bluuebunny/crossref_metadata_2025_split huggingface dataset:
PULMONARY INACTIVATION OF 5‐HYDROXYTRYPTAMINE IS DECREASED DURING CIGARETTE SMOKE VENTILATION OF RAT ISOLATED LUNGS
Authors: KARHI TAINA , RANTALA ARTO , TOIVONEN HANNU 
Published: July 2012

The effect of cigarette smoke ventilation on the inactivation of [14C]‐5‐hydroxytryptamine (5‐HT) was studied in isolated perfused lungs of the rat.
[14C]‐5‐HT 9.6 nmol was infused into the pulmonary circulation of rat lungs in 3 min. The nonrecirculating perfusion effluent was collected during the 5‐HT infusion in three consecutive 1 min fractions. The amount of metabolites of 5‐HT was determined from the perfusion effluent and from the perfused lungs.
The amount of metabolites of 5‐HT in the perfusion effluent was decreased during cigarette smoke ventilation.
The amount of metabolites of 5‐HT in the perfused lungs was also decreased by cigarette smoke ventilation, although the total amount of radioactivity in the lung tissue was not significantly changed.
The decreased pulmonary inactivation of 5‐HT may cause increased circulating levels of 5‐HT, which would explain some cardiovascular changes during smoking.
ELECTROPHYSIOLOGICAL EFFECTS OF THE SALICYLATES ON ISOLATED ATRIAL MUSCLE OF THE RABBIT
Authors: NETO FRANCISCO RICCIOPPO 
Published: July 2012

Intracellular recordings were made from cells of the sinoatrial (S‐A) node region and from atrial muscle fibres of rabbit hearts. The effects of sodium salicylate and 5‐bromo salicylate on various parameters of the membrane action potential were studied.
5‐Bromo salicylate (30–100 μm) and sodium salicylate (300–500 μm) caused a dose‐dependent decrease in the frequency of discharge of the SA node cells. Applications of atropine (2.6 μm) with propranolol (3.3 μm) did not affect the negative chronotropic effect, whereas adrenaline (5 μm) reversed it.
Depolarization and shortening of the action potential duration were found in atrial muscle fibres after the application of 5‐bromo salicylate (60–100 μm). The reduction of the action potential duration (APD) was not affected by atropine (2.6 μm).
Higher concentrations of 5‐bromo salicylate (> 100 μm) also caused a dose‐dependent reduction in the action potential amplitude (APA), in the overshoot (OS) of the action potential and in the maximum rate of rise of the action potential (Vmax). All these effects were completely reversed on washing.
Substitution of the NaCl of the bathing Tyrode solution by an equimolar concentration of Na isethionate did not affect the plateau depression induced by the salicylates in atrial muscle fibres.
After increasing the K concentration to 27 mm in the presence of isoprenaline (1 μm), ‘slow responses’ were obtained upon stimulation. 5‐Bromo salicylate (20–60 μm) and sodium salicylate (100 μm) decreased reversibly the amplitude and the rate of rise of the ‘slow response’.
A four fold increase in Ca concentration of the standard Tyrode solution did not antagonize the plateau depression of atrial muscle fibres or the negative chronotropism induced by salicylates.
Addition of CsCl (10 mm) to the Tyrode solution did not affect the shortening of the APD induced by the salicylates in atrial muscle fibres.
When the K concentration in the Tyrode solution was increased from 2.7 mm to 5.4 mm, the effects of 5‐bromo salicylate on the APA, OS and Vmax were potentiated. However, a significant reduction in the shortening of the APD produced by the salicylate was observed.
It is suggested that the salicylates possibly depress the slow inward current in both S‐A node cells and atrial muscle fibres of the rabbit heart. In atrial muscle fibres, a concomitant increase in the outward potassium current is probably involved.
DOPAMINE ACTS AT THE SAME RECEPTORS AS NORADRENALINE IN THE RAT ISOLATED VAS DEFERENS
Authors: LEEDHAM JUDITH A. , PENNEFATHER JOCELYN N. 
Published: July 2012

The proposal that dopamine activates a different population of receptors from those activated by noradrenaline and phenylephrine to cause contraction of the rat vas deferens has been investigated using a preparation of the epididymal half of this tissue.
In preparations preincubated in cocaine, oestradiol and propranolol, to block sites of amine loss and β‐adrenoceptors, noradrenaline was the most, and dopamine the least, potent of the three agonists. Phentolamine competitively inhibited each of the agonists to a similar extent. Prazosin also inhibited the actions of the three agonists to a similar extent. These results indicate that the three agonists activate a single population of α1‐adrenoceptors to cause contraction in this preparation.
In experiments using the prostatic half of the rat vas deferens, in the presence of cocaine, oestradiol, propranolol and prazosin, noradrenaline was approximately 40 times more potent than dopamine in causing inhibition of twitches induced by electrical field stimulation. Yohimbine competitively antagonized the effects of the two agonists to a similar extent indicating that both act at the same population of α2‐adrenoceptors.
Taken together, these findings do not lend support to proposals that there are populations of specific dopamine receptors located pre‐ and postjunctionally in the rat vas deferens.
COMPETITIVE INHIBITION BY ADENOSINE 5′‐TRIPHOSPHATE OF THE ACTIONS ON HUMAN PLATELETS OF 2‐CHLOROADENOSINE 5′‐DIPHOSPHATE, 2‐AZIDOADENOSINE 5′‐DIPHOSPHATE AND 2‐METHYLTHIOADENOSINE 5′‐DIPHOSPHATE
Authors: CUSACK N.J. , HOURANI S.M.O. 
Published: July 2012

Adenosine 5′‐diphosphate (ADP) induces human platelet aggregation and noncompetitively inhibits stimulated human platelet adenylate cyclase; these two effects are mediated by the same ADP receptor, at which adenosine 5′‐triphosphate (ATP) is a competitive antagonist.
Two ADP analogues, 2‐azidoadenosine 5′‐diphosphate (2‐azido‐ADP) and 2‐methylthioadenosine 5′‐diphosphate (2‐methylthio‐ADP) have been reported to be more potent as inhibitors of adenylate cyclase than they are as aggregating agents, but no evidence has been presented that these actions are mediated solely by the ADP receptor.
We therefore tested the ability of ATP to inhibit the actions of these compounds and of another ADP analogue, 2‐chloroadenosine 5′‐diphosphate (2‐chloro‐ADP).
2‐Chloro‐ADP, 2‐azido‐ADP and 2‐methylthio‐ADP each induced aggregation and inhibited stimulated adenylate cyclase. Both of these actions were competitively inhibited by ATP (50 μm) with pA2 values similar to those previously found for inhibition by ATP of these effects of ADP.
The reported greater potency of 2‐azido‐ADP and of 2‐methylthio‐ADP as inhibitors of adenylate cyclase than as aggregating agents is therefore due only to their greater efficacy for this effect, not to some extra actions elsewhere.
HISTAMINE H1‐AGONIST POTENTIATION OF ADENOSINE‐STIMULATED CYCLIC AMP ACCUMULATION IN SLICES OF GUINEA‐PIG CEREBRAL CORTEX: COMPARISON OF RESPONSE AND BINDING PARAMETERS
Authors: DAUM P.R. , HILL S.J. , YOUNG J.M. 
Published: July 2012

A range of histamine analogues have been examined as potentiators of the adenosine‐stimulated accumulation of cyclic adenosine 3′,5′‐monophosphate (cyclic AMP) in slices of guinea‐pig cerebral cortex. Dose‐response curves were constructed for the 6 most active compounds and characterized in terms of the IC50, the slope and the maximum response attainable relative to that of histamine.
Histamine, 2‐thiazolylethylamine and Nα‐methylhistamine produced a maximal or near maximal response. Nα,Nα‐dlmethylhistamine and 2‐methylhistamine appear to be partial agonists.
The response to all the agonists was practically abolished by mepyramine 1 μm, indicating that the response is mediated largely or wholly via histamine H1‐receptors.
The relative potencies of the agonists on cyclic AMP accumulation were in general similar to relative potencies in causing contraction of intestinal smooth muscle. The biggest difference was observed with Nα‐methylhistamine.
The histamine analogues were also examined as inhibitors of [3H]‐mepyramine binding in homogenates of guinea‐pig cerebral cortex. The inhibition curves were characterized in terms of IC50, the slope and the maximum percentage inhibition. This last value was compared with the inhibition produced by promethazine 2 μm.
For the 6 most potent agonists, the EC50 for cyclic AMP accumulation was compared with the IC50 against [3H]‐mepyramine binding, corrected for inhibition of non‐receptor binding and for competition with [3H]‐mepyramine. With the possible exception of 2‐pyridyletfiylamine, the values did not differ by more than a factor of 3.
Effects of the venom of the Brazilian scorpion (Tityus serrulatus) on the compound action potential of the rabbit vagus nerve fibres
Authors: Neto Francisco Riccioppo 
Published: July 2012

The effects of the venom of the scorpion (Tityus serrulatus) on nerve fibres of the rabbit cervical vagus were studied by the single sucrose‐gap technique. Scorpion venom (1 μg/ml) increased irreversibly the duration of the B component of the compound action potential of the vagus nerves, leaving the C component with its normal configuration. Tetrodotoxin (200 n m) supressed the prolongation of the action potential duration in venom‐treated B fibres.
At the same concentration (1 μg/ml), scorpion venom reduced the amplitude and the rate constant of decay of the hyperpolarization produced by tetanic stimulation of non‐myelinated nerve fibres.
A lower concentration (0.2 μg/ml) blocked completely the hyperpolarization of the potassium‐activated response. After washing, the potassium‐activated response partially recovered its amplitude but there was a significant increase in the time constant of the decay of hyperpolarization.
It is suggested that scorpion venom may modify the sodium pumping mechanism within fibres as well as affecting the passive and active sodium permeability systems.
Storage of biogenic amines in guinea‐pig brain synaptosomes: influence of proton gradient and membrane potential
Authors: Affolter H. , Peyer M. , Pletscher A. 
Published: July 2012

The effects of K+, NaCN and the ionophores monensin, nonactin and carbonyl‐cyanide‐p‐trifluoro‐methoxyphenylhydrazone (FCCP) on the contents of [3H]‐5‐hydroxytryptamine ([3H]‐5‐HT), [3H]‐dopamine and [3H]‐noradrenaline ([3H]‐NA) in guinea‐pig synaptosomes preloaded with these amines were measured.
In the presence of Ca2+, K+ markedly reduced the amine content of the synaptosomes, indicating an acceleration of spontaneous amine release. In the absence of Ca2+, K+ had much less effect.
Monensin, nonactin and FCCP caused a release of all the three labelled amines. This release was considerably faster and more marked than that induced by K+ and showed no dependence on Ca2+. The ionophores did not release lactate‐dehydrogenase from synaptosomes.
NaCN, a blocker of oxidative energy production, did not enhance the spontaneous release of [3H]‐5‐HT nor did it influence the monensin‐induced release of [3H]‐5‐HT.
It is concluded that (a) the intragranular storage of 5‐HT, dopamine and NA is dependent on the maintenance of a pH‐gradient across the granular membrane as well as on the granular membrane potential; (b) the ionophores cause a non‐exocytotic release of granular amines, and (c) blood platelets are partial models for aminergic brain neurones as far as intragranular amine storage is concerned.
In vivo characterization of histamine H1‐ and H2‐receptors in the rat stomach microcirculation
Authors: Koo A. 
Published: July 2012

Using a video microscope system, an in vivo microcirculation preparation was designed to characterize histamine receptors in the rat stomach submucosal arterioles (diameter 50 μm).
Each in vivo stomach microcirculation preparation received topically applied multiple concentrations of either the selective histamine H1‐ or H2‐ receptor agonist and antagonist and the respective responses (changes of the arteriolar diameter) were used to construct the concentration‐response curves.
Results showed that both 2‐thiazolylethylamine and impromidine, the respective selective H1‐and H2‐receptor agonists, produced concentration‐dependent vasodilator responses in the in vivo stomach submucosal arterioles. These vasodilator responses were competitively and selectively blocked by the respective H1‐receptor antagonist mepyramine and the H2‐receptor antagonist cimetidine.
Data from each in vivo preparation were examined separately to yield a Schild plot and a Hill plot, from which the in vivo estimates of the pA2 value, the slope of the Schild plot, and the Hill coefficient were obtained.
The estimated pA2 values for mepyramine (9.60 ± 0.033, mean ± s.e. mean) and cimetidine (5.98 ± 0.037) conformed to similar values found in other tissues, showing that the rat stomach microvascular H1‐ and H2‐receptors are of the same nature as similar receptors elsewhere.
Both the Hill and the Schild plots yielded regressions with unity slopes, indicating that the agonist‐receptor and the antagonist‐receptor reactions followed a simple one‐to‐one stoichiometry.
The findings in the present study are discussed and compared with those from other in vitro tissue preparations; it appears that the present in vivo technique is a satisfactory system for characterizing receptors in the vascular smooth muscle of the microcirculation.
The effects of yohimbine on presynaptic and postsynaptic events during sympathetic nerve activation in cattle iris: a critique of presynaptic receptor theory
Authors: Kalsner Stanley 
Published: July 2012

The effects of presynaptic α‐adrenoceptor blockade on both the efflux of 3H‐transmitter and on the magnitude of the effector response were measured simultaneously in a smooth muscle preparation which responds to field stimulation with noradrenergic β‐receptor‐mediated relaxation.
In the presence of atropine, the circular muscle of cattle iris relaxes in response to noradrenaline and to field stimulation at 2 Hz with 10, 20, 50 and 100 pulses:
Yohimbine (3 × 10−6M), a potent presynaptic α‐adrenoceptor antagonist, increased the stimulation‐induced efflux of tritium to about 2.0 times control values and, contrary to theory, did so to a similar extent regardless of pulse number and with apparent indifference to the synaptic concentration of transmitter, as confirmed by the varying size of the postsynaptic response.
In most cases, yohimbine had no significant effect on the magnitude of the relaxations to nerve stimulation.
It is concluded that negative feedback regulation of transmitter release, if it functions at all, and this itself seems doubtful, would not have a substantial impact on the size of the effector response.
Vitamin C increases the formation of prostacyclin by aortic rings from various species and neutralizes the inhibitory effect of 15‐hydroperoxy‐arachidonic acid
Authors: Beetens Johan R. , Herman Arnold G. 
Published: July 2012

Aortic rings from rats, rabbits and guinea‐pigs produce different amounts of 6‐oxo***‐prostaglandin F1α (6‐oxo‐PGF1α), the stable breakdown product of prostacyclin, i.e. 2760 ± 195, 160 ± 10 and 87 ± 17 pg 6‐oxo‐PGF1α per mg wet weight in 30 min.
Vitamin C enhances the production of 6‐oxo‐PGF1α by the aortic tissue of these three species, independent of their basal release. This increase was only significant if vitamin C was present in the preincubation as well as in the incubation fluid.
15‐Hydroperoxy‐arachidonic acid inhibits the production of 6‐oxo‐PGF1α (IC50:6 μm) and this inhibitory effect was completely neutralized by vitamin C.
The increased production of 6‐oxo‐PGF1α is not due to an increased release of the substrate arachidonic acid. It is suggested that vitamin C enhances the formation of 6‐oxo‐PGF1α by protecting the cyclo‐oxygenase and PGI‐synthase.
Indomethacin enhances the effect of histamine on airways resistance in the anaesthetized guinea‐pig
Authors: Mitchell H.W. 
Published: July 2012

In anaesthetized guinea‐pigs intravenous histamine caused an increase in airways resistance (RA) and a fall in dynamic compliance (CDyn).
Indomethacin (1 mg kg−1, i.v.) significantly enhanced the effect of histamine on RA. Indomethacin also increased the basal RA and the RA response to a histamine infusion. The effect of indomethacin on CDyn was less consistent but here also there was a trend for an increased response to histamine. Sodium carbonate (the vehicle for indomethacin, 0.05 ml 100 mm solution) had no effect on RA or CDyn in control experiments.
Propranolol (0.1 mg kg−1, i.v.) enhanced the effect of histamine on RA in animals pretreated with either indomethacin or Na2CO3 vehicle, but the effect was more consistent in indomethacin pretreated animals.
Indomethacin also tended to enhance the effect of histamine on RA in animals pretreated with reserpine or BW755c but it had little effect on the CDyn response to histamine.
The results show that indomethacin augments the responsiveness of the airways to histamine in the anaesthetized guinea‐pig. The results with propranolol and reserpine suggest that an operational β‐adrenergic system is not required for the effect of indomethacin on RA. No confirmation for lipoxygenase involvement was obtained with the lipoxygenase inhibitor, BW755.
Characterization of the opiate receptor population mediating inhibition of VIP‐induced secretion from the small intestine of the rat
Authors: Coupar Ian M. 
Published: July 2012

Net water transport was measured from the jejunum of anaesthetized rats by a re‐circulation technique.
Several narcotic analgesics were administered intravenously and assessed for activity in reversing net fluid secretion induced by intra‐arterial infusion of vasoactive intestinal peptide (VIP).
The μ‐opiate agonists, morphine, RX 783006 and FK 33–824 produced full reversal of the secretory phase of the VIP response, but failed to restore totally fluid transport to the control level of net absorption.
The κ‐agonist, ethylketocyclazocine, caused only partial reversal of VIP‐induced secretion while the more selective κ‐agonist, MR 2034, produced a small though non‐significant antisecretory effect at high doses. The δ‐agonist, d‐Ala2‐d‐Leu5‐enkephalin also had negligible antisecretory activity.
Naloxone caused a parallel displacement to the right of the antisecretory dose‐response line to morphine. The ‘in vivo PA2’ value of naloxone was 7.14.
The results are compared with previously published antinociceptive activities of the opiate agonists and in vivo pA2 values of naloxone. It is concluded that stimulation of μ‐opiate receptors mediates inhibition of VIP‐induced fluid secretion from the rat jejunal mucosa.
Age related changes in the antilipolytic effects of nicotinic acid in rat adipose tissue
Authors: Caparrotta L. , Fassina G. , Gaion R.M. , Tessari F. 
Published: July 2012

The effect of nicotinic acid on lipolysis was tested in vitro in adipose tissue from three groups of rats, selected according to age: 6–7 weeks, 10–12 weeks and 16–20 weeks old.
Although the changes were not statistically significant, the basal release of free fatty acid (FFA) was increased and glycerol was decreased by nicotinic acid (0.01–1 mm); the drug caused a statistically significant increase in basal FFA: glycerol ratio in a concentration‐dependent manner. This ratio also increased with age in the absence of drug.
(−)‐Noradrenaline (10 μm) and theophylline (3 mm) each stimulated lipolysis. When glycerol release was calculated as a percentage increase, the effects of these drugs became more marked with age. By contrast, the highest absolute rate of induced release occurred in adipose tissue from the youngest rats.
The lipolytic effect of 10 μm (−)‐noradrenaline was generally unaffected by nicotinic acid except in adipose tissue from the oldest rats when the glycerol release was reduced by 1 mm nicotinic acid, although it did not alter FFA: glycerol ratio.
The stimulation of glycerol release induced by 3 mm theophylline was not affected by the presence of nicotinic acid in the youngest rats, but the drug elicited a concentration‐dependent antilipolytic effect in adipose tissue from 10–12 weeks old rats, which was even more pronounced in the oldest animals. Lower theophylline concentrations (0.6–1 mm) were also sensitive to nicotinic acid inhibition in the 6–7 weeks old rats. In the presence of theophylline, nicotinic acid had no effect on FFA: glycerol ratio.
These data show a direct influence of age on the antilipolytic action of nicotinic acid.
Comparison of two calcium antagonists, verapamil and fendiline, in an experimental model of myocardial ischaemia mimicking classical angina on effort
Authors: Csik Vera , Szekeres L. , Udvary Eva 
Published: July 2012

The effects of verapamil (0.15/kg) and fendiline (3 mg/kg) were studied in anaesthetized, thoracotomised dogs with a critical constriction of the left anterior descending coronary artery, paced in excess of the initial rate by 60–70 beats/min. Epicardial ST‐segment elevation and changes in lactate uptake were used to assess the severity of myocardial ischaemia.
Both drugs prevented the ST‐segment elevation and the reduced lactate uptake that resulted from atrial pacing.
The anti‐ischaemic effect of fendiline is mainly due to its negative chronotropic action, whereas that of verapamil is due in part to bradycardia and in part to the reduced preload and afterload. In addition, both agents increase coronary flow to the ischaemic area and thus improve the myocardial oxygen supply/oxygen requirement ratio.
Effect of 6‐hydroxydopamine on bovine adrenal chromaffin cells in culture
Authors: Kirpekar S.M. , Nobiletti J. , Trifaró J.M. 
Published: July 2012

The effect of 6‐hydroxydopamine on the catecholamine content and cell morphology of bovine adrenal chromaffin cells in culture was investigated.
6‐Hydroxydopamine markedly reduced the catecholamine content of the cultured chromaffin cells after 6 and 24 h exposure. The effect was dose‐related, with half‐maximal depletion occurring at 2.4 × 10−5 M
Cells exposed to 6‐hydroxydopamine for 3 h and then to normal medium without the drug for 3 h more showed the same degree of toxicity as cells exposed to the drug for the entire 6 h.
Ascorbate at high concentrations also exhibited toxicity toward chromaffin cells between 6 and 24 h of exposure.
6‐Hydroxydopamine produced marked changes in cell morphology. At 1 h the cells appeared normal, at 3 h the processes were markedly shortened, and at 6 h they were completely retracted. On exposure for 24 h there were gross morphological changes and most cells were detached and free‐floating in the medium.
The toxicity of 6‐hydroxydopamine in bovine adrenal chromaffin cells is discussed.
Propranolol‐induced airway hyperreactivity in guinea‐pigs
Authors: Ney U.M. 
Published: July 2012

In anaesthetized, spontaneously breathing guinea‐pigs, enhanced bronchoconstrictor responses (↑ RL) to histamine were measured following intravenous injection of practolol, (±)‐propranolol, (+)‐ and (−)‐propranolol.
Propranolol enhanced not only histamine‐ but 5‐hydroxytryptamine (5‐HT)‐induced bronchoconstrictions and its effects lasted up to 2 h.
This increased airway sensitivity was not due to β‐adrenoceptor blockade because: (a) similar effects were produced by racemic propranolol and its two isomers (+)‐ and (−)‐propranolol and (b) whilst equal doses of (±)‐ and (+)‐propranolol produced the same potentiation of histamine bronchoconstriction, only (±)‐propranolol also caused a measurable β‐adrenoceptor blockade in the airways.
The enhanced histamine‐ and 5‐HT‐induced bronchoconstrictions were antagonized by the leukotriene antagonist FPL 55712 and by the lipoxygenase/cyclo‐oxygenase inhibitor BW755c.
The results demonstrate that endogenously released leukotrienes can produce not only a direct bronchospasm but may enhance the effects of other bronchoconstrictor agents.
The relevance of this leukotriene‐mediated hyperreactivity to the non‐specific airway hyperreactivity seen in asthmatics is discussed.