bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of collagenase on the release of [3H]‐noradrenaline from bovine cultured adrenal chromaffin cells
Authors: Almazan G. , Aunis D. , García A.G. , Montiel C. , Nicolás G.P. , Sánchez‐García P. 
Published: July 2012

Bovine isolated adrenal chromaffin cells maintained in culture at 37°C for 1–7 days become polygonal and bipolar, with typical varicosity‐like extensions. Catecholamine levels and dopamine β‐hydroxylase activity decreased after 24–48 h of culture, but recovered to normal levels 3–7 days later.
Incubation of 1–7 day‐old cells in the presence of increasing concentrations of [3H]‐noradrenaline (3.91 to 125 nm) resulted in the retention by the cells of amounts of radioactivity directly proportional to the amine present in the media. One day‐old cells took up and retained only one third of the radioactivity found in 2–7 day‐old cells.
The addition of collagenase to cultured cells caused a decrease in the uptake of tritium. However, the enzyme treatment did not affect the amine taken up by the cell before collagenase treatment.
Release of tritium from cultured cells evoked by nicotine, acetylcholine (ACh) or 59 mm K+ was very poor in 24 h‐old cells; the secretory response to nicotine, ACh or K+ was dramatically increased after 2–7 days of culture. Bethanecol did not cause any secretory response.
When treated with collagenase, cultured cells which had recovered fully their secretory response, lost again the ability to release tritium evoked by ACh or nicotine. However, the responses to high K+, veratridine or ionophore X537A were not affected. The nicotinic response was recovered two days after collagenase treatmen.
The data suggest that the use of collagenase to disperse the adrenomedullary tissue during the isolation procedure might be responsible for the lost secretory response of young cultured chromaffin cells. Since collagenase specifically impairs the nicotinic cholinoceptor‐mediated catecholamine release, it seems likely that the enzyme is exerting its action on the ACh receptor complex. It is unlikely that either voltage‐sensitive Na+ or Ca2+ channels are affected by collagenase as the responses induced by high K+ or veratridine were unaffected by this enzyme.
The importance of endogenous prostaglandins other than prostacyclin, for the modulation of contractility of some rabbit blood vessels
Authors: Förstermann U. , Hertting G. , Neufang B. 
Published: July 2012

Helically cut strips of rabbit aorta, extrapulmonary artery, coeliac artery, and femoral artery were set up in organ baths. Contractions of the strips by noradrenaline and angiotensin II were recorded isotonically. The release of prostaglandins 6‐keto‐PGF1α, E2, F2α, D2 and thromboxane B2 from the strips was measured by means of sensitive and specific radioimmunoassays.
All blood vessels released a characteristic pattern of cyclo‐oxygenase products. Prostacyclin (PGI2, measured as 6‐keto‐PGF1α) was the major compound formed, followed by smaller amounts of PGE2 and traces of PGF2α, PGD2 and thromboxane A2 (measured as thromboxane B2). The pulmonary and the femoral artery had comparatively high abilities to synthesize PGE2.
Contractions induced by noradrenaline increased prostaglandin release from the pulmonary artery but not from the other blood vessels. Angiotensin II‐induced contractions were accompanied by a marked prostaglandin release from the coeliac artery. After angiotensin II, prostaglandin release was also enhanced in the pulmonary artery, but remained essentially unchanged in the aorta and femoral artery.
Arachidonic acid markedly increased the levels of all prostaglandin formed.
Indomethacin inhibited the formation of all prostaglandins below the detection limits of the respective radioimmunoassays.
Indomethacin treatment induced a qualitatively similar shifting of the concentration‐response curves of noradrenaline and angiotensin II in some vessels: the concentration‐response curves remained unchanged for the aorta, were slightly shifted to the left of the pulmonary artery, were markedly shifted to the left for the coeliac artery, and were shifted to the right for the femoral artery.
Exogenous PGI2 strongly and concentration‐dependently inhibited contractions induced by the approximate EC50 of noradrenaline in the coeliac artery, but was without effect on the other three preparations. PGE2 had no effect on noradrenaline‐induced contractions of the aorta, inhibited those of the pulmonary and the coeliac artery, but markedly potentiated those of the femoral artery. PGF2α significantly enhanced contractions of the femoral artery, but increased contractions of the other preparations were not significant. PGD2 was without effect on any preparation.
In conclusion, the contractility of the aorta does not seem to be modulated substantially by prostaglandins. The major prostanoid regulating the tone of the coeliac artery was found to be PGI2. The contractility of the pulmonary and especially the femoral artery is probably not modulated by PGI2 but rather by PGE2.
These observations suggest that in certain blood vessels, prostaglandins other than PGI2 are important endogenous modulators of contractility.
The actions of antipsychotic drugs on dopamine receptors in the rat substantia nigra
Authors: Pinnock R.D. 
Published: July 2012

The activity of neurones in the zona compacta of the rat substantia nigra was recorded extracellularly in vitro. Dopamine produced a dose‐dependent depression of firing, threshold doses being in the 3 μm range.
The inhibitory effects of dopamine were antagonized by (−)−sulpiride (pA27.5), haloperidol (pA28.4) and cis‐flupenthixol (pA26.9). The actions of γ‐aminobutyric acid (GABA) were not affected by these compounds.
The gradients of Schild plots of data for (−)−sulpiride were less than unity while those for haloperidol and cis‐flupenthixol were greater than unity, which suggests that the antagonism was not competitive. This is discussed with regard to the use of a bioassay system in the analysis of the effects of antagonists.
Haloperidol and (−)−sulpiride were found to have similar potencies, as dopamine receptor antagonists, to those predicted from biochemical and clinical efficacy studies, but cis‐flupenthixol was less potent than expected.
Induction of hypoglycaemia and accumulation of 5‐hydroxytryptamine in the liver after the injection of mitogenic substances into mice
Authors: Endo Yasuo 
Published: July 2012

Various mitogenic substances (concanavalin A, pokeweed mitogen, polyl: polyC and a phorbol diester), as well as lipopolysaccharides (LPS or endotoxins), produced hypoglycaemia after being injected into mice. However, non‐mitogenic immuno‐stimulants (zymosan, carrageenan, an adjuvant peptide and interferon) did not induce hypoglycaemia.
All of the mitogenic substances also induced an increase in 5‐hydroxytryptamine (5‐HT) in liver, but the non‐mitogenic substances did not have this effect.
The time course of the development of hypoglycaemia was similar to that of the increase in liver 5‐HT.
The dose‐dependence of the hypoglycaemia induced by LPS was similar to that of the increase in liver 5‐HT.
In C3H/HeJ mice, the macrophages and/or lymphocytes of the mice are known to be less responsive to LPS, and both the LPS‐induced hypoglycaemia and increase in 5‐HT were less in these mice than in control mice (C3H/He and ddI mice).
These results suggest that macrophages and/or lymphocytes may participate in the induction of hypoglycaemia and the increase in 5‐HT induced by mitogenic substances and LPS. A possible correlation between hypoglycaemia and the increase in hepatic 5‐HT is discussed, although the relationship is not substantiated.
Cyclic GMP mediates neurogenic relaxation in the bovine retractor penis muscle
Authors: Bowman Anne , Drummond Alan H. 
Published: July 2012

Field stimulation of the non‐adrenergic, non‐cholinergic inhibitory nerves to the bovine isolated retractor penis muscle evoked a relaxation that was preceded by a rise in the tissue content of cyclic GMP. There was no change in the content of cyclic AMP.
The selective cyclic GMP phosphodiesterase inhibitor, 2‐o‐propoxyphenyl‐8‐azapurin‐6‐one (M&B 22948), elevated the tissue's cyclic GMP content, and potentiated both the relaxation and the rise in cyclic GMP produced by inhibitory nerve stimulation.
Sodium nitroprusside and an inhibitory factor extracted from the bovine retractor penis muscle mimicked the effects of inhibitory nerve stimulation in that they each produced relaxation associated with a selective rise in cyclic GMP concentration.
Haemoglobin (in the form of erythrocyte haemolysate) and N‐methylhydroxylamine, which are known to block guanylate cyclase, blocked the relaxation and the rise in cyclic GMP content produced by inhibitory nerve stimulation, inhibitory factor and sodium nitroprusside. Haemoglobin itself caused a rise in muscle tone and at the same time reduced the cyclic GMP content of the tissue.
8‐Bromocyclic GMP, a permeant derivative of cyclic GMP, produced a relaxation of the muscle that, as expected, was not blocked by haemoglobin.
Vasoactive intestinal polypeptide, prostaglandin E1 and forskolin each produced relaxation associated with a selective rise in cyclic AMP content. Their effects were not blocked by haemoglobin or N‐methylhydroxylamine.
It is concluded that inhibitory nerve stimulation in the bovine retractor penis muscle produces a relaxation that is mediated by cyclic GMP, although some substances relax the muscle without affecting cyclic GMP levels. The results are also compatible with the view that the extracts of muscle contain the inhibitory neurotransmitter.
Triggering by Paf‐acether and adrenaline of cyclo‐oxygenase‐independent platelet aggregation
Authors: Fouque F. , Vargaftig B.B. 
Published: July 2012

Platelet‐activating factor (Paf‐acether, 1‐alkyl‐2‐acetyl‐sn‐glycero‐3‐phosphorylcholine) induced full aggregation and a limited release reaction of human platelets in plasma or in blood.
Cyclo‐oxygenase inhibition with aspirin only reduced aggregation when induced by threshold amounts of Paf‐acether, whereas higher concentrations surmounted inhibition whether tested in citrated or in heparinized platelet‐rich plasma or blood. Aspirin‐induced inhibition of platelet secretion by Paf‐acether was insurmountable and independent of the anti‐coagulant used.
Paf‐acether and adrenaline acted synergistically in inducing aggregation in citrate and in heparin. Aspirin in vitro or after oral ingestion at doses that suppressed aggregation induced by arachidonic acid alone, failed to reduce significantly the synergized aggregation induced by Paf‐acether alone or combined with adrenaline. Twenty‐four hours after the oral ingestion of aspirin, when aggregation by arachidonic acid remained blocked, a slight inhibitory activity on the effect of Paf‐acether noted 4 h after aspirin, had ceased. This was probably accounted for by the synthesis of thromboxane A2 by newly formed platelets, since the in vitro addition of aspirin, or of the thromboxane/endoperoxide receptor inhibitor 13‐azaprostanoic acid caused the 24 h platelets to behave in a manner similar to platelets collected 4 h after aspirin.
The α2‐adrenoceptor inhibitor, yohimbine, blocked the direct effect of adrenaline as well as its synergism with Paf‐acether.
Since the synergistic effect of Paf‐acether and adrenaline was maintained when thrombin‐degranulated platelets were used, and aspirin remained ineffective against it, it is clear that the augmented platelet responsiveness is not accounted for by the platelet release reaction.
Paf‐acether and adrenaline act synergistically and stimulate platelets by cyclo‐oxygenase‐independent mechanisms, which may be relevant in human physiopathological conditions.
Effects of isoprenaline on the contraction‐relaxation cycle in the cat trachea
Authors: Ito Yushi , Itoh Takeo 
Published: July 2012

Effects of isoprenaline (Isop) on the contractile properties of the smooth muscle cells of cat trachea were investigated using intact and chemically skinned muscle preparations and an isometric tension recording method.
In the intact muscle preparations, Isop 3 × 10−10 or 3 × 10−9m significantly suppressed the amplitude of tonic contractions evoked by acetylcholine (ACh) 10−7 m or 10−5 m, respectively.
Following treatment of the tissue with Ca2+ ‐free 2 mm EGTA‐containing solution after depletion of stored Ca2+ with caffeine, 2.5 mm Ca2+ was applied for 5 min (procedure 1), and subsequently 10 mm caffeine was applied in Ca2+‐free 2 mm EGTA containing solution. The object was to estimate the amount of stored Ca2+ during procedure 1 from the amplitude of the caffeine (10 mm)‐induced contraction (procedure 2).
Isop, applied during procedure 1, did not affect the amplitude of the caffeine‐induced contraction; however, when applied during procedure 2, this agent (10−8m) significantly suppressed the amplitude of the caffeine‐induced contraction to about 90% of the control value.
ACh (10−5m), applied during procedure 1, evoked phasic and tonic contractions. Isop (10−8m), applied simultaneously with ACh (10−5m), suppressed the amplitude of the ACh‐induced contraction yet increased the amplitude of contraction evoked by the subsequent application of caffeine 10 mm (procedure 2).
Effects of conditioning application of ACh (10−7 or 10−5m) on the caffeine‐induced contraction were observed in the presence or absence of Isop during procedure 2. When ACh 10−5m was used, subsequent application of caffeine 10 mm evoked no mechanical response, in control conditions. However, after the pretreatment of the tissue with Isop during procedure 2, the amplitude of the ACh (10−5m)‐induced contraction was not affected, yet the subsequent application of caffeine (10 mm) evoked minute but discrete contractions, indicating that Isop did enhance the sequestration of free Ca2+ into the storage sites.
In the saponin‐treated skinned muscles, the minimum concentration of Ca2+ required to produce contraction was 1 × 10−7m, and the maximum contraction was obtained with 1 × 10−5m Ca2+. Isop (10−6m) had no effect on the relationship between free‐Ca2+ and the amplitude of the contraction. However, simultaneous application of high concentrations of cyclic AMP (10−4m) and cyclic AMP‐dependent protein kinase (50 μg ml−1) significantly suppressed contractions evoked by 3 × 10−7 or 10−5m Ca2+.
These results indicate that Isop suppresses the contraction evoked by various agonists in the cat trachea, mainly through sequestration of Ca2+ into the intracellular storage sites, rather than by direct or indirect (through cyclic AMP) actions on the contractile proteins.
Solubilization of dopamine‐D2receptors from synaptosomal membranes of the bovine caudate nucleus
Authors: Kidrič Marjetka , Petrović Jelena , Šoškić V. , Trajković Divna 
Published: July 2012

Dopamine D2‐receptors were solubilized from synaptosomal membranes of the bovine caudate nucleus using different detergents. They were labelled with [3H]‐spiperone and assayed by polyethylene glycol precipitation.
CHAPS was found to be the best solubilizing agent among all detergents used. Optimal conditions for solubilization were: 0.25% CHAPS, 3.5 mg ml−1 protein, 25 min, 4 °C and the yield of D2‐receptors was 18.6%.
Addition of some sulphobetain detergents increased the extent of solubilization, 125 mm NaCl and 0.25 m sucrose decreased it, while SH‐group protecting agents (2 mm dithiothreitol and 6 mm β‐mercaptoethanol), as well as MEGA‐9 and MEGA‐12 were almost ineffective.
—log IC50 values for solublized dopamine D2‐receptors are in linear correlation with the corresponding values for membrane‐bound receptors (r = 0.962, slope factor 0.96) and Kd value of solubilized receptors was 3.61 ± 0.94 nm, while that of membrane‐bound receptors was 1.25±0.10 nm.
Specific binding of [3H]‐spiperone to the solubilized receptors resolved by linear sucrose density gradient centrifugation shows two maxima, one in the first several fractions from the bottom and the other with an apparent 5 value of 7.3.
The antagonism of histamine‐induced tracheal and bronchial muscle contraction by diphenhydramine: effect of maturation
Authors: Douglas James S. , Duncan Pamela G. , Mukhopadhyay Asoke 
Published: July 2012

Airway reactivity in spontaneously breathing unanaesthetized female guinea‐pigs was significantly reduced as a consequence of maturation. Threshold doses to histamine (% w/v base) were 0.08% ± .01 and 0.27% ± .04 in immature (110g ± 2; 1 week old) and mature (837 g ± 29; 4 months old) animals, respectively.
The potency of 2‐(2‐thiazolyl) ethylamine in tracheal tissues from mature animals was significantly less than that in tissues from immature animals (5.06 ± .03 vs 5.26 ± .07). There was no change in the potency of this agonist in bronchial tissues (5.0 ± .09 vs 4.9 ± .13).
Diphenhydramine reduced tissue contractility in tracheal (30% at 0.1 μm; 50% at 3 μm) but not bronchial tissues. The antihistamine in concentrations ranging from 0.1 μm to 3 μm reduced the potency of histamine 2 to 50 fold in both tissues.
Schild plots were linear but slopes were significantly less than unity. pA2 values ± 95% fiducial limits derived from data from tracheal tissues of immature and mature animals using constrained Schild plots (unit slope) were 7.7 (7.6−7.7) and 7.1 (7.0−7.2), respectively (P<0.05). pA2 values for diphenhydramine in bronchial tissues using constrained Schild plots were 7.8 (7.7−7.9) and 7.5 (7.3−7.5), respectively (P<0.05).
The data emphasize the unique nature of tracheal and bronchial tissues. We conclude that, with maturation, the characteristics of the histamine receptor change. We suggest that the remission of asthma which frequently occurs at puberty may be related to alteration in the properties of membrane receptors.
Selectivity and potency of 2‐alkyl analogues of the α2‐adrenoceptor antagonist idazoxan (RX 781094) in peripheral systems
Authors: Doxey J.C. , Roach A.G. , Strachan Diane A. , Virdee Narinder K. 
Published: July 2012

The profiles of four analogues of idazoxan have been examined at α‐adrenoceptors and the results compared to those obtained with idazoxan and yohimbine. The compounds possessed either a methyl (RX 801079), ethyl (RX 811033), n‐propyl (RX 811054) or isopropenyl (RX 811005) group at the two position of idazoxan.
The rank order of antagonist potency against UK‐14,304 at prejunctional α2‐adrenoceptors of the rat isolated vas deferens was RX 811054 > RX 811033 > idazoxan > RX 811005 > yohimbine = RX 801079. All compounds were competitive antagonists.
The rank order of antagonist potency against noradrenaline at postjunctional α1‐adrenoceptors of the rat isolated anococcygeus muscle was RX 811054 = RX 811033 = idazoxan = yohimbine > RX 811005 = RX801079. All compounds were competitive antagonists. The rank order of α‐adrenoceptor selectivity (α2/α1) was RX 811005 > RX 801079 > RX 811054 > RX811033 > idazoxan > yohimbine.
In pithed rats, intravenous administration of all compounds fully reversed the prejunctional α2‐adrenoceptor agonist effects of clonidine and guanabenz on electrically‐induced contractions of the vas deferens and anococcygeus muscle respectively.
In pithed rats the rank order of antagonist potency against UK‐14,304 at cardiac prejunctional α2‐adrenoceptors was RX 811054 > RX811033 > idazoxan > yohimbine > RX811005 > RX 801079. In contrast, the rank order of antagonist potency against cirazoline pressor effects (vascular postjunctional α1‐adrenoceptors) was RX 811054 > RX 811033 > yohimbine > idazoxan > RX 811005 > RX 801079. The rank order of α2‐adrenoceptor selectivity was RX 811033 = RX 801079 = RX 801005 > RX 811054 > idazoxan > yohimbine.
Although idazoxan produced contractions of the anococcygeus muscle and increased blood pressure in pithed rats, three of the analogues (RX 811005, RX 801079 and RX 811033) were inactive.
In conclusion, alkyl substitution in the 2‐position of idazoxan can enhance either α2‐adrenoceptor antagonist potency or selectivity or both and furthermore, the weak partial α1‐adrenoceptor agonist properties of idazoxan can be removed.
Role of metabolism in the immediate effects and pneumotoxicity of 3‐methylindole in goats
Authors: Breeze R.G. , Laegreid W.W. , Olcott B.M. 
Published: July 2012

Rapid infusion of 3‐methylindole (3‐MI) dissolved in 10% Cremophor EL in water was immediately followed by pulmonary arterial hypertension, systemic arterial hypotension, decreased minute volume and periods of apnoea in goats.
Rapid intravenous infusion of Cremophor EL/water alone caused similar immediate effects to those of Cremophor EL plus 3‐MI in various dosages.
Pretreatment of goats with piperonyl butoxide or phenobarbitone did not significantly alter these immediate cardiopulmonary responses. But pretreatment with piperonyl butoxide prevented clinical signs and pulmonary lesions of 3‐MI toxicity, whereas phenobarbitone pretreatment shortened survival time and enhanced pulmonary pathology.
Cremophor EL and 3‐MI dissolved in Cremophor EL caused severe in vitro haemolysis of caprine and bovine erythrocytes.
There was no relationship between the immediate effects of 3‐MI and the subsequent development of 3‐MI‐induced pneumotoxicity and deaths in control goats or in goats pretreated with piperonyl butoxide or phenobarbitone. Induction or inhibition of mixed function oxidase activity had no influence on immediate responses to 3‐MI but did change the severity of clinical and pathological responses.
It is concluded that there is no apparent relationship between the immediate and the pneumotoxic effects of 3‐MI. It is possible that the immediate effects are the result of intravascular haemolysis.
Effect of chemical destruction of adrenergic neurones on some cholinergic mechanisms in adult rat sympathetic ganglia
Authors: Collier B. , Johnson G. , Quik M. , Welner S. 
Published: July 2012

Rats were treated for 2–6 weeks with guanethidine after which their superior cervical ganglia were removed.Ganglionic tyrosine hydroxylase and α‐bungarotoxin binding sites were reduced by the guanethidine treatment indicating adrenergic cell body destruction.Choline acetyltransferase activity and acetylcholine content of ganglia were not clearly changed by the guanethidine treatment, indicating that the drug does not destroy presynaptic terminals and that these presynaptic indicators do not adapt markedly to postsynaptic loss.The Cholinesterase in the ganglia was reduced by guanethidine treatment, but such ganglia retained their ability to accumulate surplus acetylcholine when they were incubated with physostigmine. This is interpreted as indicating surplus acetylcholine accumulation is a presynaptic phenomenon.Choline uptake by resting ganglia was not reduced as a result of guanethidine treatment nor was it affected by preganglionic denervation. This is interpreted as indicating that during rest, choline uptake is into supporting cells or intraganglionic cells rather than cholinergic nerve terminals or adrenergic cell bodies.