bluuebunny/crossref_metadata_2025_split huggingface dataset:
LEUKOTRIENE B4: BIOLOGICAL ACTIVITIES AND THE CYTOSKELETON
Authors: CUNNINGHAM F.M. , SMITH M.J.H. 
Published: July 2012

The aggregation and chemokinesis of either rat or human polymorphonuclear leucocytes (PMNs) induced by leukotriene B4 isomer III (LTB4) are inhibited significantly by colchicine (10−6‐10−3m) and vinblastine (10−7‐10−4m). Random migration of the leucocytes is inhibited by colchicine 10−3m and vinblastine 10−4m.
Cytochalasin B (4 × 10−7‐4 × 10−6m) caused the aggregation of rat PMNs but inhibited their random migration. The aggregation of the PMNs induced by LTB4 was enhanced by cytochalasin B but the chemokinesis was inhibited.
It is suggested that both microtubules and microfilaments may be involved in the aggregatory and chemokinetic responses of PMNs to LTB4.
EFFECTS OF PROSTAGLANDINS AND THROMBOXANE ANALOGUES ON BULLOCK AND DOG IRIS SPHINCTER PREPARATIONS
Authors: DONG Y.J. , JONES R.L. 
Published: July 2012

The bullock iris sphincter was contracted by low concentrations of prostaglandin E2 (PGE2), 16,16‐dimethyl PGE2 and 17,18,19,20‐tetranor‐16‐p‐chlorophenoxy PGE2. Other compounds with thromboxane‐like actions, for example 11,9‐epoxymethano PGH2, were also potent spas‐mogens. ZK 36374, a stable carbacyclin, was a partial agonist on the PGE‐sensitive system of this tissue.
The thromboxane antagonist, EP 045, had little effect on the action of PGE2 and 16,16‐dimethyl PGE2 on the bullock iris.
The dog iris sphincter was sensitive to PGF2α but not to PGE2 and 11,9‐epoxymethano PGH2.
16,16‐Dimethyl PGE2 had very low activity on the dog iris in contrast to its high activity on the bullock iris. The reverse was found with the 17,18,19,20‐tetranor‐16‐m‐trifluoromethylphenoxy analogue of PGF2α (ICI 81008). This indicates a considerable selectivity of action of the two analogues.
The results are discussed in relation to the existing knowledge of prostanoid receptors.
GENERATION OF LEUKOTRIENE B4, ITS ALL trans ISOMERS AND 5‐HYDROXYEICOSATETRAENOIC ACID BY RAT BASOPHILIC LEUKAEMIA CELLS
Authors: FORD‐HUTCHINSON A.W. , PIPER PRISCILLA J. , SAMHOUN MARWA N. 
Published: July 2012

When rat basophilic leukaemia (RBL‐1) cells were incubated for 4 min, in the presence of arachidonic acid (AA) and calcium ionophore A23187, three isomers of leukotriene (LT) B4 and 5‐hydroxyeicosatetraenoic acid (5‐HETE) were generated.
The isomers of LTB4 separated by reverse phase high pressure liquid chromatography (h.p.l.c.) were found to be 5(S),12(S)‐dihydroxy‐6,14‐trans‐8,10‐trans‐eicosatetraenoic acid; 5(S), 12(R)‐dihydroxy‐6,14‐trans‐8,10‐trans‐eicosatetraenoic acid and 5(S),12(R)‐dihydroxy‐6,14‐cis‐8,10‐trans‐eicosatetraenoic acid or LTB4.
5(S), 12(R)‐cis, trans, trans‐LTB4 produced by RBL‐1 cells caused aggregation of rat polymorphonuclear leucocytes (PMNs). Its other two isomers (5(S), 12(S)‐all trans‐LTB4; 5(S),12(R)‐all trans‐LTB4) were much less active and 5‐HETE was found to be inactive.
5(S),12(R)‐cis, trans, trans‐LTB4 formed from RBL‐1 cells contracted guinea‐pig parenchymal strips (GPPs) and was indistinguishable from synthetic 5(S),12(R)‐cis, trans, trans‐LTB4. The other two isomers of LTB4, i.e. 5(S),12(S)‐all trans‐LTB4 and 5(S),12(R)‐all trans‐LTB4 as well as 5‐HETE were inactive on GPP.
RBL‐1 LTB4 was equipotent with LTD4, in most experiments, in contracting GPP but had no activity on guinea‐pig ileum smooth muscle (GPISM).
RBL‐1 cells contain the enzyme systems necessary for generating LTB4 as well as the leukotriene(s) with amino acid residues at C‐6.
ADENOSINE 5′‐DIPHOSPHATE ANTAGONISTS AND HUMAN PLATELETS: NO EVIDENCE THAT AGGREGATION AND INHIBITION OF STIMULATED ADENYLATE CYCLASE ARE MEDIATED BY DIFFERENT RECEPTORS
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; it has been suggested that these two effects are mediated by separate ADP receptors on the platelet surface.
Adenosine 5′‐triphosphate and seven adenine nucleotide analogues were tested as inhibitors of both effects of ADP on human platelets, and were found to be competitive.
pA2 values were calculated for each antagonist for inhibition of both effects of ADP, and a good correlation (correlation coefficient 0.87; P < 0.01) was found between the pA2 values for inhibition of ADP‐induced aggregation and the pA2 values for inhibition of the effect of ADP on stimulated adenylate cyclase.
Such a correlation does not support the suggestion that ADP‐induced aggregation and the inhibition by ADP of stimulated adenylate cyclase are mediated by two separate receptors.
CATECHOLAMINE TRANSPORT IN ISOLATED LUNG PARENCHYMA OF PIG
Authors: GOLDIE ROY G. , PATERSON JAMES W. 
Published: July 2012

Lung parenchyma strips of the pig incubated at 37°C with [3H]‐(−)‐noradrenaline ([3H]‐NA) or [3H]‐(±)‐isoprenaline ([3H]‐Iso), accumulated radioactivity via saturable, high affinity uptake processes. Apparent saturation constants (Km) for [3H]‐NA and [3H]‐Iso were 1.34 × 10−6 m and 1.63 × 10−6 m respectively, while apparent transport maxima (Vmax) were 4.86 and 1.63 × 10−9 mol min−1 g−1 respectively.
Cellular accumulation of radioactivity from radiolabeled catecholamines was greatly reduced by lowering the temperature to 7°C, pre treatment with ouabain (100 μm), phentolamine (15 μm) or phenoxybenzamine (80 μm). However, accumulation of radioactivity derived from (3H]‐NA was inhibited selectively by cocaine (10 μm) and desipramine (1 μm), while normetanephrine (80 μm) and 3‐O‐methylisoprenaline (50 μm) caused much greater reductions in cellular radioactivity from [3H]‐Iso than from (3H]‐NA. Taken together with information from kinetic studies, the results indicate that these amines are transported by separate uptake processes.
Cocaine (50 μm) which selectively reduced [3H]‐NA transport, had no significant effect on the sensitivity (EC50) of isolated parenchyma lung strips of the pig to the contractile effects of cumulative concentrations of NA. The catechol‐O‐methyl transferase (COMT) inhibitor, U‐0521 (60 μm), also failed to alter the potency of NA, while normetanephrine (80 μm) caused a 2 fold decrease in potency.
Phentolamine (15 μm), which reduced the cellular accumulation of radioactivity derived from [3H]‐Iso by 64%, caused a small potentiation of Iso‐induced relaxations of porcine lung strips. Normetanephrine (80 μm) and 3‐O‐methylisoprenaline (50 μm), which also depressed the accumulation of cellular radioactivity from [3H]‐Iso by > 50%, caused rightward shifts in Iso concentration‐effect curves as a result of β‐adrenoceptor blockade. In sharp contrast, cortisol (80 μm) and U‐0521 (60 μm), which caused smaller reductions in the cellular accumulation of radioactivity derived from [3H]‐Iso, both caused an approximately 9 fold potentiation of responses to Iso in isolated lung strips.
The results indicate that the major sites of uptake and metabolism of NA in porcine parenchyma strip are remote from α‐adrenoceptors mediating NA‐induced contraction. Similarly, some major sites of uptake of Iso are remote from β‐adrenoceptors mediating Iso‐induced relaxation. However, β‐adrenoceptors are apparently in close proximity to a compartment containing COMT activity.
AN ASSESSMENT OF THE EFFECTIVENESS OF NEONATAL TREATMENT WITH GUANETHIDINE AS A MEANS OF PRODUCING SYMPATHECTOMY
Authors: BENNETT T. , GARDINER S.M. , KEMP P.A. 
Published: July 2012

Male Wistar rats were treated neonatally with guanethidine (following a protocol reported to produce a permanent peripheral sympathectomy) and the extent of the sympathectomy was assessed when the rats were mature.
The noradrenaline content of right and left atria and the ventricles was markedly reduced in 9‐ and 26‐week old rats which had been treated with guanethidine. The extent of depletion in the ventricles was similar at both times but the atrial content increased between 9 and 26 weeks.
Arterial blood pressures were not significantly different in 24–26‐week old conscious rats which had been treated neonatally with guanethidine compared to controls, but the baroreflex sensitivity, assessed by the lengthening of pulse interval in response to a pressor stimulus, was significantly less in the guanethidine‐treated rats.
The blood pressure response to acute bilateral adrenalectomy was similar in control and guanethidine‐treated rats.
Left atria and hepatic portal veins taken from 20–26‐week old rats which had been treated with guanethidine showed classical signs of a denervation supersensitivity, but the chronotropic responses of right atria to noradrenergic nerve stimulation and to noradrenaline were normal.
Fluorescence histochemical studies on the right atria, irides and hepatic portal veins showed that the neonatal treatment had caused a variable degree of destruction both between and within animals.
The findings are consistent with neonatal guanethidine treatment causing extensive damage to peripheral noradrenergic nerves. However, the sympathectomy is neither complete nor permanent. In the heart, there appears to be a selective re‐innervation of the atria.
Despite the impaired efferent sympathetic nerve activity in rats treated neonatally with guanethidine, compensatory mechanisms permit adequate cardiovascular control in the resting state.
EFFECTS OF KETAMINE AND OF HIGH PRESSURE ON THE RESPONSES TO γ‐AMINOBUTYRIC ACID OF THE RAT SUPERIOR CERVICAL GANGLION in vitro
Authors: LITTLE HILARY J. 
Published: July 2012

The method of Brown & Marsh (1974) for recording of surface potentials from the rat superior cervical ganglion has been adapted for use in a high pressure chamber in order to study the effects of high pressure of helium and the possible interactions with the effects of general anaesthetics.
Helium pressure of 130 atm did not alter the amplitude of the responses recorded from the ganglion in response to γ‐aminobutyric acid (GABA) application (9.7 and 19.4 μm) but the amplitude of responses to a nicotinic agonist were depressed.
Ketamine, at concentrations between 18 and 180 μm, considerably potentiated the responses of the ganglion to GABA.
Helium pressure (130 atm) did not reverse the potentiation of GABA by ketamine.
The results are discussed in connection with the ability of ketamine to oppose the behavioural effects of high pressure.
ELECTROPHYSIOLOGICAL EFFECTS OF PIPERAZINE AND DIETHYLCARBAMAZINE ON Ascaris suum SOMATIC MUSCLE
Authors: MARTIN R.J. 
Published: July 2012

Electrophysiological recordings were made from the bag region of Ascaris suum muscle. Membrane potential and input conductance or membrane current under voltage clamp were measured.
In high‐Cl‐ Ringer, bath‐applied piperazine, at concentrations greater than 10−4 m, produced a dose‐dependent and reversible increase in input conductance associated with a hyperpolarizing potential. The increase in input conductance was reduced when the preparations were bathed in low‐Cl‐ Ringer. γ‐Aminobutyric acid (GABA) and piperazine reversal potentials were measured with a voltage clamp on the same cells using iontophoretic application of the agonists. The reversal potentials were the same and close to the predicted Nernst Cl‐ potential (—65 mV). When GABA and piperazine were applied simultaneously piperazine reversibly reduced the amplitude of the control outward GABA current response. It was concluded that piperazine acts as a GABA agonist of low potency on the extra‐synaptic GABA receptors of the bag, mediating an increase in Cl‐ conductance.
Acetylcholine was applied iontophoretically within 100 μm of the bag region while the preparation was bathed in a low‐Ca2+, low‐Cl‐ Ringer. The response under voltage clamp was a dose‐dependent inward current associated with an increase in input conductance. This response was reversibly antagonized by 3 × 10−5 m tubocurarine, high concentrations of diethylcarbamazine (10−3 to 10−2 m) but not high concentrations of piperazine (10−3 to 10−2 m). It was concluded that there are extra‐synaptic acetylcholine receptors on the bag region of Ascaris muscle and that diethylcarbamazine but not piperazine acts as an antagonist.
Bath‐applied diethylcarbamazine (10−4 to 2 × 10−3m) produced a reversible dose‐dependent depolarization of the membrane potential which was associated with an increase in the amplitude and frequency of spontaneous depolarizing potentials in active preparations at 32°C to 35°C in high‐Cl‐ Ringer. The excitatory action of diethylcarbamazine was not blocked by 3 × 10−5m tubocurarine. Diethylcarbamazine (10−4 to 10−3 m) had no effect on the outward current response to GABA iontophoresis. Diethylcarbamazine (10−4 to 10−2m) reversibly antagonized in a dose‐dependent manner the delayed rectification of the bag membrane. In a low‐Ca2+, low‐Cl‐ Ringer, diethylcarbamazine (10−4 to 2 × 10−3m) reversibly antagonized the voltage‐sensitive outward current of the bag. This effect was mimicked by high‐K+ Ringer or perfusion with 4‐aminopyridine (10−3 to 2 × 10−3 m). It was concluded that diethylcarbamazine did not react with the GABA receptor but antagonized a voltage‐sensitive K+ conductance.
STIMULATION OF ARACHIDONIC ACID METABOLISM AND GENERATION OF THROMBOXANE A2 BY LEUKOTRIENES B4, C4 AND D4 IN GUINEA‐PIG LUNG in vitro
Authors: PIPER PRISCILLA J. , SAMHOUN MARWA N. 
Published: July 2012

Leukotriene C4 (LTC4), LTD4, slow‐reacting substance of anaphylaxis (SRS‐A) (from guinea‐pig lung), bradykinin (Bk) and arachidonic acid (AA) release thromboxane A2 (TxA2) and prostaglandin‐like materials from guinea‐pig isolated perfused lungs.
Release of TxA2 induced by LTC4 and LTD4 is inhibited by a thromboxane synthetase inhibitor, imidazole (2.9 mm).
Mepacrine (200 μm), a phospholipase inhibitor, inhibits release of TxA2 and prostaglandin‐like materials caused by SRS‐A and Bk but not that due to exogenous AA
Leukotrienes B4, C4 and D4 are approximately equipotent in inducing dose‐related contractions of guinea‐pig parenchymal strips (GPPs).
Leukotriene‐induced contractions of GPPs are greatly inhibited by imidazole (2.9 mm), carbox‐yheptylimidazole (24 μm) and mepacrine (400 μm).
FPL 55712 (1.9 μm), the SRS‐A antagonist, blocks contractions of GPPs induced by LTC4 and LTD4 but not those due to LTB4 or Bk.
Tachyphylaxis to LTB4 occurs in GPPs but not to LTC4 or LTD4.
These results suggest that in guinea‐pig lung in vitro, LTB4, LTC4 and LTD4 activate a phospholipase with subsequent generation of cyclo‐oxygenase products of which TxA2 plays an important role.
FAST DESENSITIZATION OF THE NICOTINIC RECEPTOR AT THE MOUSE NEUROMUSCULAR JUNCTION
Authors: PENNEFATHER P. , QUASTEL D.M.J. 
Published: July 2012

When low concentrations of carbachol (2–20 μm) were applied by local superfusion to mouse diaphragm endplates, there occurred a rapid decrease (within seconds) in the height of miniature endplate currents (m.e.p.cs) in addition to the increase of muscle membrane conductance.
With 2, 5, 10 and 20 μm carbachol, m.e.p.c. heights were diminished by 5, 10, 30 and 50% respectively. A subsequent slow decrease in height took place at a rate corresponding to that reported for the slow desensitization produced by bath‐applied carbachol (see Adams, 1975).
The effect of carbachol on m.e.p.c. height was not affected by poisoning of acetylcholinesterase (AChE). After poisoning of AChE, 4 μm acetylcholine (ACh) depressed m.e.p.c. height by 23%.
At 20 μm carbachol, both the onset and offset of the effect on m.e.p.c. height lagged behind the subsynaptic conductance change, and the calculated change of subsynaptic agonist concentration, by about 3 s; the onset rate was at least ten times faster than expected for slow desensitization.
When the conductance responses produced by carbachol were corrected for fast desensitization, the slope of the log‐response log‐dose line (Hill coefficient) was increased from 1.7 to 2.0.
The Hill coefficient for fast desensitization was 1.4. The data were compatible with a cyclic model for fast desensitization, with receptor activation not a prerequisite for desensitization of receptors.
The failure of AChE poisoning to affect m.e.p.c. height during desensitization suggests that desensitized receptor associated with exogenous agonist can continue to bind quantal ACh.
THE EFFECT OF CHLORPROMAZINE, METYRAPONE, IMIPRAMINE AND SKF 525‐A ON THE HEPATIC FIRST PASS ELIMINATION OF PROPRANOLOL IN THE PITHED RAT
Authors: BARBER H.E. , KITTERINGHAM N.R. , PETRIE J.C. 
Published: July 2012

The effect of chlorpromazine, metyrapone, imipramine and SKF 525‐A on the hepatic first pass elimination of propranolol has been studied in the pithed rat.
The effect of chlorpromazine, metyrapone, imipramine and SKF 525‐A on the inhibition caused by propranolol of an elicited electrically induced tachycardia has also been studied.
The hepatic first pass elimination of propranolol was reduced following pretreatment with chlorpromazine, imipramine and SKF 525‐A but was not affected by pretreatment with metyrapone.
Chlorpromazine, imipramine and SKF 525‐A all resulted in an increased propranolol blood concentration after hepatic portal vein administration which was associated with decreased formation of metabolites and an enhanced inhibition of an electrically induced tachycardia.
EFFECTS OF 3, 4‐DIHYDRO‐8‐(2‐HYDROXY‐3‐ISOPROPYLAMINOPROPOXY)‐3‐NITROXY‐2H‐1‐BENZOPYRAN (K‐351) ON SMOOTH MUSCLE CELLS AND NEUROMUSCULAR TRANSMISSION IN THE CANINE MESENTERIC ARTERY
Authors: KOU KATSUHIRO , KURIYAMA HIROSI , SUZUKI HIKARU 
Published: July 2012

The effects of K‐351 on the electrical and mechanical responses were investigated in the canine mesenteric artery by isometric tension recording and the use of intracellular microelectrodes. The results were compared to the responses observed with other α‐adrenoceptor blocking agents.
K‐351 (> 3 × 10−7m) consistently inhibited the contraction evoked by perivascular nerve stimulation; however, K‐351 had no effect on the contraction evoked by direct muscle stimulation, after pretreatment with 3 × 10−7m tetrodotoxin.
Phentolamine enhanced and prazosin had no effect on the amplitude of contraction evoked by perivascular nerve stimulation at a high frequency (over 1.0 Hz). Pretreatment with phentolamine inhibited the contraction evoked by lower frequencies of perivascular nerve stimulation (below 0.5 Hz).
The potency for the inhibition of the response to perivascular nerve stimulation was in the order of K‐351 > phentolamine > prazosin, while the contractions induced by exogenously applied noradrenaline (5 × 10−7m) were inhibited in the order: prazosin > phentolamine > K‐351.
K‐351 (< 3 × 10−5m) did not modify the resting membrane potential or the membrane resistance, as estimated from the change in the amplitude of electrotonic potentials in the smooth muscle cell membranes.
K‐351 (> 3 × 10−7m) inhibited the amplitude of the first e.j.p. and e.j.ps after completion of the facilitation process following stimulation at frequencies over 0.25 Hz.
K‐351 (< 3 × 10−5m) did not modify the compound action potentials recorded from peripheral nerve bundles distributed on the mesenteric artery.
Phentolamine (> 1 × 10−8 m) inhibited the first e.j.p. but this agent either inhibited or enhanced the amplitude of e.j.p. after completion of the facilitation process produced by repetitive stimulation below or over 1.0 Hz stimulus frequencies, respectively. Prazosin (1 × 10−6m) had no effect on e.j.ps evoked by perivascular nerve stimulation, at any stimulus frequency applied.
These results indicate that K‐351 inhibits the extra‐junctional adrenoceptor with a slightly weaker potency than prazosin or phentolamine, but that this agent has a potent action as an intra‐junctional adrenoceptor blocking agent. Phentolamine acts mainly on the extra‐junctional adrenoceptors and also has weak actions on intra‐junctional adrenoceptors, as a blocking agent. This agent also inhibits the presynaptic α2‐adrenoceptor. Prazosin inhibits only the extra‐junctional α1‐adrenoceptor.
α2‐Adrenoceptor agonists induce mydriasis in the rat by an action within the central nervous system
Authors: Berridge T.L. , Gadie B. , Roach A.G. , Tulloch I.F. 
Published: July 2012

The effects of intravenous administration of the selective α2‐adrenoceptor agonists clonidine, UK 14,304 and guanoxabenz on rat pupil diameter were investigated.
In rats anaesthetized with pentobarbitone, each agonist produced a marked dose‐related increase in pupil diameter; the rank order of potency was: clonidine > UK 14,304 > guanoxabenz.
Pretreatment with the selective α2‐adrenoceptor antagonist, RX 781094 (0.5 mg/kg, i.v.), produced a parallel 30–40 fold shift to the right of the dose‐pupil dilator response curves for the three agonists. Yohimbine (1.5 mg/kg, i.v.) produced about a 10 fold rightward shift of the dose‐response curve for guanoxabenz. In contrast, the α1‐selective antagonist, prazosin (0.5 mg/kg, i.v.), failed to affect the dose‐response relation for guanoxabenz.
Several antagonists of varying selectivities towards α1‐ and α2‐adrenoceptors were tested for their ability to reverse the maximal mydriasis induced by guanoxabenz (0.3 mg/kg, i.v.). The rank order of potency of the antagonists producing a 50% reversal of this effect was: RX 781094 > yohimbine > piperoxan = rauwolscine > mianserin > RS 21361. Neither corynanthine nor prazosin reversed the guanoxabenz‐induced mydriasis.
Topical application of RX 781094 (0.1 to 3% w/v solutions) onto one eye produced a slow reversal of guanoxabenz‐induced mydriasis; the time course and degree of reversal were virtually the same in both eyes.
Intracerebroventricular administration of RX 781094 (1.25–15 μg total dose) caused a rapid dose‐related reversal of the maximal mydriasis induced by guanoxabenz (0.3 mg/kg, i.v.).
Guanoxabenz (0.3 and 1.0 mg/kg, i.v.) did not produce any dilation of the physostigmine‐constricted undamaged pupil of the pithed rat. Intravenous adrenaline was found to produce a small mydriatic effect, while atropine completely antagonized the effects of physostigmine in this preparation.
These results indicate that α2‐adrenoceptor agonists induce mydriasis in the rat through a central α2‐adrenoceptor mechanism. However, the site of action within the central nervous system remains to be determined.
Experimental conditions required for the enhancement by α‐adrenoceptor antagonists of noradrenaline release in the rabbit ear artery
Authors: Auch‐Schwelk Wolfgang , Starke Klaus , Steppeler Anton 
Published: July 2012

Segments of the rabbit ear artery were preincubated with (—)‐[3H]‐noradrenaline and then perfused/superfused and stimulated by transmural electrical pulses. The outflow of [3H]‐noradrenaline, separated from its metabolites by column chromatography, was determined.
Tetrodotoxin abolished, cocaine increased, and clonidine reduced the overflow of [3H]‐noradrenaline elicited by 10 shocks at 0.2 Hz, 10 shocks at 2 Hz or 100 shocks at 2 Hz.
The effects of yohimbine (0.1 or μm), phentolamine (1 μm) and piperoxan (1 or 10 μm) depended on the stimulation conditions. No antagonist increased the overflow of [3H]‐noradrenaline evoked by 10 pulses at 0.2 Hz, but all markedly increased the overflow evoked by 100 pulses at 2 Hz. Only piperoxan (10 μm) slightly enhanced the overflow at 10 pulses, 2 Hz. The effects of yohimbine and piperoxan were similar in arteries not exposed to cocaine and in those that were perfused/superfused with medium containing cocaine (10 μm) after preincubation.
It is concluded that yohimbine, phentolamine and piperoxan increase the release of noradrenaline only when the concentration of noradrenaline in the biophase of the ear artery is sufficiently high. The effect is, hence, an anti‐noradrenaline effect and due to the blockade of presynaptic α‐adrenoceptors. A second prerequisite for the release‐enhancing effect appears to be a sufficient length of the pulse train, indicating that the α‐adrenergic auto‐inhibition develops relatively slowly.