bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impairment of protein synthesis in the rat uterus following intrauterine delivery of indomethacin
Authors: Hurst P.R. , Peplow P.V. 
Published: July 2012

When indomethacin was incorporated into a slow‐release preparation (initial content 1.6 mg drug) and placed in one horn of the rat uterus, a significant decrease in protein synthesis occurred for this horn in comparison with control animals (as determined by the incorporation of radioactive leucine) at three different times after insertion. Decreases of 20, 21 % at the two times of dioestrus and 28% at the time of oestrus selected were determined. No significant reduction in protein synthesis was found for the contralateral horn, although there was a tendency for it to be lowered at the earliest time of examination when two complete oestrous cycles had passed following insertion.
Measurement of the uptake of radioactive leucine by the uterine horns showed no change in response to indomethacin delivery compared to the control animals with silastic implants, and suggested that the transport system for this amino acid in cells of the uterine horns was not affected by the drug.
It was apparent that in instances when the protein synthesis of the uterine horn was impaired by indomethacin that a decrease in RNA/DNA ratio existed. At the latest time examined, no alteration in DNA content occurred in the indomethacin‐influenced horn but there was a significant reduction in RNA content.
For a small proportion of the animals with indomethacin‐releasing preparations there was a tendency to show a lengthening of the oestrous cycle over the first three cycles following insertion. Whether this was due to a direct effect of indomethacin on the ovaries or an effect caused by decreased concentrations of prostaglandins in the uterus was unknown.
These results provide further evidence that non‐steroidal anti‐inflammatory drugs can interfere with the synthesis of macromolecular substances, and that such changes need to be taken into account when considering the overall effect of these drugs on tissues and organs.
Kinetics of the generation and action of chemical mediators in zymosan‐induced inflammation of the rabbit peritoneal cavity
Authors: Forrest M.J. , Jose P.J. , Williams T.J. 
Published: July 2012

Acute inflammation was induced by intraperitoneal injection of zymosan (yeast cell walls) in the rabbit.
Peritoneal inflammation was monitored by the local accumulation of intravenously‐injected Evans blue dye (which binds to plasma albumin) and of polymorphonuclear leukocytes (PMNLs).
The zymosan‐induced exudate fluid contained a microvascular permeability‐increasing factor or factors which, unlike histamine and bradykinin, had a long duration of action when tested in rabbit skin and was dependent on circulating PMNLs.
Using radioimmunossay, high levels of rabbit C5a, or C5a des Arg, were detected in the exudate fluid and accounted for much of the permeability‐increasing activity, as judged by skin bioassay after separation on Sephadex G‐100.
The vasodilator prostaglandin, prostaglandin I2 (PGI2), was generated in the inflammatory reaction, as judged by the presence of high levels of 6‐oxo‐PGF1α detected in the exudate by radioimmunossay. However, in contrast to observations in rabbit skin, inhibition of prostaglandin generation had a relatively small effect on peritoneal oedema formation.
C5a and C5a des Arg increase microvascular permeability by a PMNL‐dependent mechanism in the rabbit. However, in response to zymosan, protein leakage was detected considerably earlier than PMNL accumulation. A hypothesis to account for this difference is proposed.
Presynaptic muscarinic and α‐adrenoceptor‐mediated regulation of GABA release from my enteric neurones of the guinea‐pig small intestine
Authors: Hashimoto S. , Tanaka C. , Taniyama K. 
Published: July 2012

The effects of cholinomimetic and sympathomimetic drugs on the release of [3H]‐γ‐aminobutyric acid ([3H]‐GABA) evoked by high K+ from the isolated small intestine of the guinea‐pig were investigated, in the presence of tetrodotoxin.
Acetylcholine and oxotremorine, at concentrations ranging from 10−9 to 10−6 M inhibited the evoked release of [3H]‐GABA in a concentration‐dependent manner, while nicotine was without effect. Scopolamine and pirenzepine inhibited the effect of oxotremorine, while hexamethonium had no effect. The IC50 values for scopolamine and pirenzepine of the oxotremorine (3 × 10−8 M)‐induced inhibition were 1.02 × 10−9 M and 9.78 × 10−10 M, respectively.
Noradrenaline, but not isoprenaline inhibited the evoked release of [3H]‐GABA. Clonidine (10−10 − 10−6 M) reduced the evoked release of [3H]‐GABA in a concentration‐dependent manner, but phenylephrine had no effect. The inhibitory effect of clonidine was antagonized by yohimbine but not by prazosin.
These findings provide evidence for the localization of M1‐ muscarinic and α2‐ adrenoceptors on GABAergic nerve terminals and their involvement in the presynaptic control of the release of GABA from the guinea‐pig small intestine.
Electrophysiology of neuroeffector transmission in the isolated, innervated trachea of the guinea‐pig
Authors: McCaig Dorothy J. 
Published: July 2012

Intracellular recordings were made from cells of the guinea‐pig trachealis muscle. Some cells were electrically quiescent while others exhibited spontaneous slow waves.
In quiescent cells, stimulation of the cervical vagus nerve evoked transient depolarization. Occasionally there was a single depolarization, but more often there were several fluctuations in potential.
In spontaneously active cells, vagal stimulation induced a transient increase in amplitude of the slow waves without affecting their frequency.
Depolarizing responses could be obtained with a single pulse applied to the vagus nerve, and responses increased in amplitude with number of pulses (up to 16 pulses), and with frequency of stimulation (up to 20 Hz). Depolarization did not give rise to spike discharge.
Responses to vagal stimulation were blocked by atropine.
In the presence of neostigmine, vagally‐mediated depolarization was augmented and abortive spikes were observed in a number of cells.
In quiescent cells, repetitive stimulation of the sympathetic stellate ganglion evoked slight hyperpolarization.
In spontaneously active cells, sympathetic stimulation evoked attenuation, or temporary cessation of slow wave discharge, with or without hyperpolarization.
Sympathetic‐induced hyperpolarization and suppression of slow waves were both blocked by propranolol, but unaffected by phentolamine.
Electrical changes associated with sympathetic stimulation may be of minor importance in the initiation of relaxation.
Abnormal vascular phosphoinositide hydrolysis in the spontaneously hypertensive rat
Authors: Heagerty A.M. , Ollerenshaw J.D. , Swales J.D. 
Published: July 2012

The production of [3H]‐inositol phosphates was studied in labelled segments of aorta from spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) controls at 5 and 19 weeks, either unstimulated or in the presence of noradrenaline.
Basal hydrolysis of inositol phospholipids was significantly enhanced in young SHR (P < 0.05) compared to controls but this difference was no longer detected at 19 weeks.
Noradrenaline increased [3H]‐inositol phosphate accumulation in both SHR and WKY, but maximal hydrolysis was significantly greater in WKY (P < 0.01), although the ED50 was similar in both groups of animals.
These data demonstrate that phosphatidylinositide hydrolysis is enhanced in the young hypertensive rat at the time blood pressure is rising, but that this activity has declined by the time hypertension has reached an established phase. In addition, α1‐agonist induction of inositol phospholipid hydrolysis differs in the two species of animals, being reduced in genetically mature hypertensive rats.
The effect of angiotensin II upon electrogenic ion transport in rat intestinal epithelia
Authors: Cox H.M. , Cuthbert A.W. , Munday K.A. 
Published: July 2012

Epithelial sheets from rat jejunum and descending colon have been shown to respond to angiotensin II (AII) when studied under short‐circuit conditions and bathed on both sides with Krebs‐Henseleit solution.
The octapeptide AII elicited increases in short‐circuit current (SCC) in preparations of jejunum and decreases in SCC in the descending colon; both responses occurred when the peptide was applied to the basolateral surface, but not when applied to the apical solution.
Responses in both tissues were highly specific, being inhibited by a range of AII antagonists with the following order of potency: [Sar1. Thr8]‐AIi>[Sar1. Leu8]‐AIi>[Sar1. Ile8]‐AIi>[Sar1. Ala8]‐AIi>[Des, Asp1. Ile8]‐AII in rat jejunum. AII responses were not affected by α‐or β‐adrenoceptor antagonists, atropine or tetrodotoxin.
AII responses were totally inhibited by the chloride channel blocker, diphenylamine‐2‐carboxylate (DPC) while cotransport inhibitors e.g. piretanide and frusemide significantly reduced the size of AII responses in colon and jejunum. These patterns of activity suggest that in the jejunum the responses result from electrogenic chloride secretion. Although AII responses in colon were sensitive to DPC the transporting ions have not yet been identified.
Both piroxicam and indomethacin inhibited the increase in SCC elicited by AII in the jejunum, and the reduction in SCC caused by AII in the colon. Taken together these results indicate that eicosanoids are involved in AII responses in both tissues.
This is the first study to demonstrate a direct, electrogenic effect for AII on transporting epithelia from the gastrointestinal tract. The responses are most probably initiated by AII interacting with previously identified specific AII receptors within the epithelial membranes.
The adenosine receptor‐mediated inhibition of noradrenaline release possibly involves a N‐protein and is increased by α2‐autoreceptor blockade
Authors: Allgaier Clemens , Hertting Georg , Kügelgen Oda V. 
Published: July 2012

The stimulation‐evoked overflow of [3H]‐noradrenaline from slices of the rabbit hippocampus is inhibited by α2‐autoreceptors as well as by adenosine (A1)‐receptors. Slices of rabbit hippocampus were labelled with [3H]‐noradrenaline, superfused continuously and stimulated twice electrically (rectangular pulses; 2 ms, 3 Hz, 24 mA, 5 V cm−1).
Treatment of hippocampal slices with N‐ethylmaleimide (NEM, 30 μm; 30 min), which functionally disturbs certain N‐proteins, decreased the inhibitory action of adenosine receptor agonists like (‐)‐N6‐(R‐phenylisopropyl)‐adenosine ((‐)‐PIA) and adenosine on noradrenaline release. Release inhibition caused by (‐)‐PIA (0.03‐1 μm) was antagonized by NEM in a non‐competitive manner in the absence and in the presence of the α2‐adrenoceptor antagonist yohimbine.
The adenosine receptor antagonist 8‐phenyltheophylline significantly increased the evoked noradrenaline release by about 15% in control slices by diminishing the inhibitory action of endogenous adenosine. In NEM‐treated slices this effect of 8‐phenytheophylline was not seen. In the presence of (‐)‐PIA (0.1 μm), i.e. under conditions of an increased inhibitory tone, release facilitation by 8‐phenyltheophylline was decreased by NEM compared to that in the respective controls.
Occupation of the A1‐receptor with (‐)‐PIA prior to and during the NEM treatment did not protect the A1‐receptor‐coupled signal transduction system from being affected by NEM.
In the presence of the α2‐adrenoceptor antagonist yohimbine, the inhibitory action of (‐)‐PIA was strongly increased.
The above results suggest the involvement of a regulatory N‐protein in the A1‐receptor‐mediated inhibition of noradrenaline release and an interaction between the α2‐autoreceptor and the A1‐receptor‐coupled signal transduction system, possibly at the level of a N‐protein.
The obligatory role of calcium in the development of antigen‐induced airway hyperreactivity to cold provocation in the rat isolated trachea
Authors: Chand N. , Diamantis W. , Sofia R.D. 
Published: July 2012

The effect of antigen challenge on cold provocation (30‐10°C) in isolated tracheal segments from control (normal) and ovalbumin‐sensitized rats was studied.
Sensitization alone or acute cold provocation (10°C) alone was not sufficient to cause contraction of tracheal smooth muscle preparation.
Following recovery from antigen‐induced responses (Schultz‐Dale phenomenon) in sensitized rat segments, cold provocation induced strong contractile responses.
Both the antigen‐induced contractions and the subsequent development of airway hyperreactivity to cold were dependent on extracellular Ca2+ and inhibited by verapamil.
The data in this study indicate that extracellular Ca2+ plays an obligatory role in the mediation of antigen‐induced contractile responses as well as the subsequent development of hyperreactivity to cold provocation in rat tracheal smooth muscle.
Calcitonin gene‐related peptide is localised to human airway nerves and potently constricts human airway smooth muscle
Authors: Palmer James B.D. , Cuss Francis M.C. , Mulderry Peter K. , Ghatei Mohamed A. , Springall David R. , Cadieux Alain , Bloom Stephen R. , Polak Julia M. , Barnes Peter J. 
Published: July 2012

In human airways synthetic human sequence calcitonin gene‐related peptide (hCGRP), a novel peptide produced by alternative processing of mRNA from the calcitonin gene, caused concentration‐dependent contraction of human bronchi (EC50 4.9 × 10−9 m) and was significantly more potent than substance P or carbachol.
The contractile response was unaffected by atropine (2 × 10−6 m), propranolol (10−6 m), indomethacin (10−5 m), tetrodotoxin (3 × 10−6 m), chlorpheniramine (10−4 m), cimetidine (10−5 m), or FPL55712 (10−4 m) suggesting a direct effect of CGRP on airways smooth muscle.
CGRP was detected in human airways by radioimmunoassay with highest concentrations in cartilaginous airways.
CGRP was localised by immunocytochemistry to both nerves and ganglia in human airways.
CGRP, is a potent constrictor of human airways and may have important effects on airway function and be implicated in the pathogenesis of bronchial hyper‐responsiveness and asthma.
Absence of effect of calcium antagonists on endothelium‐dependent relaxation in rabbit aorta
Authors: Jayakody R.L. , Kappagoda C.T. , Senaratne M.P.J. , Sreeharan N. 
Published: July 2012

The effect of chronic feeding of New Zealand White rabbits with nicardipine (60 mg kg−1 daily for 5 weeks) on the endothelium‐dependent relaxation (EDR) to acetylcholine (ACh) was examined in vitro. The effect of acute exposure to nicardipine and diltiazem (10 μmol l−1) in the tissue bath was also examined.
A bioassay system for endothelium‐dependent relaxation factor (EDRF) in which a rabbit aortic ring with endothelium removed was used as recipient and a segment of rabbit aorta with endothelium as donor (producing EDRF in response to ACh) was developed. This system enabled the effect of nicardipine on the synthesis/release and on the relaxation to EDRF to be studied separately.
The maximum relaxations to ACh in control and nicardipine‐fed animals were 43.6 ± 5.5 and 53.8 ± 6.7% (mean ± s.e.mean) of the contractile response to noradrenaline (NA, 1 μmol l−1) (n = 6, P > 0.05). Similarly the EDR to ACh was not significantly altered by acute exposure (30 min) to nicardipine or diltiazem. The maximum relaxations without and with nicardipine were 32.4 ± 4.2% and 28.0 ± 3.1% of the contraction to NA (1 μmol l−1) (n = 11, P > 0.05). The corresponding data for diltiazem were 42.1 ± 5.7 and 36.4 ± 7.3% respectively (n = 11, P > 0.05).
Both calcium antagonists inhibited the contraction induced by potassium (100 mmol l−1). Nicardipine and diltiazem in concentrations of 100 μmol l−1 reduced the potassium‐induced contraction to 33.0 ± 9.0% and 53.8 ± 6.7% of control respectively (n = 6, P < 0.05).
In the bioassay experiments the infusion of nicardipine on (a) the recipient tissue only and (b) the donor and the recipient tissue had no significant effect on the relaxant response observed in the recipient tissue when superfused with Krebs‐bicarbonate buffer containing ACh via the donor tissue (n = 6, P > 0.05).
These results indicate that nicardipine and diltiazem had no significant effect on synthesis/release and the relaxant response to EDRF in the rabbit aorta. Thus the translocation of Ca2+ accompanying the EDR to ACh in the rabbit aorta is likely to utilize Ca2+ channels not blocked by these calcium antagonists.
The involvement of platelet activating factor in endotoxin‐induced pulmonary platelet recruitment in the guinea‐pig
Authors: Beijer L. , Botting J. , Crook P. , Oyekan A.O. , Page C.P. , Rylander R. 
Published: July 2012

Exposure of conscious guinea‐pigs to an aerosol of endotoxin (25–100 μg ml−1) resulted in a dose‐related, progressive accumulation of platelets in the thoracic region. Accumulation of 111indium oxine labelled erythrocytes was not observed following exposure to an aerosol of endotoxin (50 μg ml−1).
Pretreatment of guinea‐pigs with the selective platelet activating factor (Paf)‐antagonists. CV‐3988 or brotizolam resulted in a dose‐related inhibition of endotoxin‐induced pulmonary platelet recruitment. Pretreatment of guinea‐pigs with the selective Paf‐antagonist BN 52021 resulted in significant inhibition of endotoxin‐induced pulmonary platelet recruitment, although the effects of BN 52021 were not dose‐related.
Pretreatment of guinea‐pigs with indomethacin at doses known to inhibit cyclo‐oxygenase did not inhibit endotoxin‐induced pulmonary platelet recruitment, whereas higher doses of indomethacin produced a reduction in platelet recruitment in the lung.
Pretreatment of guinea‐pigs with the anticoagulant heparin and the prostacyclin analogue ZK 36374 inhibited endotoxin‐induced platelet recruitment.
These observations suggest that endotoxin‐induced pulmonary platelet recruitment in the guinea‐pig is secondary to the release of platelet activating factor, but not to cyclo‐oxygenase products of arachidonic acid and may also involve activation of the coagulation cascade.
Decreased responsiveness of the aortae of hypertensive rats to acetylcholine, histamine and noradrenaline
Authors: Sim M.K. , Singh M. 
Published: July 2012

The responses to noradrenaline (NA) of the aortae of various hypertensive rats, namely the spontaneously hypertensive rat (SHR), the low blood pressure SHR (LBP‐SHR), and the left renal artery stenosed LBP‐SHR (LRAS‐LBR‐SHR), were compared to those of the normotensive Wistar‐Kyoto rats (WKY).
The aortae of the hypertensive rats were significantly more responsive (P <0.05) to 10−8 m NA. However, the reverse was true for higher doses of NA. The ED50 values for the aortae of WKY, LBP‐SHR, SHR and LRAS‐LBP‐SHR were 20, 8.5, 7.8 and 8 nM respectively.
The NA‐contracted aortae of the LRAS‐LBP‐SHR were significantly less responsive (P < 0.05) to the relaxant action of histamine and acetylcholine (ACh) compared to those of the WKY. This observation was not made in the aortae of the LBP‐SHR. The maximal relaxation (% of the maximal contraction induced by 10−8 m NA) observed in the aortae of WKY, LBP‐SHR and LRAS‐LBP‐SHR were, respectively, 72 ± 2, 66 ± 6, 39 ± 7 for ACh and 50 ± 3, 36 ± 4, 27 ± 3 for histamine.
In aortae where the endothelium had been removed by collagenase treatment, histamine induced a dose‐related contraction. The rank order of this dose‐related contraction was WKY > LBP‐SHR > SHR> LRAS‐LBP‐SHR with the corresponding maximal tension (g) 0.89 ± 0.04, 0.59 ± 0.04, 0.36 ± 0.04, 0.19 ± 0.05.
The results suggested that elevation of blood pressure above the normal (due either to intrinsic or extrinsic factors), as seen in SHR and LRAS‐LBP‐SHR, results in a decreased response of the aortae to ACh and histamine. This effect was seen in both the endothelium mediated relaxation and the non‐endothelium mediated contraction.
Influence of 5‐hydroxytryptamine uptake on the apparent 5‐hydroxytryptamine antagonist potency of metoclopramide in the rat isolated superior cervical ganglion
Authors: Ireland S.J. , Straughan D.W. , Tyers M.B. 
Published: July 2012

Metoclopramide, 1 × 10−6−1 × 10−4 m, was found to behave as a reversible, competitive antagonist of 5‐hydroxytryptamine (5‐HT)‐induced depolarization of the rat isolated vagus nerve (VN) and superior cervical ganglion (SCG). The pKB values were 6.60 (± 0.04) and 5.74 (± 0.07), respectively. The possibility that this apparent difference in potency was due to saturable 5‐HT uptake was investigated.
The SCG, but not the VN, accumulated tritium‐labelled 5‐HT via a saturable, sodium‐ and temperature‐dependent mechanism. Ganglionic 5‐HT uptake was blocked by desmethylimipramine (IC50 1.4 × 10−6 m), chlorimipramine (8.7 × 10−9 m), zimelidine (1.5 × 10−7 m), paroxetine (4.3 × 10−8 m) and citalopram (6.2 × 10−8 m).
The 5‐HT uptake inhibitor paroxetine, 1 × 10−6 m, did not modify the apparent 5‐HT antagonist potency of metoclopramide on the VN, but raised the pKB obtained against 5‐HT on the SCG from 5.74 (± 0.07) to 6.25 (± 0.03).
It is suggested that the observed difference in the potency of metoclopramide as a 5‐HT antagonist on the rat VN and SCG was due to saturable 5‐HT uptake in the latter preparation. The results do not support a difference in the 5‐HT receptors mediating depolarization on the VN and SCG.
Pharmacological characterization of 5‐hydroxytryptamine‐induced depolarization of the rat isolated vagus nerve
Authors: Ireland S.J. , Tyers M.B. 
Published: July 2012

A study has been made of the pharmacology of the 5‐hydroxytryptamine (5‐HT)‐induced depolarization responses that can be recorded extracellularly from the rat isolated cervical vagus nerve.
Phenylbiguanide (PBG) and 2‐methyl‐5‐hydroxytryptamine (2‐methyl‐5‐HT) were found to mimic the effects of 5‐HT on the vagus nerve. Their EC50 values were respectively 2.0 fold and 3.9 fold greater than that of 5‐HT.
Metoclopramide behaved as a reversible competitive antagonist of depolarization induced by PBG and 2‐methyl‐5‐HT, with pKB values of 6.48 ± 0.04 and 6.64 ± 0.04, respectively. These agreed well with the pKB value of 6.60 ± 0.04 obtained previously for metoclopramide against 5‐HT on the rat vagus nerve. 5‐HT, PBG and 2‐methyl‐5‐HT had no demonstrable agonist effects at non‐5‐HT receptors on the rat vagus nerve.
Tropacaine and m‐chlorophenylpiperazine were found to behave as reversible competitive antagonists of 5‐HT‐induced depolarization of the vagus nerve. The pKB values were 6.29 ± 0.03 and 6.90 ± 0.03, respectively.
Quipazine, MDL 72222 and ICS 205–930 were also shown to be effective antagonists of 5‐HT on the vagus nerve. However, although these compounds were highly potent, they all caused a marked concentration‐dependent reduction in the amplitude of the maximum response to 5‐HT. This behaviour was not consistent with a simple reversible competitive mechanism.
The results are discussed with reference to the current classification of mammalian peripheral neuronal 5‐HT receptors.