreatment with 6‐hydroxydopamine significantly enhanced the peak pressor response to vasopressin, but not to angiotensin II (1 μg kg−1), in Brattleboro and Long Evans rats.
Pretreatment with 6‐hydroxydopamine resulted in an enhanced pressor response to 1 μg kg−1 noradrenaline in both Brattleboro and Long Evans rats, but the effect was significantly greater in the vasopressin‐deficient animals.
These results indicate differences in the pressor responsiveness of Brattleboro rats to vasopressin and noradrenaline, but not to angiotensin II, compared with control Long Evans rats and provide evidence for important interactions between the sympathetic nervous system and these pressor hormones.
Endotoxin‐induced hyperreactivity of the guinea‐pig isolated trachea coincides with decreased prostaglandin E2 production by the epithelial layer
Authors: Folkerts Gert , Engels Ferdi , Nijkamp Frans P. 
Published: July 2012

Pretreatment of guinea‐pigs with endotoxin (1 mg kg−1 b.w., i.p., 4 days before the experiments) results in respiratory airway hyperreactivity in vitro. Dose‐response curves with either arecoline or histamine on isolated tracheae from these animals display increased maximal contractions, and decreased EC50 values.
Tracheae denuded of epithelium respond with a similar hyperreactivity to histamine as observed in preparations from endotoxin pretreated animals. Removal of the epithelial layer of tracheae from endotoxin pretreated guinea‐pigs did not additionally affect the histamine dose‐response curve.
The cyclo‐oxygenase inhibitor indomethacin (10 μm) induces histamine hyperreactivity which is equal in intact and epithelium‐denuded tracheae from saline or endotoxin pretreated guinea‐pigs. Similar results are obtained with the combined lipoxygenase/cyclo‐oxygenase inhibitor nordihydroguaiaretic acid (10 μm).
Histamine (0.1 mm) induces an increase in prostaglandin E2 (PGE2) formation by the tracheal spiral in vitro, which is reduced by 34% by endotoxin pretreatment, and by about 60% following epithelium removal irrespective of endotoxin pretreatment.
Arachidonic acid (AA, 22 μm) stimulation of the guinea‐pig trachea in vitro induces a relaxation, and an increase in PGE2 production. In preparations lacking the epithelium, AA induces a contraction which coincides with a 60% reduced increase in PGE2 formation. These effects are not altered by endotoxin pretreatment.
It is concluded that the endotoxin‐induced respiratory airway hyperreactivity may be caused by a disturbed ability of epithelial cells to synthesize PGE2. The decreased formation of this prostaglandin is rather the consequence of a diminished liberation of AA from the phospholipid stores than a dysfunction of the cyclo‐oxygenase enzyme.
Monoamine oxidase activity and triiodothyronine biosynthesis in human cultured thyroid cells
Authors: Kraiem Z. , Sadeh O. , Youdim M.B.H. 
Published: July 2012

The proposal that monoamine oxidase (MAO) is a source of peroxide in thyroid hormone biosynthesis has been examined by use of isolated cultured human thyroid cells which retain the ability to secrete triiodothyronine (T3) in response to thyroid stimulating hormone (TSH).
The results demonstrated the presence of MAO A and B in human thyroid cells which oxidized 5‐hydroxytryptamine and 2‐phenylethylamine, respectively, and were selectively inhibited by the MAO inhibitors clorgyline and (−)‐deprenyl.
Addition of propylthiouracil to the culture system induced a 61% reduction in TSH‐stimulated T3 secretion, indicating that the bulk of such secretion apparently derives from de novo iodothyronine synthesis.
The MAO A and B substrate, tyramine, was ineffective in stimulating T3 secretion.
The selective MAO inhibitors, clorgyline and (−)‐deprenyl, alone and in combination, and in the presence and absence of tyramine, failed to inhibit basal as well as TSH‐stimulated T3 secretion in cultured human thyrocytes.
It is therefore apparent that even though thyroid MAO A and B enzyme reactions result in the generation of H202, this H202 does not seem to play a significant role in T3 biosynthesis.
The effects of vasoactive intestinal peptide (VIP) antagonists, and VIP and peptide histidine isoleucine antisera on non‐adrenergic, non‐cholinergic relaxations of tracheal smooth muscle
Authors: Ellis James L. , Farmer Stephen G. 
Published: July 2012

The effects of several drugs, including antagonists of vasoactive intestinal peptide (VIP), and antisera to VIP or peptide histidine isoleucine (PHI), on relaxation responses of guinea‐pig isolated trachea to electrical field stimulation (EFS) have been examined.
β‐Adrenoceptor blockade with propranolol only partially blocked the inhibitory response to EFS, but had no effect in tissues from animals pretreated with 6‐hydroxydopamine or reserpine.
Neither adenosine deaminase, in the presence of dipyridamole, nor the potent adenosine antagonist NPC205 (1,3‐n‐dipropyl‐8‐(4‐hydroxyphenyl)‐xanthine) had any effect on the inhibitory response to EFS.
The VIP antagonists, [Ac‐Tyr1, d‐Phe2]‐GRF(1–29)‐NH2 and [4‐Cl‐d‐Phe6, Leu17]‐VIP had no effect on the inhibitory response to EFS. Moreover, they were without effect on responses to exogenous VIP or PHI.
Overnight incubation with VIP antisera markedly reduced the inhibitory response to EFS. PHI antisera had a similar, but smaller effect.
In the presence of a concentration of VIP that is maximal for its relaxant effect, inhibitory responses to electrical stimulation were greatly inhibited.
Naloxone and reactive blue 2 each had no effect on inhibitory responses indicating that endogenous opioids and adenosine 5′‐triphosphate (ATP) respectively are not involved.
The results suggest that VIP and PHI, but not adenosine, contribute to non‐adrenergic, non‐cholinergic inhibitory nerve responses of guinea‐pig trachea. Moreover, the surprising lack of effect of both VIP antagonists on these responses, and in particular, on responses to exogenous VIP, suggests that the receptors mediating VIP‐induced tracheal relaxation are different from those that mediate pancreatic secretion.
α2‐Adrenoceptor agonists enhance responses to certain other vasoconstrictor agonists in the rat tail artery
Authors: Xiao Xiao‐Hui , Rand Michael J. 
Published: July 2012

The effects of the α2‐adrenoceptor agonists clonidine, rilmenidine, TL99 and UK14304 on the vasoconstrictor response to sympathetic nerve stimulation and on the concentration‐response curves to noradrenaline and phenylephrine were compared in two isolated, perfused vascular tissues: the rat tail artery (which has both postjunctional α1‐ and α2‐adrenoceptors), and the rabbit ear artery (in which only α1‐adrenoceptors are present postjunctionally).
In the rabbit ear artery, the first observable effect of α2‐adrenoceptor agonists was inhibition of vasoconstrictor responses to sympathetic nerve stimulation. This occurred with concentrations of the α2‐adrenoceptor agonists which were far below those producing vasoconstriction. Responses to noradrenaline were not affected.
In contrast, in the rat isolated perfused tail artery, α2‐adrenoceptor agonists, in concentrations that produced no other observable effects, enhanced the vasoconstrictor responses to sympathetic nerve stimulation and to noradrenaline. Much higher concentrations of α2‐adrenoceptor agonists produced vasoconstriction in most preparations and only then reduced the response to sympathetic nerve stimulation. The enhancing effect of α2‐adrenoceptor agonists was blocked by idazoxan, but not by prazosin.
Vasoconstrictor responses in the rat tail artery to the relatively selective α1‐adrenoceptor agonist phenylephrine were enhanced by α2‐adrenoceptor agonists. The enhancement of the response to phenylephrine was greater than that to the mixed α1‐ and α2‐adrenoceptor agonist noradrenaline.
Vasoconstrictor responses in the rat tail artery to vasopressin, ATP and KCl, like those to α1‐adrenoceptor agonists, were enhanced by α2‐adrenoceptor agonists. However, vasoconstrictor responses to 5‐hydroxytryptamine and angiotensin II were not enhanced.
Measurement of 3‐methoxy‐4‐hydroxyphenylglycol (MHPG) in mouse brain by h.p.l.c. with electrochemical detection, as an index of noradrenaline utilisation and presynaptic α2‐adrenoceptor function
Authors: Heal D.J. , Prow M.R. , Buckett W.R. 
Published: July 2012

A novel method for measurement of 3‐methoxy‐4‐hydroxyphenylglycol (MHPG) in mouse brain by use of high performance liquid chromatography (h.p.l.c.) with electrochemical detection is described. This technique incorporates an ethyl acetate purification procedure and uses 3‐hydroxy‐4‐methoxyphenylglycol (iso‐MHPG) as the internal standard.
Inhibition of monoamine oxidase by injection of tranylcypromine (5 and 10 mg kg−1) or pargyline (50 and 100 mg kg−1) markedly decreased brain MHPG concentrations. After injection of the tyrosine hydroxylase inhibitor, α‐methyl‐p‐tyrosine (200 mg kg−1), there were time‐dependent linear decreases in the concentrations of noradrenaline and MHPG in mouse brain. In addition, a very good correlation (r = 0.95, n = 30; P < 0.001) was found between the concentrations of noradrenaline and MHPG present in the brains of the same mice after α‐methyl‐p‐tyrosine treatment.
Mouse brain MHPG concentrations were dose‐dependently reduced after administration of the α2‐adrenoceptor agonist, clonidine (1–3000 μg kg−1), and elevated by the antagonists, idazoxan (1 and 5 mg kg−1), and yohimbine (1 and 5 mg kg−1). Intracerebroventricular injection of the α1‐adrenoceptor agonist, phenylephrine (5–50 μg) dose‐dependently increased MHPG levels. The α1‐adrenoceptor antagonist, prazosin, had no effect at the moderate dose of 1 mg kg−1, but increased MHPG concentrations at 5 mg kg−1. The β‐adrenoceptor agonist, clenbuterol (10–1000 μg kg−1) and the antagonist, pindolol (1 and 5 mg kg−1), were both without effect.
The decrease in brain MHPG concentrations induced by clonidine (100 μg kg−1) was prevented by prior injection of 1 mg kg−1 of idazoxan or yohimbine, but not by prazosin or pindolol.
MHPG levels were decreased after administration of the noradrenaline reuptake inhibitor desipramine (5 and 10 mg kg−1) and the non‐selective monoamine reuptake inhibitors, sibutramine HCl (BTS 54 524; 1 and 3 mg kg−1) and amitryptyline (5 mg kg−1). However, the selective 5‐hydroxytryptamine reuptake inhibitor, zimeldine (5 and 10 mg kg−1), was without effect. Dexamphetamine (1 and 5 mg kg−1) and methamphetamine (1 and 5 mg kg−1) both decreased brain MHPG concentrations in a dose‐related fashion.
Overall the data show that MHPG can be used as a functional index of both presynaptic α2‐adrenoceptor activity and noradrenaline turnover and utilisation.
Histamine release in the isolated vascularly perfused stomach of the rat: regulation by autoreceptors
Authors: Sandvik Arne K. , Lewin Miguel J.M. , Waldum Helge L. 
Published: July 2012

In the isolated vascularly‐perfused stomach of the rat, gastrin 1–17 (520 pmol l−1) increased acid output from basal values of 13.7 ± 2.7 to 92.5 ± 11.4 μmol h−1 and venous histamine output from 10.1 ± 2.3 to 54.7 ± 7.9 nmol h−1 (mean ± s.e.mean).
The H1 receptor agonist 2‐methylhistamine (10 μmol l−1) increased acid output to 21.6 ± 2.9 μmol h−1 (P < 0.05) and reduced basal histamine output to 4.0 ± 0.8 nmol h−1 (P < 0.05). Gastrin‐stimulated acid secretion and vascular histamine output was not significantly affected by 2‐methylhistamine (10 μmol l−1).
The H2 receptor agonist, impromidine, dose‐dependently increased basal acid secretion, reaching a maximal value of 145.5 ± 11.7 μmol h−1 with impromidine (10 μmol l−1), and maximal gastrin‐stimulated acid secretion to 167.4 ± 15.1 μmol h−1 with impromidine (10 μmol l−1). Impromidine dose‐dependently inhibited basal and gastrin‐stimulated vascular histamine output.
The H3 receptor agonist R‐a‐methylhistamine, (1 and 10 μmol l−1) minimally increased basal acid secretion. R‐a‐methylhistamine (10 μmol l−1) did not significantly affect maximal gastrinstimulated acid secretion. Basal and gastrin‐stimulated vascular histamine outputs decreased to 4.0 ± 0.8 (P < 0.05) and 24.7 ± 4.7 nmol h−1 (P = 0.05) with R‐a‐methylhistamine (10 μmol 1−1).
The H2 receptor antagonist ranitidine (2 μmol l−1) did not inhibit basal acid secretion, but acid outputs with gastrin and all histamine agonists were reduced. Ranitidine did not affect histamine release in the basal state, with gastrin or with any histamine agonist tested.
We conclude that gastric histamine release in the rat is regulated via a histamine H2 receptor sensitive to the histamine agonists tested, but not to ranitidine. It is unlikely that the inhibition of histamine release is secondary to increased gastric acidity.
Nedocromil sodium inhibits the A23187‐ and opsonized zymosan‐induced leukotriene formation by human eosinophils but not by human neutrophils
Authors: Bruijnzeel P.L.B. , Hamelink M.L. , Kok P.T.M. , Kreukniet J. 
Published: July 2012

Inflammatory cells such as eosinophils and neutrophils are thought to contribute actively to the pathogenesis of asthma by the release of bronchoconstrictor mediators including leukotrienes. Previous studies have revealed the almost exclusive synthesis of leukotriene C4 (LTC4) by human eosinophils and of leukotriene B4 (LTB4), 20‐OH‐LTB4 and the non‐enzymatically formed LTB4‐isomers by neutrophils when stimulated in vitro with the calcium ionophore A23187 or opsonized zymosan (OZ). In this study we have investigated whether nedocromil sodium, a new anti‐asthma drug, was capable of inhibiting A23187‐ and OZ‐induced leukotriene formation by these cells.
Nedocromil sodium inhibited A23187‐ and OZ‐induced LTC4 formation by eosinophils in a concentration‐dependent manner (mean IC30 for A23187: 5.6 × 10−5m; mean IC30 for OZ: 6.3 × 10−5 m), whereas it did not inhibit A23187‐ and OZ‐induced LTB4 formation by neutrophils.
Extension of the preincubation time of the cells with the drug did not alter the observed inhibitory capacity. The optimal preincubation time was 5 min.
The in vitro inhibition of LTC4 formation by eosinophils by nedocromil sodium may be a valuable property of this drug in the treatment of asthma.