bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECT OF NEUROLEPTICS AND OTHER DRUGS ON MONOAMINE UPTAKE BY MEMBRANES OF ADRENAL CHROMAFFIN GRANULES
Authors: PLETSCHER A. 
Published: July 2012

The effects have been investigated of various reserpine‐like, neuroleptic, antidepressant and other compounds on the adenosine‐5′‐triphosphate (ATP)‐dependent uptake of noradrenaline (NA) (reserpine‐sensitive) and tryptamine (reserpine‐resistant) by membranes of isolated chromaffin granules of bovine adrenal medulla.
Reserpine and Ro 4–1284 (2‐hydroxy‐2‐ethyl‐3‐isobutyl‐9,10‐dimethoxy‐hexahydro‐11bH‐benzo(a)quinolizine) as well as neuroleptics (e.g. chlorpromazine and haloperidol) inhibited the NA uptake, but the reserpine‐like drugs were more potent. In contrast, Ro 4–1284 showed a considerably weaker effect than the neuroleptics in interfering with tryptamine uptake. Chlorpromazine had about the same potency in inhibiting NA and tryptamine uptake, whereas the action of haloperidol was more pronounced on the uptake of NA than of tryptamine.
The relative potencies of neuroleptic drugs in inhibiting NA uptake by granule membranes in vitro corresponded only partly to their relative potencies in enhancing dopamine turnover in vivo.
The inhibition of NA uptake by chlorpromazine and Ro 4–1284 appeared to be of the noncompetitive type.
Chlorpromazine did not influence the decrease in ATP induced by granule membranes in the incubation medium.
Other basic, but not acidic compounds also inhibited NA uptake by granule membranes; their potency was of the order of that of chlorpromazine (antidepressants) or weaker (e.g. benzodiazepines).
In conclusion, the mechanism of action of neuroleptics probably differs from that of reserpine‐like drugs in the inhibition of monoamine uptake by membranes of catecholamine storage organelles. While interference with the granular storage of dopamine at the granule membrane level may contribute to the in vivo action of neuroleptics (e.g. in enhancing dopamine turnover), additional effects of these drugs must be involved in vivo, e.g. blockade of pre‐ and postsynaptic dopamine receptors.
THE DEVELOPMENT OF TACHYPHYLAXIS TO ELECTRICAL STIMULATION IN GUINEA‐PIG ILEAL LONGITUDINAL MUSCLES AND THE POSSIBLE PARTICIPATION OF ADENOSINE AND ADENINE NUCLEOTIDES
Authors: HAYASHI E. , KUNITOMO M. , MORI M. , SHINOZUKA K. , YAMADA S. 
Published: July 2012

Electrically (30 Hz) induced contractions of guinea‐pig isolated ileal longitudinal muscles were reduced by tetrodotoxin (1 μm), atropine (1 μm), adenosine (30 μm) and morphine (10 μm).
When stimulated with 10 or 30 Hz for 10 s at 1 min intervals, a progressive decline of amplitude of the contraction was seen (development of tachyphylaxis). At this time, the contractile response to 1,1‐dimethyl‐4‐phenylpiperazinium iodide (DMPP) (10 μm) was also greatly reduced.
The smaller responses to electrical stimulation and DMPP during tachyphylaxis were restored to their initial amplitude by the addition of theophylline (10 μm). The appearance of tachyphylaxis was prevented by pretreatment with theophylline (1 to 10 μm) and was greatly accelerated by pretreat‐ment with dipyridamole (0.1, 1 μm).
In [14C]‐choline or [3H]‐adenosine preloaded muscle strips, electrical stimulation (30 Hz) increased the 14C‐ or 3H‐output, the effect being sensitive to tetrodotoxin blockade. The tachyphylaxis to electrical stimulation was accompanied by a considerable and sustained increase in 3H‐output, an effect that was accelerated by dipyridamole (1 μm). The 14C‐output initially increased but fell off gradually with the development of tachyphylaxis at which time theophylline (30 1) reversed the fall.
There was a marked increase in the proportion of released [3H]‐adenosine to its derivatives during the development of tachyphylaxis. Approximately 60% of the released total radioactivity after tachyphylaxis was found to be [3H]‐adenosine.
These results suggest that the development of tachyphylaxis may be closely associated with the release of endogenous adenosine derivatives (mostly adenosine) which have presynaptic inhibitory actions on the cholinergic elements in guinea‐pig ileum.
EFFECT OF LABETALOL ON THE UPTAKE OF [3H]‐(‐)‐NORADRENALINE INTO THE ISOLATED VAS DEFERENS OF THE RAT
Authors: DREW G.M. , HILDITCH A. , LEVY G.P. 
Published: July 2012

The effects of the combined a‐ and, B‐adrenoceptor blocking drug, labetalol, on the uptake of [3H]4‐)‐noradrenaline into the isolated vas deferens of the rat have been determined and compared with those of some other ca‐adrenoceptor blocking drugs and cocaine.
Labetalol, like cocaine, produced a simple competitive inhibition of [3H]‐(‐)‐noradrenaline uptake and was about 4 times less potent than cocaine. It is concluded that labetalol is a potent inhibitor of uptake1. Phentolamine and thymoxamine also inhibited [3H]‐(‐)‐noradrenaline uptake, and were respectively 8 and 14 times less potent than cocaine. Tolazoline, piperoxan and yohimbine were inactive in concentrations up to 30 ig/ml.
The uptake1 blocking action of labetalol could explain, at least in part, the previously reported difference in its ability to block noradrenaline and phenylephrine vasopressor responses in the anaesthetized dog.
The possibility that uptake1 inhibitory concentrations of labetalol could be present in the blood of subjects receiving normal antihypertensive doses of the drug is discussed.
THE EFFECTS OF DILTIAZEM (CRD‐401) ON THE MEMBRANE AND MECHANICAL PROPERTIES OF VASCULAR SMOOTH MUSCLES OF THE RABBIT
Authors: ITO YUSHI , KURIYAMA HIROSI , SUZUKI HIKARU 
Published: July 2012

The effects of diltiazem on electrical and mechanical properties of vascular smooth muscles of the rabbit were examined by various experimental procedures.
In the pulmonary artery, diltiazem (0.1 to 10 μg/ml) did not modify the membrane potential (‐56 mV), length constant of the tissue (1.47 mm) or rectifying properties of the membrane. Diltiazem (0.1 to 10 μg/ml) did not modify the membrane potential of the mesenteric artery (‐62.5 mV).
Diltiazem (1 to 10 μg/ml) suppressed mechanical responses of pulmonary and mesenteric arteries induced either by direct stimulation of the muscle (1.0 s pulse) or by neural activation (0.5 ms pulse, 30 Hz and 10 s total duration). Diltiazem suppressed the contraction induced by nerve stimulation to a greater extent than that induced by direct muscle stimulation.
When the depolarization‐contraction relationship of the smooth muscle of the pulmonary artery was observed by voltage clamp technique, diltiazem (1 to 10 μg/ml) raised the critical membrane potential to evoke contraction from 5 mV to 12 mV, and reduced the amplitude of contraction obtained at any given depolarization level.
In the pulmonary artery, diltiazem (10 μg/ml) suppressed K‐induced contraction and raised the mechanical threshold, while K‐induced depolarization was not suppressed. Diltiazem (1 to 10 μg/ml) also suppressed noradrenaline‐induced contraction, raised the mechanical threshold and suppressed noradrenaline‐induced depolarization.
The vasodilator actions of diltiazem on the vascular smooth muscle were compared to vasodilator actions observed with other Ca‐antagonists.
MODULATION OF NORADRENERGIC TRANSMISSION IN THE RABBIT EAR ARTERY BY DOPAMINE
Authors: HOPE WENDY , McCULLOCH MARIAN W. , RAND M.J. , STORY D.F. 
Published: July 2012

The effects of dopamine on vasoconstrictor responses to field stimulation of sympathetic nerves and to exogenous noradrenaline were studied in the isolated ear artery of the rabbit. Responses to sympathetic nerve stimulation were depressed, initially, by infusions of dopamine (0.5 to 1 μm), but the responses partially recovered in the continued presence of dopamine. Responses to noradrenaline were unchanged at the start of the dopamine infusions but were enhanced as the infusions continued and also after cessation of the infusion.
Dopamine (0.5 μm) reduced the stimulation‐induced efflux of tritium from segments of ear artery labelled with [3H]‐noradrenaline. The reduction persisted during 65 min of dopamine infusion, after which time the vasoconstrictor responses had generally recovered to 93% of control level. On ceasing the infusion, the stimulation‐induced efflux and the vasoconstrictor responses were enhanced.
Metoclopramide, haloperidol and ergometrine, each in a concentration of 0.2 μm, prevented the inhibitory effect of 0.5 μm dopamine on the stimulation‐induced tritium release, but not the inhibitory effect of 0.5 μm noradrenaline. Phenoxybenzamine (0.2 and 1 μm) and phentolamine (1 μm) prevented the inhibitory effects of both noradrenaline and dopamine on the stimulation‐induced efflux, and phentolamine (0.2 μm) prevented the inhibition of the stimulation‐induced release by noradrenaline but only partially prevented the inhibitory effect of dopamine on the stimulation‐induced efflux.
A possible rôle for dopamine in the modulation of noradrenergic transmission is suggested.
4‐AMINOPYRIDINE AND EVOKED TRANSMITTER RELEASE FROM MOTOR NERVE ENDINGS
Authors: ILLES P. , THESLEFF S. 
Published: July 2012

In the presence of tetrodotoxin, electrotonic depolarization of frog motor nerve terminals causes the appearance of stimulus‐graded endplate potentials. When 4‐aminopyridine is added, the graded endplate potential is converted into a triggered all‐or‐none response resulting in giant endplate potentials of about 70 mV amplitude and 50 ms duration. The triggered endplate potentials are abolished in Ca2+ ‐free saline and are blocked by Mn2+ ions. Sr2+ but not Ba2+ can replace Ca2+ in supporting transmitter release. Mg2+ fails, even in concentrations as high as 32 mm, to affect the amplitude and the shape of the endplate potential but abolishes it when the Ca2+ concentration is reduced to 0.2 mm.
Despite the large amplitude of the triggered endplate potential in the presence of 4‐aminopyridine and tetrodotoxin, repetitive stimulation up to 10 Hz causes only a small decline in amplitude of successive endplate potentials. However, in the presence of (+)‐tubocurarine or gallamine, repetitive nerve stimulation produces a marked decline in successive endplate potential amplitude. The fall is counteracted when evoked transmitter release is reduced in the presence of 0.2 mm Ca2+. The results suggest that in the presence of 4‐aminopyridine such large amounts of transmitter are released that even during repetitive stimulation (5 to 10 Hz) endplate potentials are of maximal amplitude.
4‐Aminopyridine causes a parallel shift to the right of the dose‐response curve to Mg2+ for blockade of nerve impw/se‐evoked transmitter release (in the absence of tetrodotoxin). A similar parallel shift occurs in the presence of tetraethylammonium and guanidine.
It is concluded that 4‐aminopyridine increases transmitter release by enhancing the transport efficacy for Ca2+ across the nerve terminal membrane during nerve terminal depolarization.
PRESYNAPTIC INHIBITORY ACTION OF 5‐HYDROXYTRYPTAMINE IN DOG ISOLATED SAPHENOUS VEIN
Authors: FENIUK W. , HUMPHREY P.P.A. , WATTS A.D. 
Published: July 2012

The effect of 5‐hydroxytryptamine on contractile responses to sympathetic nerve stimulation has been studied in the dog isolated saphenous vein.
Electrical stimulation (0.1 to 10 Hz) of dog saphenous vein strips produced frequency‐dependent contractions. Contractions produced by stimulation at 2 Hz were almost completely blocked by tetrodotoxin (3.1 × 10−8 mol/l) or phentolamine (5.0 × 10−6 mol/l) but mecamylamine (5.0 × 10−6 mol/l) had little effect. This suggests that the contractions were mediated predominantly through noradrenaline release from postganglionic noradrenergic nerves.
Contractions produced by intermittent electrical stimulation at 2 Hz were inhibited by 5‐hydroxytryptamine (1.0 × 10−9 to 1.0 × 10−7 mol/l) in a concentration‐dependent manner whilst contractions induced by exogenous noradrenaline were not affected.
The inhibitory action of 5‐hydroxytryptamine was most marked at low frequencies of stimulation and with low pulse numbers.
High external calcium concentrations (3.9 and 5.2 × 10−3 mol/l) reduced the inhibitory action of 5‐hydroxytryptamine.
Cyproheptadine (1.0 × 10−8 mol/l to 1.0 × 10−6 mol/l) or morphine (1.0 × 10−7 mol/l to 1.0 × 10−5 mol/l) did not antagonize the inhibitory action of 5‐hydroxytryptamine. Methysergide (1.0 × 10−7 mol/l) slightly reduced the contractions produced by electrical stimulation and only weakly antagonized the action of 5‐hydroxytryptamine.
It is suggested that a 5‐hydroxytryptamine receptor exists presynaptically in the dog isolated saphenous vein strip and that stimulation of this receptor by low concentrations of 5‐hydroxytryptamine inhibits the release of noradrenaline from noradrenergic nerves. This receptor type is resistant to blockade by ‘classical’ 5‐hydroxytryptamine antagonists.
EFFECTS OF CLONIDINE, PRAZOSIN AND PHENTOLAMINE ON HEART RATE AND CORONARY SINUS CATECHOLAMINE CONCENTRATION DURING CARDIOACCELERATOR NERVE STIMULATION IN SPINAL DOGS
Authors: CAVERO I. , DENNIS T. , LEFÈVRE‐BORG FRANÇOISE , PERROT P. , ROACH A.G. , SCATTON B. 
Published: July 2012

In spinal dogs, continuous electrical stimulation of the cardioaccelerator nerve produced a transient rise in aortic blood pressure and a sustained increase in both heart rate and coronary sinus blood flow. The latter effects were accompanied by a significant elevation in the coronary sinus plasma noradrenaline concentration without significant changes in the levels of dopamine and adrenaline. The concentrations of the three catecholamines in thoracic aorta plasma were not significantly changed by cardioaccelerator nerve stimulation.
Clonidine (20 μg/kg, i.v.), given during cardioaccelerator nerve stimulation, increased both mean aortic blood pressure and coronary sinus blood flow and decreased heart rate and coronary sinus venous plasma noradrenaline overflow.
Phentolamine (0.3 mg/kg, i.v.) completely antagonized these effects of clonidine. Prazosin (0.3 mg/kg, i.v.) inhibited by only 43 and 38% the respective reductions in heart rate and noradrenaline overflow elicited by clonidine.
On termination of cardioaccelerator stimulation (about 10 min after either prazosin or phentolamine), heart rate and coronary sinus noradrenaline overflow returned to control prestimulation levels.
Phentolamine or prazosin, administered alone during stimulation of the cardioaccelerator nerve, increased heart rate and noradrenaline overflow into the coronary sinus plasma. However, intravenous phentolamine and prazosin, in contrast to desipramine (0.3 mg/kg, i.v.) or tyramine (1.0 mg, i.a.), failed to change the tachycardia resulting from the local administration of noradrenaline into the sinus node artery (i.a.).
These results show that in spinal dogs the clonidine‐induced reduction in heart rate (elevated by electrical stimulation of the cardioaccelerator nerve) is accompanied by a fall in the quantity of noradrenaline overflowing into the coronary sinus plasma. The latter effect is presumably the result of an action of clonidine on cardiac presynaptic α‐adrenoceptors, the activation of which is followed by a reduction in the release of noradrenaline per nerve impulse. Phentolamine and prazosin are both antagonists of cardiac presynaptic α‐adrenoceptors in spinal dogs, as suggested by their action against clonidine and by their positive chronotropic effect when administered during stimulation of the cardioaccelerator nerve.
EVIDENCE FOR AN ENDOGENOUS DOPAMINE‐MEDIATED HYPOTHERMIA IN THE RAT
Authors: COX B. , LEE T.F. 
Published: July 2012

Unilateral intrahypothalamic injection of either dopamine (10 μg) or amphetamine (10 μg) caused a fall in core temperature in the rat. Pimozide (0.5 mg/kg, i.p.) significantly reduced the hypothermic response, whereas pretreatment with phentolamine (1 mg/kg, i.p.) or methysergide (5 mg/kg, i.p.) was ineffective.
Systemic pretreatment with cocaine (20 mg/kg) abolished the hypothermic effect of amphetamine, but slightly enhanced the hypothermic response to dopamine.
Systemic pretreatment with tranylcypromine (10 mg/kg) had no significant effect on the fall in core temperature induced by either amphetamine or dopamine.
Intraperitoneal injection of cocaine and tranylcypromine, on their own, caused a fall in core temperature in the rat, which was significantly antagonized by either systemic or central pretreatment with pimozide. Phentolamine and methysergide failed to block the hypothermia.
Unilateral intrahypothalamic injection of cocaine (20 μg) or tranylcypromine (10 μg) also caused a significant fall in core temperature, which was reduced by intrahypothalamic pretreatment with pimozide (0.5 μg), but not significantly changed by pretreatment with phentolamine (25 μg) or methysergide (5 μg).
These results provide evidence for the presence of a dopaminergic system within the preoptic region, which mediates a lowering of core temperature in the rat.
A COMPARISON OF THE FACILITATORY ACTIONS OF 4‐AMINOPYRI‐DINE METHIODIDE AND 4‐AMINOPYRIDINE ON NEUROMUSCULAR TRANSMISSION
Authors: HORN A.S. , LAMBERT J.J. , MARSHALL I.G. 
Published: July 2012

4‐Aminopyridine methiodide (4‐APMI), a quaternary analogue of aminopyridine (4‐AP), was tested for neuromuscular facilitatory actions on the chick biventer cervicis and frog sartorius nerve‐muscle preparations.
In the chick, 4‐APMI (10−4 to 10−2m) augmented indirectly elicited twitches and reversed tubocurarine‐induced neuromuscular block. Reversal of tubocurarine block was observed after treatment of the muscle with an anticholinesterase. 4‐APMI did not itself produce contracture but augmented responses to added acetylcholine.
4‐APMI (10−4m) prolonged the time courses of endplate potentials (e.p.ps) and miniature end‐plate potentials (m.e.p.ps) in the frog.
4‐APMI (10−4m) increased e.p.p. quantal content. 4‐AP was about 100 times more active than 4‐APMI in increasing quantal content. Both compounds prolonged muscle action potentials at similar concentrations.
4‐APMI (10−3 to 3 × 10−3m) possessed anticholinesterase activity in homogenates of chick biventer cervicis muscle.
It is concluded that 4‐APMI increases evoked acetylcholine release and also possesses a weak anticholinesterase action. The greater action of 4‐AP on quantal content is probably due to an intracellular action, possibly involving the release of calcium ions.
EXOCYTOTIC RELEASE OF CATECHOLAMINES AND DOPAMINE‐β‐HYDROXYLASE FROM THE PERFUSED ADRENAL GLAND OF THE RABBIT AND CAT
Authors: SORIMACHI MASARU , YOSHIDA KENICHI 
Published: July 2012

Secretion of catecholamines (CA) and dopamines‐hydroxylase (DBH) activity from the perfused rabbit and cat adrenal gland was studied following stimulation by a number of substances, including the physiological transmitter, acetylcholine (ACh), added to the perfusion fluid.
Stimulation caused a proportional secretion of DBH and CA from the untreated rabbit adrenal. The ratio of DBH/CA was 11.2 + 0.9 (mean + s.e.) which was close to that found in the crude granule fraction of the contralateral gland (11.4 ± 0.7).
After treatment with insulin (40 u/kg) for 3 h or with reserpine (0.25 mg/kg) for 24 h, CA and DBH contents decreased in a parallel fashion in the granule fraction, thus resulting in a similar ratio of DBH/CA in the gland. The ratio in the effluents after stimulation was similar to that found in the untreated gland.
Higher doses of reserpine (0.7 to 2.5 mg/kg) increased the ratio of DBH/CA in the granule fraction and was dependent on the doses employed. The ratio in the effluents from these glands after stimulation paralleled these increased values.
Concomitant secretion of CA and DBH in response to stimulation was also observed in the perfused cat adrenal. However, the ratio of DBH/CA in the effluents tended to be lower than that found in the granule fraction.
These results support the concept of exocytotic secretion of CA in the adrenal medulla.
STUDIES ON THE MECHANISM OF ACTION OF GLUCAGON IN STRIPS OF RABBIT RENAL ARTERY
Authors: GAGNON G. , REGOLI D. , RIOUX F. 
Published: July 2012

The vasodilator effects of glucagon and adenosine cyclic 3′,5′‐monophosphate (cyclic AMP) were evaluated in strips of rabbit renal artery contracted with noradrenaline (NA) in the absence and presence of phosphodiesterase inhibitors or calcium (Ca2+) antagonists.
The vascular relaxant effect of glucagon was markedly potentiated by various concentrations of four different phosphodiesterase inhibitors (papaverine, theophylline, 3‐isobutyl‐1‐methylxanthine (IBMX) and indomethacin), while that of cyclic AMP was potentiated by only two of them (papaverine and indomethacin) and inhibited by the others (theophylline and IBMX).
Amongst the four phosphodiesterase inhibitors, IBMX (10 μg/ml) was found to produce the largest potentiation (e.g. the sensitivity increased by a factor of 10) of glucagon‐induced vascular relaxations (ED50 of glucagon in the presence of IBMX = 9.2 ± 1.0 ng/ml).
Ca2+ antagonists such as verapamil and SKF 525A produced a dose‐dependent inhibition of the vasodilator action of glucagon. Verapamil (2.5 μg/ml) also antagonized cyclic AMP‐induced vascular relaxations.
The vasodilator effect of verapamil was inhibited dose‐dependently by raising the concentration of extracellular Ca2+ from 0.05 to 0.2 g/l (or 1.25 to 5.0 mm) while those elicited by glucagon or cyclic AMP were not influenced, thus suggesting that the latter two drugs do not interfere with Ca2+ influx.
Disodium edetate (Na2EDTA, 210 to 840 μg/l) produced a dose‐dependent vasodilator effect which was attributed to the facilitation of Ca2+ extrusion from the smooth muscle cells and/or Ca2+ binding to the cell membrane. The relaxation produced by Na2EDTA was significantly blocked by verapamil (10 μg/ml) or SKF 525A (10 μg/ml).
The results were taken as an indication that glucagon produces at least a fraction of its vasodilator effect by promoting Ca2+ extrusion from the vascular smooth muscle cells and/or Ca2+ binding to or sequestration into intracellular sites, presumably via a cyclic AMP‐dependent mechanism.
ANTIGEN‐INDUCED BRONCHIAL ANAPHYLAXIS IN ACTIVELY SENSITIZED GUINEA‐PIGS: ANTI‐ANAPHYLACTIC EFFECTS OF SODIUM CROMOGLYCATE AND AMINOPHYLLINE
Authors: ANDERSSON PER 
Published: July 2012

The inhibitory effects of sodium cromoglycate (SCG) and aminophylline on antigen‐induced bronchial anaphylaxis in guinea‐pigs, actively sensitized according to different regimens, were examined.
SCG (1 mg/kg administered intravenously) reduced the anaphylactic response in animals sensitized with 1 μg ovalbumin (OA) together with Al(OH)3 100 mg, and challenged at 14 and 40 days after sensitization. If higher doses of antigen (10 μg OA together with Al (OH)3 or 5 mg OA on day 0 plus 10 mg OA on day 2) were used for sensitization, the protective effect of SCG was found only in animals tested 14 days after sensitization.
A low dose of aminophylline (0.3 mg/kg) that was without a direct bronchodilator effect when tested against a histamine (4 μg/kg)‐induced bronchospasm, produced an anti‐anaphylactic effect. The anti‐anaphylactic effect of aminophylline varied slightly with the way the animals were immunized and the time at which they were tested.
It is concluded that bronchial anaphylaxis in guinea‐pigs sensitized with low doses of ovalbumin is a suitable model for the evaluation of anti‐anaphylactic properties of drugs.