bluuebunny/crossref_metadata_2025_split huggingface dataset:
The contribution of α‐adrenoceptors to neurally‐mediated contractions of the rabbit urethral smooth muscle
Authors: Chen Hong‐I , Brading Alison F. 
Published: July 2012

The nature of the nerve‐mediated contractions in the urethral smooth muscle from the rabbit was studied in vitro. Field stimulation caused smaller contractile responses than in the detrusor of the rabbit.
There was no significant difference in response to field stimulation or exogenous agents acting on adrenoceptors between longitudinal and circular strips from the rabbit urethra. Histological studies showed that the urethral muscle is arranged in three layers, which run circularly and longitudinally.
Atropine had very little effect on the response to field stimulation, phentolamine almost abolished the contractile response to nerve stimulation and sometimes unmasked a relaxation.
The α1‐adrenoceptor blocking agent, prazosin, blocked both the contractile response to the α1‐receptor agonist phenylephrine and that to intrinsic nerve stimulation, with similar potencies. The α2‐blocking agent yohimbine shifted the dose‐response curve of the contractile response to the α2‐agonist, clonidine, in a dose‐dependent manner, 10−7 m causing a 10 fold shift. This concentration had no effect on the response to intrinsic nerve stimulation, suggesting that α2‐receptors are not involved in the response. Higher concentrations of yohimbine caused a suppression of the nerve‐evoked response which is assumed to be non‐specific.
Noradrenaline, phenylephrine, and clonidine caused dose‐dependent contractile responses in the rabbit urethral strips. The contractions induced by clonidine developed more slowly than those induced by noradrenaline and phenylephrine.
These results demonstrate that the rabbit urethral smooth muscle contains both α1‐ and α2‐adrenoceptors, and the nerve‐mediated contraction of the rabbit urethra is adrenergic in nature and mediated mainly via α1‐adrenoceptors.
Cholinoceptor regulation of cyclic AMP levels in bovine adrenal medullary cells
Authors: Anderson Karen , Robinson Phillip J. , Marley Philip D. 
Published: July 2012

The regulation of adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) levels by cholinoceptors has been studied in cultured bovine adrenal medullary cells.
Acetylcholine (100 μm), nicotine (10 μm) and dimethylphenylpiperazinium (20 μm) each increased cellular cyclic AMP levels 2 to 4 fold over 5 min in the absence of phosphodiesterase inhibitors. The muscarinic agonist acetyl‐β‐methylcholine (100 μm) had no effect either on its own or on the response to nicotine. The responses to acetylcholine and nicotine were unaffected by atropine (1 μm) but were abolished by mecamylamine (5 μm).
Cellular cyclic AMP increased transiently during continuous exposure to nicotine (1–20 μm), with the largest response seen after 5 min, a smaller response after 20 min, and no change in cyclic AMP levels seen after 90 or 180 min. The maximal response after 5 min stimulation was seen with 5‐ 10 μm nicotine and the EC50 was about 2 μm. In contrast, extracellular cyclic AMP levels did not change after 5 or 20 min stimulation with nicotine, but increased slightly after 90 min and further after 180 min.
The cellular cyclic AMP response to nicotine (10 μm) was unchanged or weakly enhanced in the presence of the unselective phosphodiesterase inhibitor, isobutylmethylxanthine, and was unchanged in the presence of rolipram. Nicotine did not interact synergistically with low concentrations of forskolin. The response was however completely abolished in the absence of extracellular Ca2+.
The nicotinic cyclic AMP response was almost abolished by sphingosine (30 μm), which did not inhibit the cyclic AMP response to phorbol‐12,13‐dibutyrate (PDB). The nicotinic response was reduced by 55% by the calmodulin antagonist W7 at 3 μm, and by >90% at 10 μm W7. At these concentrations, W7 had no effect on the cyclic AMP response to 100 nm PDB. The nicotinic response was also selectively abolished by another calmodulin antagonist, trifluoperazine (10 μm).
The results indicate that nicotinic cholinoceptors can increase cyclic AMP production in chromaffin cells by a mechanism that does not directly involve Gs, that is dependent on extracellular Ca2+ and that is sensitive to the calmodulin antagonists W7 and trifluoperazine. We propose that a Ca2+/calmodulin‐sensitive adenylate cyclase may mediate the nicotinic cyclic AMP response in bovine chromaffin cells.
Effect of lignocaine on arginine‐vasopressin plasma levels: baseline or induced by frusemide
Authors: Gariépy Louise , Larose Patrice , Bailey Benoit , du Souich Patrick 
Published: July 2012

To assess whether or not lignocaine influences baseline and frusemide‐induced (5 mg kg−1) plasma concentrations of arginine‐vasopressin (AVP), 2 groups of rabbits received an infusion of lignocaine (130 μg min−1 kg−1) for 6 h. Lignocaine‐induced changes in AVP plasma concentrations were substantiated by measurement of diuresis and natriuresis and hepatic plasma flow, by means of an infusion of indocyanine green (ICG) (249 μg min−1 kg−1).
Baseline plasma AVP levels were 4.9 ± 0.9 pg ml−1 (± s.e.), and following lignocaine, these values were reduced to 0.7 ± 0.1 pg ml−1 (P < 0.01). Frusemide increased AVP levels to 134.1 ± 73.6 pg ml−1 (P < 0.05) and lignocaine totally prevented this increase, e.g. mean AVP levels of 2.7 pg ml−1.
Lignocaine enhanced baseline diuresis secondary to an increase in free water clearance; none of the experimental conditions affected the diuresis and natriuresis induced by frusemide.
Frusemide reduced the hepatic plasma flow and this decrease was not reversed by the infusion of lignocaine.
It is concluded that in healthy rabbits lignocaine reduces baseline secretion of AVP and its antidiuretic effect; in addition, lignocaine prevents the rise in AVP induced by frusemide.
Effect of the β‐adrenoceptor agonist clenbuterol and phytohaemagglutinin on growth, protein synthesis and polyamine metabolism of tissues of the rat
Authors: Bardocz S. , Brown D.S. , Grant G. , Pusztai A. , Stewart J.C. , Palmer R.M. 
Published: July 2012

The kidney bean lectin, phytohaemagglutinin (PHA), induced a marked atrophy of skeletal muscle which was evident from the changes in tissue composition (protein, RNA, DNA and polyamine content) and from the reduction in weight and protein synthesis of hind leg muscles of rats fed on kidney bean‐diets for four days. The β‐adrenoceptor agonist, clenbuterol, induced skeletal muscle hypertrophy by transiently stimulating protein synthesis. As a consequence, the muscle loss caused by a short exposure to PHA was, in part, ameliorated by clenbuterol treatment.
Cardiac muscle was affected to a lesser extent than skeletal muscle by both clenbuterol and the lectin. However, there was evidence that protein synthesis in heart was reduced by PHA.
PHA had opposite effects on the gut, the lectin‐induced hyperplasia of the jejunum was accompanied by a large increase in protein synthesis. Clenbuterol alone had no effect on the jejunum whereas a combination of PHA and clenbuterol appeared to exacerbate the effect of the lectin on gut.
Both the lectin‐induced gut growth and the hypertrophy of skeletal muscle caused by clenbuterol were preceded by the accumulation of polyamines in the respective tissues. Of particular note was the observation that a significant increase in the proportion of the intraperitoneally injected 14C‐labelled spermidine or putrescine taken up by the growing tissues could be detected by the second day. Therefore, the measurement of uptake of labelled polyamines may be used as a sensitive indicator of early alterations in tissue metabolism.
Pathological events in experimental acute pancreatitis prevented by the bradykinin antagonist, Hoe 140
Authors: Griesbacher Thomas , Tiran Beate , Lembeck Fred 
Published: July 2012

In a previous investigation, Hoe 140, a specific and potent bradykinin B2 receptor antagonist, prevented the pancreatic oedema and the hypotension observed during acute experimental pancreatitis; however, it augmented the associated rises in the serum activities of pancreatic enzymes. Therefore, we have now investigated the consequences of the pancreatic oedema for the fate of activated enzymes released into the tissue during the course of acute pancreatitis.
Acute oedematous pancreatitis was induced in rats, pretreated with captopril (50 μmol kg−1, i.p.), by hyperstimulation of the exocrine function of the pancreas with the cholecystokinin analogue, caerulein (4 nmol kg−1 h−1, i.v.), for up to 120 min.
Pancreatic oedema began to develop 10 min after the start of the caerulein infusion, reached a maximum within about 45 min, and then declined slightly. The development of the oedema parallelled the second phase of the caerulein‐induced fall in blood pressure found in earlier experiments. No further extravasation of plasma proteins occurred during the 2nd hour of the caerulein infusion. The oedema formation was completely blocked in animals pretreated with the bradykinin receptor antagonist, Hoe 140 (100 nmol kg−1, s.c.). Pretreatment with aprotinin or soy bean trypsin inhibitor did not result in a significant inhibition of the oedema.
The haematocrit of animals with experimental pancreatitis showed a pronounced increase which started 10 min after the start of the caerulein infusion and reached maximal values at 60 min. The changes in haematocrit showed a reduction in total blood volume of 28% due to a 48% loss of plasma. This effect was completely blocked by Hoe 140.
In rats with caerulein‐induced pancreatitis, there was a time‐dependent increase in the activities of amylase and lipase in blood serum as well as in the pancreas. Pretreatment with Hoe 140 greatly augmented the caerulein‐induced rise in enzyme activities in blood serum but potently attenuated it in the pancreas. The activities of trypsin in both the blood serum and the pancreas were below or near the limit of detection in all experimental groups.
It is concluded that the second phase of hypotension in this model of acute pancreatitis is due to the liberation of kinins which cause a massive loss of blood plasma into the pancreas and into the retroperitoneal space. Activated enzymes are trapped in the pancreas, at least in part, by the oedema of the gland. Treatment with Hoe 140 prevents the oedema formation and greatly facilitates the egress of activated enzymes from the pancreas.
Actions of agonists of metabotropic glutamate receptors on synaptic transmission and transmitter release in the olfactory cortex
Authors: Collins G.G.S. 
Published: July 2012

The effects of agonists of metabotropic glutamate receptors on the evoked N‐wave complex in slices of mouse olfactory cortex have been studied: most experiments were carried out using slices perfused with Mg2+‐free solution to which 10 μm of either 6,7‐dinitroquinoxaline‐2,3‐dione or 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione was applied.
Following agonist washout, a slowly developing, long lasting potentiation of the complex occurred which was confined to the N‐methyl‐d‐aspartate (NMDA) receptor‐mediated component of the potential. The relative agonist potencies were 1S,3R‐1‐aminocyclopentane‐1,3‐dicarboxylic acid (1S,3R‐ACPD, 5–250 μm) = quisqualate (5–50 μm) > 1RS,3RS‐cis‐1‐aminocyclopentane‐1,3‐dicarboxylic acid (ACPD, 25–1000 μm) > l‐glutamate (0.25–2.5 mm); NMDA, α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole‐propionate (AMPA) and l‐aspartate were inactive.
Potentiation of the NMDA receptor‐mediated component by 1S,3R‐ACPD (0.1 mm) was non‐competitively antagonised by S‐(+)‐ but not R‐(−)‐2‐amino‐3‐phosphonopropionate (AP3, 0.125 mm), equally by d‐(−) and l‐(+)‐2‐amino‐4‐phosphonobutyrate (0.25 mm) and also by the protein kinase C inhibitors sphingosine, (25 μm), sangivamycin (25 μm) and 5‐(isoquinolinylsulphonyl)‐3‐methylpiperazine (50 μm).
In a series of input‐output experiments, 1S,3R‐ACPD (0.1 mm) reversibly reduced the latency to peak of the NMDA receptor‐mediated component at submaximal stimulus intensities, an effect blocked by S‐(+)‐AP3 (0.125 mm). On agonist washout, there was an increase in the area of the NMDA receptor‐mediated component over all stimulus intensities, an effect blocked by the inhibitors of protein kinase C and by S‐(+)‐AP3 (0.125 mm). 4‐β‐Phorbol‐12,13‐diacetate (2.5 μm) also potentiated the component, an action inhibited by protein kinase C inhibitors but not by S‐(+)‐AP3.
1S,3R‐ACPD (0.1 mm) had no significant effect on postsynaptic responses evoked by NMDA, AMPA and kainate, but significantly reversed a partial antagonism of NMDA responses produced by 7‐chlorokynurenate (2.5 μm).
The K+‐evoked release of glycine was selectively and significantly increased in the presence of 0.1 mm 1S,3R‐ACPD (antagonized by 0.125 mm S‐(+)‐AP3) whereas following agonist washout, release of glycine fell to control levels but there was a significant increase in release of aspartate (antagonized by 25 μm sangivamycin and 0.125 mm S‐(+)‐AP3).
It is concluded that metabotropic glutamate receptors mediate (i) a reduction in the latency of the NMDA receptor‐mediated component of potentials by a mechanism that is independent of protein kinase C but which may depend on increased glycine release and (ii) a long lasting increase in the total area of the potential by increasing transmitter (possibly aspartate) release by a mechanism that is protein kinase C‐dependent.
Effects of capsaicin and 5‐HT3 antagonists on 5‐hydroxytryptamine‐evoked release of calcitonin gene‐related peptide in the guinea‐pig heart
Authors: Tramontana Manuela , Giuliani Sandro , Del Bianco Elena , Lecci Alessandro , Maggi Carlo A. , Evangelista Stefano , Geppetti Pierangelo 
Published: July 2012

The effect of 5‐hydroxytryptamine (5‐HT) on the release of calcitonin gene‐related peptide (CGRP) was studied directly in the isolated perfused heart and indirectly in the isolated left atria of guinea‐pig.
5‐HT injection into the guinea‐pig isolated and perfused heart evoked a dose‐dependent (1–100 μm) release of CGRP‐like immunoreactivity (LI) that was abolished by in vitro pretreatment with capsaicin and was not affected by indomethacin.
Chlorophenyldiguanide (CPD, 100 μm), but not 8‐hydroxy‐dipropylaminotetralin (8‐OH‐DPAT, 100 μm), sumatriptan (100 μm) or 1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane (DOI, 100 μm) evoked a release of CGRP‐LI. Ondansetron (10 μm) or ICS205‐930 (20 μm) completely abolished the 5‐HT (100 μm)‐evoked CGRP‐LI release.
In the isolated electrically driven left atria of the guinea‐pig 5‐HT (1–10 μm) and CPD (3–100 μm) produced a positive inotropic response, which was abolished by capsaicin pretreatment. 8‐OH‐DPAT (10 μm) and DOI (10 μm) were inactive. Ondansetron inhibited the response to 5‐HT with a pA2 of 6.50 (CL 6.08–6.91).
It is concluded that 5‐HT causes a release of CGRP in the whole heart and a positive inotropic response in the isolated atria of guinea‐pig. Both these effects are sensitive to capsaicin pretreatment and to 5‐HT3 antagonists.
In vitro characterization of prostanoid receptors on human myometrium at term pregnancy
Authors: Senior J. , Marshall K. , Sangha R. , Clayton J.K. 
Published: July 2012

Prostanoid receptors present on the pregnant human myometrium in vitro have been characterized according to the receptor classification proposed by Coleman et al. (1984) using natural prostanoids and synthetic, selective analogues and antagonists where available.
Prostaglandin E2 (PGE2) produced a biphasic effect consisting of an initial excitation followed by a dose‐related inhibition. The EP2/EP3‐receptor agonists, rioprostil and misoprostol, produced similar effects to PGE2, however, the excitatory event of the misoprostol response was related to dose. The EP1/EP3‐receptor agonist, sulprostone, evoked a purely excitatory response which was unaffected by AH6809. The selective EP2‐receptor agonist butaprost produced a long‐lasting dose‐dependent inhibition of activity. The results from these prostanoids indicated that inhibitory EP2‐ and excitatory EP3‐receptors are present on myometrium from pregnant donors at term.
PGF2α and the synthetic FP‐receptor agonist, fluprostenol, caused equipotent excitatory effects, indicating the presence of contractile FP‐receptors.
PGD2 produced a biphasic effect of which the inhibition appeared dose‐related and was antagonized by the selective DP‐receptor antagonist BW A868C. The selective DP‐receptor agonist, BW245C, produced a potent inhibitory effect that was competitively antagonized by BW A868C (pA2 = 8.6).
PGI2 produced a biphasic response qualitatively similar to PGE2. The EP1/IP‐receptor agonist, iloprost, produced an occasional unquantifiable excitation and dose‐related inhibition. The selective IP‐receptor prostanoid, cicaprost, evoked only an inhibitory response.
The stable thromboxane A2 (TXA2)‐mimetic, U46619, produced potent excitation which was competitively antagonized by the TP‐receptor antagonist, GR32191 (pA2 = 7.2).
The prostanoids tested indicate that a heterogeneous population of prostanoid receptors are present on human myometrium from pregnant donors. It may be concluded that excitation is EP3‐, FP‐ and TP‐receptor‐mediated and inhibition is EP2‐, DP‐ and IP‐receptor‐mediated. Comparison of data obtained from non‐pregnant specimens indicates that the lower segment tissue from pregnant donors demonstrated more pronounced responses to EP2 and IP‐receptor activation.
Investigations into factors determining the duration of action of the β2‐adrenoceptor agonist, salmeterol
Authors: Nials Anthony T. , Sumner Michael J. , Johnson Malcolm , Coleman Robert A. 
Published: July 2012

This study has explored the mechanism underlying the long duration of action of the β2‐adrenoceptor agonist, salmeterol.
Salmeterol, salbutamol and isoprenaline caused a concentration‐related inhibition of electrically‐induced contractile responses of the guinea‐pig superfused trachea preparation. The effects of both isoprenaline and salbutamol were rapid in onset and rapidly reversed upon removal of the agonist. In contrast, the effects of salmeterol were slower in onset and could not be reversed by superfusion of the tissue with agonist‐free Krebs solution even for periods of up to 10 h.
The effects of salmeterol were, however, readily reversed by a number of β‐adrenoceptor blocking drugs, as was the effect of a continuous infusion of isoprenaline. Upon removal of the antagonist, however, the effects of salmeterol and of the isoprenaline infusion were reasserted at a rate which was inversely related to the lipophilicity of a β‐adrenoceptor blocking drugs.
Salmeterol inhibited the binding of [125I]‐(−)‐iodopindolol (100 pm) to rat lung membranes (pIC50 7.1), with isoprenaline (pIC506.2) and salbutamol (pIC50 5.1) having lower potencies. The inhibition of binding by salmeterol was apparently non‐competitive, whereas that produced by salbutamol and isoprenaline was competitive in nature.
Isoprenaline and salbutamol rapidly dissociated from their binding sites, whereas in marked contrast, the binding of salmeterol showed no dissociation for periods of up to 1 h.
These data are consistent with a mechanism in which salmeterol binds adjacent to the active site of the β2‐adrenoceptor, such that the drug cannot be washed out of the tissue, yet can interact with and activate the receptor. This latter property is susceptible to antagonism by β‐adrenoceptor blocking drugs but is reasserted when the antagonists are removed.
Investigation into the role of phosphodiesterase IV in bronchorelaxation, including studies with human bronchus
Authors: Cortijo J. , Bou J. , Beleta J. , Cardelús I. , Llenas J. , Morcillo E. , Gristwood R.W. 
Published: July 2012

We have investigated the role of cyclic nucleotide phosphodiesterase IV (PDEIV) in the relaxation of human bronchus and guinea‐pig trachea in vitro and in guinea‐pigs in vivo.
Functional studies showed that the selective PDE IV inhibitors, rolipram and denbufylline, relaxed human and guinea‐pig preparations in vitro.
Two clinically used xanthine non‐selective PDE inhibitors, theophylline and pentoxifylline, were also effective in these preparations, but were much less potent than the selective agents used.
The rank order of potency for the four PDE inhibitors in both species was similar.
Biochemical studies indicated that PDE IV was the major PDE isoform present in the human bronchial tissue. PDEs I, II and V were also identified.
Theophylline and pentoxifylline were, as expected, non‐selective inhibitors of the human enzymes, but there was a good correlation between PDE IV inhibitory and bronchorelaxation potencies, suggesting that PDE IV inhibition is important for the clinical bronchodilator activities of the two xanthine compounds.
We have confirmed the ability of selective PDE IV inhibitors to cause bronchodilatation in guinea‐pigs in vivo.
We conclude that our study has provided further evidence that selective PDE IV inhibitors could act as bronchodilators in the clinic.
Ca2+‐dependent aggregation of rabbit platelets induced by maitotoxin, a potent marine toxin, isolated from a dinoflagellate
Authors: Watanabe Akiko , Ishida Yukisato , Honda Hiromi , Kobayashi Masaki , Ohizumi Yasushi 
Published: July 2012

Administration of maitotoxin (MTX), a dinoflagellate toxin, caused aggregation of rabbit washed platelets. The cytosolic Ca2+ concentration ([Ca2+]i), measured by fura‐2 fluorescence technique, was also increased by the presence of MTX. Rates of aggregation response and [Ca2+]i‐increase were dependent on tested concentrations (3–100 ng ml−1) of the toxin.
The MTX‐induced platelet aggregation and [Ca2+]i‐increase were totally abolished in a Ca2+‐free solution. The successive administration of Ca2+ in the presence of MTX elicited the aggregation and increase in [Ca2+]i.
Ba2+ was capable of substituting for Ca2+ in the MTX‐induced platelet aggregation. In the presence of external Ca2+, transition metals, Co2+, Cd2+ and Ni2+, inhibited the aggregation response to MTX.
Organic calcium antagonists (verapamil and nifedipine) as well as a cyclo‐oxygenase‐inhibitor (aspirin) did not apparently inhibit the aggregation response to MTX, except for a high concentration (10−5 m) of verapamil, while procaine (10 mm) reduced the rate of platelet aggregation.
MTX also elicited a release of ATP from platelets, which was abolished in the absence of external Ca2+.
In contrast, thrombin 0.5 unit ml−1 could elicit platelet shape change, [Ca2+]i‐increase and ATP‐release in the absence of external Ca2+.
These results suggest that the MTX‐induced platelet activation is caused by an enhanced Ca2+‐influx presumably through voltage‐independent Ca2+ channels on the plasma membrane.