bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maintained contractions of rat uterine smooth muscle incubated in a Ca2+‐free solution
Authors: Mironneau C. , Mironneau J. , Savineau J.P. 
Published: July 2012

The effects of acetylcholine (10−4m), prostaglandin E2 (10−6m), vanadate (5 × 10−4m) and fluoride (10−2m) have been studied on the mechanical and electrical activities of rat myometrial strips perfused in Ca2+‐free EGTA‐containing solutions.
All four substances produced maintained contractions which could be initiated repeatedly after exposure to Ca2+‐free solution for more than 1 h, without a significant decrease. The largest contractions were obtained with vanadate and the smallest ones with acetylcholine. The tension was usually 7–30% of the control contraction triggered by an action potential in Ca2+ containing solution.
Maintained contractions induced by fluoride were unaffected by isoprenaline while those induced by acetylcholine, prostaglandin E2 and vanadate were completely relaxed.
Prostaglandin E2 ‐and vanadate‐induced contractions were slightly reduced by Na+ removal or by adding Ca2+ antagonists. In contrast, contractions induced by acetylcholine were suppressed in Na+‐free solution and largely inhibited in the presence of Ca2+ antagonists.
The depolarization induced by acetylcholine in Ca2+‐free solution was strongly dependent on the external Na+ concentration. The relationship between the size of the acetylcholine‐induced depolarization and the membrane potential (shifted by constant currents) was linear, giving an apparent reversal potential for acetylcholine close to zero potential.
In Ca‐free solutions and in the presence of atropine, Na+ action potentials of long duration can be evoked which produced contractions of the same order of magnitude as those initiated by acetylcholine‐induced depolarizations.
These results are consistent with the hypothesis that the maintained contractions in Ca2+‐free solutions induced by several stimulants could be related to Ca2+‐independent mechanisms (fluoride) or Ca2+ release from an intracellular store. This latter mechanism would include both pharmacomechanical (prostaglandin E2, vanadate) and electromechanical (acetylcholine) coupling.
Antagonism of fenfluramine‐induced hyperthermia in rats by some, but not all, selective inhibitors of 5‐hydroxytryptamine uptake
Authors: Sugrue M.F. 
Published: July 2012

The injection of fenfluramine (7.5 mg kg−1, i.p.) to rats housed at 27–28°C was associated with an elevation of core body temperature which peaked at approximately 1 h post‐injection.
One h pretreatment with Citalopram (20 mg kg−1, i.p.), chlorimipramine (10 mg kg−1, i.p.), femoxetine (10 mg kg−1, i.p.) and fluoxetine (20 mg kg−1, i.p.) resulted in an attenuated response to fenfluramine. In contrast, Org 6582 (20 mg kg−1) and zimelidine (20 mg kg−1) were devoid of an effect on fenfluramine‐induced hyperthermia. The response to fenfluramine was also blocked by i.p. injections of metergoline (0.2 mg kg−1), methysergide (5 mg kg−1) and mianserin (0.5 mg kg−1). Rectal temperature was unaltered by both the 5‐hydroxytryptamine (5‐HT) uptake inhibitors and the 5‐HT receptor antagonists.
The IC50 values (nm) for in vitro inhibition of [3H]‐5‐HT uptake into rat hypothalamic synaptosomes were for Citalopram 2.4, chlorimipramine 8.8, femoxetine 14, fluoxetine 16, Org 6582 75 and zimelidine 250. The injection of all six compounds (20 mg kg−1, i.p.) 1 h before death was associated with an inhibition of [3H]‐5‐HT uptake into rat hypothalamic synaptosomes which ranged from 47.2% for chlorimipramine to 83.3% for Citalopram.
Rat hypothalamic 5‐HT levels were decreased by approximately 50% 3 h after the injection of fenfluramine (15 mg kg−1, i.p.). This effect was blocked by a 1 h pretreatment with fluoxetine, Org 6582 and zimelidine (all 20 mg kg−1, i.p.).
Ki values for displacement of specifically bound [3H]‐5‐HT (1 nm) to rat hypothalamic membranes were for metergoline 26 nm, methysergide 1.1 μm, mianserin 3.6 μm, chlorimipramine 9.2 μm and fluoxetine 32.7 μm. Values for Citalopram, femoxetine, Org 6582 and zimelidine were in excess of 65.4 μm.
Fenfluramine‐induced hyperthermia in rats is blocked by Citalopram, chlorimipramine, femoxetine and fluoxetine but not by Org 6582 and zimelidine. This dichotomy cannot be explained in terms of differences in 5‐HT uptake, storage and release mechanisms in the rat hypothalamus. Moreover, antagonism of fenfluramine‐induced hyperthermia cannot be attributed to blockade of central, postsynaptic 5‐HT receptors. The involvement of an indoleamine other than 5‐HT is discussed.
An increase in sensitivity of rat cingulate cortical neurones to substance P occurs following withdrawal of chronic administration of antidepressant drugs
Authors: Jones Roland S.G. , Olpe Hans‐Rudolf 
Published: July 2012

The sensitivity of neurones in the cingulate cortex of the rat to iontophoretically applied substance P (SP) was tested one hour after a single dose of various antidepressant drugs and also 1 day following the termination of a chronic dosing schedule (14 once daily injections) of the same agents.
One hour after a single injection of desipramine (DMI), chlorimipramine (CMI), trimipramine (TMI) or zimelidine (ZIM) (all at 10 mg kg−1 i.p.) there was no change in the mean size of excitatory responses to SP compared to those before the injection. There was a tendency towards a decrease in the TMI group.
One day following the last of 14 consecutive daily injections (10 mg kg−1 i.p.) of the above agents there was a significant increase in the size of excitatory responses to SP compared to those in rats receiving daily saline injections. However, 14 days of treatment with DMI did not alter the responses to l‐glutamate.
Similar chronic dosing schedules with either diazepam (5 mg kg−1) or fluphenazine (5 mg kg−1) did not affect the responses to SP.
Thus chronic but not acute administration of antidepressant drugs results in an increase in the sensitivity of neurones, in the cingulate cortex of the rat, to SP.
Pharmacological actions of some cyclic analogues of choline
Authors: Hemsworth B.A. , Shreeve S.M. , Veitch G.B.A. 
Published: July 2012

Two cyclic choline analogues (3‐hydroxy‐N,N‐dimethylpiperidinium and 2‐hydroxymethyl‐N,N‐dimethylpiperidinium) and two cyclic homocholine analogues (4‐hydroxy‐N,N‐dimethylpiperidinium and 3‐hydroxymethyl‐N,N‐dimethylpiperidinium) have been studied with regard to their actions at the cholinergic synapse.
All the analogues had some direct depolarizing activity on the frog rectus abdominis muscle but they were less potent in this respect than acetylcholine. Compared to physostigmine, the analogues were weak inhibitors of Cholinesterase enzymes.
All the analogues were found to have a presynaptic blocking action on the rat phrenic nerve‐hemidiaphragm preparation, which was reversed by choline. In addition, they all inhibited the high affinity transport of choline into synaptosomes but only the cyclic choline analogues were found to be acetylated by soluble choline acetyltransferase in vitro.
We conclude that the hydroxypiperidinium analogues caused the presynaptic block seen at the neuromuscular junction by inhibiting acetylcholine synthesis.
Genetic heterogeneity of histamine H2‐receptors in the mouse vas deferens
Authors: Calvete J. A. , Donegan J.L.M. , Hayes R.J. , Oates N.S. , Sloan T.P. 
Published: July 2012

The ability of histamine to inhibit the overall contractile (‘twitch’) response of the isolated vas deferens of the mouse to electrical field stimulation (64 V pulse, 1 ms pulse width, frequency 0.2 Hz) was studied in nine inbred mouse strains. The strains were also characterized in terms of the potency of the histamine H2‐receptor antagonist cimetidine in its inhibition of histamine‐mediated effects. An apparently bimodal inter‐strain variation (8−10 fold) in both characteristics was encountered, with three strains (SWR, A2G and C57BL/10ScSn) relatively sensitive (S) to both agonist and antagonist actions, and six (C3H, A, C57/BL6, DBA/2, Balb/C and 129/Sv) relatively insensitive (IS).
These strain differences were independent of extracellular calcium concentration in the range 1.25−5 mm, and also independent of the frequency of tissue stimulation over the range 0.2−6.4 Hz.
Representative S (SWR and A2G) and IS (DBA/2 and C3H) mouse vasa were also characterized in terms of their sensitivity to the agonist actions of dimaprit and the antagonist actions of tiotidine. In the S strain tissues, dimaprit produced 50% inhibition of the twitch response at 4.6−1.8 μm (mean ± s.d.) and was able to elicit complete inhibition of the twitch response at concentrations greater than 100 μm, whereas 48.7 ± 11.9 μm dimaprit was required to produce 50% inhibition of the twitch response in tissues from IS mice. In addition, the agonist actions of dimaprit were incomplete in the latter tissues, the drug eliciting no more than 75% inhibition of the twitch response at concentrations in the range 300−1000 μm. Tiotidine produced competitive antagonism of the actions of both histamine and dimaprit, the strain differences being of the same magnitude as those observed for cimetidine.
Mating of a representative S (SWR) and IS (129/Sv) strain produced F1 mice with intermediate histamine and cimetidine sensitivities relative to the parental strains. A backcross of male F1 to female IS mice produced progeny displaying a range of histamine and cimetidine sensitivities representative of those seen in tissues from F1 and IS parental animals, however, the data were not bimodal. Thus, the backcross data provided no evidence to support single gene inheritance of histamine sensitivity and might suggest that more than one gene is responsible for these differences between S and IS mice.
Release of endogenous dopamine from rat isolated striatum: effect of clorgyline and (−)−deprenyl
Authors: Hársing L.G. , Vizi E.S. 
Published: July 2012

High performance liquid chromatography with electrochemical detection was used to measure the release and content of dopamine and dihydroxyphenylacetic acid (DOPAC) from rat isolated striatum. The effects of the monoamine oxidase (MAO) inhibitors clorgyline and (−)−deprenyl on dopamine and DOPAC release and contents, and the IC50 values of these compounds for inhibition of dopamine deamination in rat striatum were determined.
Dopamine release was significantly increased by elevated KCl (22 mm) in a Ca2+‐dependent manner, and by ouabain (20 μm), whereas the release of DOPAC remained constant. The loss in striatal dopamine content during the incubation period (67% of initial content) was far greater than the amount of dopamine recovered in the incubation fluid (16% of initial content), suggesting that much of the DOPAC, released during incubation originated from the conversion of dopamine to DOPAC within the striatum.
A concentration‐dependent decrease in DOPAC efflux, both during rest and stimulation periods, was observed in the presence of clorgyline (10−8m‐10−7m) and (−)−deprenyl (10−5m‐10−4m).
Higher concentrations of clorgyline (10−7m) and (−)−deprenyl (10−4m), which inhibited dopamine deamination by 85–90%, enhanced both the resting and KCl‐induced release of dopamine.
The total amount of dopamine plus DOPAC that was released in the presence of clorgyline or (−)−deprenyl did not differ from control values, suggesting that the increase in dopamine release elicited by MAO inhibitors might result from reduced degradation of dopamine to DOPAC.
The IC50 values of clorgyline (5 × 10−9m) and (−)−deprenyl (5 × 10−6m) for inhibition of dopamine deamination indicate that dopamine is a substrate for type A MAO in rat striatum.
Comparison of the biphasic excitatory junction potential with membrane responses to adenosine triphosphate and noradrenaline in the rat anococcygeus muscle
Authors: Byrne N.G. , Large W. A. 
Published: July 2012

The effects of field stimulation and ionophoretic application of adenosine triphosphate (ATP) and noradrenaline were studied in the rat anococcygeus by means of an intracellular micro‐electrode.
Field stimulation at room temperature produced three types of electrical membrane response: (a) a ‘fast’ excitatory junction potential (e.j.p.) which had a latency of less than 100 ms and a time to peak of 300 ms; (b) a ‘slow’ e.j.p. which had a latency of several hundred ms and a time to peak of 1–2 s, and (c) an inhibitory junction potential (i.j.p.) which had a time to peak of about 1.5 s. All three responses were blocked by tetrodotoxin.
The ionophoretic application of ATP produced both monophasic and biphasic depolarizations; these responses had a latency of less than 30 ms and a time to peak of 150–300 ms. In contrast, ionophoretically‐applied noradrenaline produced a depolarization which had a mean latency of 471 ms and a time to peak of 861 ms.
The ‘slow’ e.j.p. and the noradrenaline‐induced depolarization were blocked by prazosin whereas the ‘fast’ e.j.p. and the ATP responses were resistant to this antagonist and also to atropine.
These results are further evidence that the ‘fast’ e.j.p. in some smooth muscle tissues is mediated by ATP.
Reduction by phentolamine of the hypotensive effect of methionine enkephalin in anaesthetized rabbits
Authors: Eulie P.J. , Rhee H.M. 
Published: July 2012

In intact rabbits anaesthetized with pentobarbitone, methionine enkephalin (Met enkephalin, 1−1,000 μg kg−1 i.v.) produced a dose‐dependent bradycardia and hypotension.
The bradycardia and hypotension were antagonized by naloxone hydrochloride (1 mg kg−1), but not by naloxone methobromide (1.3 mg kg−1).
Phentolamine (1 and 4 mg kg−1 i.v.) blocked both the hypotension and bradycardia produced by Met enkephalin.
The inhibitory effect of phentolamine was not due to a simple hypotensive action of this drug per se because a similar degree of hypotension induced by nitroprusside (15 μg kg−1, i.v.) caused a further reduction of pressure when Met enkephalin was added.
Atropine (2 mg kg−1) reduced the bradycardia but not the hypotensive response to Met enkephalin.
Met enkephalin did not antagonize the vasopressor effect of exogenous noradrenaline (2–8 μg kg−1, i.v.).
Met enkephalin had no significant effects in superfused thoracic aortic strips and in isolated perfused hearts of rabbits.
It is concluded that the cardiovascular effects of Met enkephalin are more probably due to an action on the central nervous system, although a peripheral site of action cannot be completely excluded.
A comparison of analgesia and suppression of oxytocin release by opiates
Authors: Clarke G. , Wright D.M. 
Published: July 2012

The potency of opiates for suppressing oxytocin release relative to their potency as analgesics was tested in lactating rats.
Oxytoxin release was evoked by the sucking of the young in urethane‐anaesthetized and unanaesthetized rats, and was detected by the characteristic behaviour of the young and milk yield respectively.
The tail‐flick test, using noxious radiant heat, was used to assess analgesia.
Intraperitoneal injection of morphine (1 mg kg−1 and 5 mg kg−1) significantly reduced milk yield in unanaesthetized rats.
Urethane‐anaesthetized rats displayed a pattern of reflex milk‐ejection responses similar to that found in conscious rats. This reflex was significantly inhibited in a dose‐related, naloxone‐reversible manner by buprenorphine (ED50 0.18 mg kg−1), meptazinol (ED50: 14.0 mg kg−1), morphine (ED50: 0.67 mg kg−1), pentazocine (ED50: 15.0 mg kg−1) and pethidine (ED50: 7.9 mg kg−1).
Although intraperitoneal injection of morphine (5 mg kg−1) abolished the increase in intramammary pressure occurring at reflex milk‐ejection, that evoked by intravenous oxytocin (0.5−1 mu) was unaffected.
Each opiate also caused significant, dose‐related, naloxone‐reversible increases in tail‐flick latency. The ED50 doses were buprenorphine (ED50: 0.14 mg kg−1), meptazinol (ED50: 12.5 mg kg−1), morphine (ED50: 5.0 mg kg−1), pentazocine (ED50: 12.5 mg kg−1) and pethidine (ED50: 6.1 mg kg−1).
The order of potency for analgesia and for suppression of oxytocin release were identical, namely: buprenorphine > morphine > pethidine > meptazinol > pentazocine.
The results obtained with lactating rats suggest that secretion of the hormone oxytocin is substantially reduced during opiate‐induced analgesia.
Efflux of 86Rb from rat and mouse pancreatic islets: the role of membrane depolarization
Authors: Matthews E.K. , Shotton P.A. 
Published: July 2012

The efflux of 86Rb from rat or mouse perifused islets preloaded with the isotope has been used as an index of the potassium permeability of the islet β‐cell membrane. Cellular transmembrane potentials were altered by changing [K]o or by direct electrical stimulation and the effects on potassium permeability examined.
Omission of KCl from the medium perif using rat islets induced a biphasic change in 86Rb efflux, a brief decline being superseded by a pronounced increase in efflux. Re‐introduction of KCl, 4.7 mm, caused a further increase in 86Rb efflux preceding a return to control values.
Increasing [K]o from 4.7 mm to 10 mm, 20 mm or 47 mm caused a phasic increase in 86Rb efflux with the magnitude of both the peak and average rate of efflux being dependent upon the extent of the change in [K]o.
The increase in 86Rb efflux produced by [K]o, 47 mm, was attenuated by Co2+, 2.56 mm (51% inhibition) or quinine, 10 μm (47% inhibition), but efflux remained significantly (P<0.001) above control values.
Electrical stimulation of single microdissected mouse pancreatic islets by currents of 0.1 to 0.5 mA evoked a rapid, phasic increase in 86Rb efflux. The magnitude of the response was unaffected by EGTA, 2 mm, or nupercaine, 100 μm.
These observations are discussed in relation to the mechanisms controlling the potassium permeability, membrane potential and insulin secretion of the pancreatic islet β‐cell. It is concluded that β‐cell depolarization by a raised [K]o increases potassium permeability and efflux by at least two mechanisms: (i) a calcium‐dependent potassium efflux triggered by an increase in [Ca]i and (ii) an activation of voltage‐sensitive potassium channels which occurs even when the calcium‐dependent potassium permeability is blocked.
Differential effects of D600, nifedipine and dantrolene sodium on excitation‐secretion coupling and presynaptic β‐adrenoceptor responses in rat atria
Authors: Callanan K.M. , Keenan A.K. 
Published: July 2012

The stimulation‐evoked release of tritium was measured from rat atria labelled with [3H]‐noradrenaline. The calcium dependence of evoked release and the facilitation of this release via activation of presynaptic β‐adrenoceptors were examined using D600 (methoxyverapamil), nifedipine and dantrolene sodium.
Both D600 and nifedipine at dose levels of 20 and 100 μm inhibited evoked release. Dantrolene (20, 100 μm) reduced release by 25%, the effect being maximal at 20 μLm.
In the presence of 20 nm isoprenaline, a facilitation of evoked release occurred, which was blocked by 0.1 μm (—)‐propranolol.
The facilitatory action of isoprenaline was abolished by omission of calcium from the buffer, or by D600 or nifedipine, (100 μm). In contrast, the response to isoprenaline was not modified by dantrolene (20, 100 μm).
It is concluded that (a) the evoked release of noradrenaline (NA) utilizes Ca from both intra‐ and extracellular sources and that (b) isoprenaline increases NA secretion by promoting the depolarization‐induced influx of Ca.
Hydrodynamic properties of muscarinic acetylcholine receptors solubilized from rat forebrain
Authors: Berrie Christopher P. , Birdsall Nigel J.M. , Haga Kazuko , Haga Tatsuya , Hulme Edward C. 
Published: July 2012

Muscarinic receptors from rat forebrain have been solubilized by Lubrol PX, lysophosphatidyl‐choline (LPC), digitonin and cholate/1 M sodium chloride. The overall level of solubilization was characterized using receptors prelabelled with an irreversible antagonist. The recovery of non‐denatured soluble binding activity was estimated using reversible tritiated antagonists.
All these detergents solubilized 60–85% of the total binding sites. In Lubrol PX most of the receptors were recovered in a denatured form. In the other detergents 30–90% of the solubilized receptors were stable and capable of binding reversible [3H]‐antagonists with high affinity.
The hydrodynamic properties of the soluble receptors have been examined by gel filtration and sucrose gradient centrifugation in H2O and D2O.
The soluble receptors in Lubrol PX, lysophosphatidylcholine and cholate were, in general, heterogeneous as regards their molecular size. Estimates of the molecular weight after correction for bound detergent, varied from 82,000 to 134, 000. Conditions were identified under which the receptor was largely monodisperse, and the estimates of molecular weight agreed with values (ca. 83, 000) from sodium dodecylsulphate (SDS) Polyacrylamide gel electrophoresis. The amount of bound detergent could not be calculated for the digitonin‐muscarinic receptor complex which had an estimated overall median molecular weight of about 290,000.
It is concluded that a subpopulation of muscarinic receptors from the rat forebrain is capable of existing in a monomelic soluble form and binding ligands. There is also evidence that complexes with other proteins can exist, but their specificity and functional relevance are not known.
Effects of p‐chlorophenylalanine on the sensitivity of rat intestine to agonists and on intestinal 5‐hydroxytryptamine levels during Nippostrongylus brasiliensis infection
Authors: Farmer Stephen G. , Laniyonu Adebayo A. 
Published: July 2012

Infection of rats with the nematode N. brasiliensis caused non‐specific increases in maximum response of isolated intestine to acetylcholine and 5‐hydroxytryptamine (5‐HT), and a specific subsensitivity to 5‐HT.
Intestinal levels of 5‐HT, measured fluorimetrically, increased approximately 2 fold during infection.
Treatment of infected rats with parachlorophenylalanine (PCPA) depleted the gut of 5‐HT, and prevented the specific subsensitivity to the amine but not the increases in maximum response.
Depletion of intestinal 5‐HT did not prevent the immune expulsion of the parasites.
It is concluded that the specific subsensitivity of the gut is due to the elevated levels of 5‐HT during infection, but that the increased maximum responses are due to some other factor. Further, the lack of effect of PCPA on parasite rejection casts doubt on the proposed role of 5‐HT in this process.
Location of [125I]‐angiotensin II receptors on rat kidney cortex epithelial cells
Authors: Cox Helen M. , Munday Kenneth A. , Poat Judith A. 
Published: July 2012

Angiotensin II (AII) stimulates active Na+ extrusion from Na+ loaded renal cortex slices.
Specific high affinity [125I]‐AII binding sites in partially purified basolateral and brush‐border epithelial membranes exhibit a KD of 0.88 nM and Bmax of 321.13 fmol mg−1 protein.
Separation and purification of brush‐border membranes yielded high affinity [125I]‐AII binding sites with KD of 1.02 nM and Bmax of 56.6 fmol mg−1 protein.
Angiotensin II receptors of the same affinity are present on renal cortex brush‐border and basolateral membranes but a greater proportion are located on the latter. These receptors may be involved in the direct control of Na+ and water transport by AII.