bluuebunny/crossref_metadata_2025_split huggingface dataset:
MECHANISM OF HISTAMINE RELEASE FROM RAT MAST CELLS INDUCED BY THE IONOPHORE A23187: EFFECTS OF CALCIUM AND TEMPERATURE
Authors: JOHANSEN TORBEN 
Published: July 2012

The mechanism of histamine release from a pure population of rat mast cells induced by the lipid soluble antibiotic, A23187, has been studied and compared with data for anaphylactic histamine release reported in the literature.
Histamine release induced by A23187 in the presence of calcium 10−3 mol/1 was completed in 10 minutes. By preincubation of the mast cells with A23187 for lOmin in the absence of calcium the histamine release induced by calcium, 10−3 mol/1 or 5 × 10−3 mol/1, was completed in 90s and 45 s, respectively.
A23187‐induced histamine release was maximal with calcium 10−3 mol/1 when the cells were incubated at 33 to 39°C for 10 minutes.
The cellular mechanism, which was stimulated by A23187 and calcium for the release of histamine, was irreversibly inactivated by incubation at 45°C.
An inhibition of energy metabolism was excluded as the cause of the heat inactivation.
The dependence of A23187‐induced histamine release on calcium and temperature, the time course of histamine release and the heat inactivation are consistent with the view that the same mechanism is involved in A23187‐induced and anaphylactic histamine release.
RELEASE OF 3H‐PURINES FROM [3H]‐ADENINE LABELLED RABBIT KIDNEY FOLLOWING SYMPATHETIC NERVE STIMULATION, AND ITS INHIBITION BY α‐ADRENOCEPTOR BLOCKADE
Authors: FREDHOLM BERTIL B. , HEDQVIST PER 
Published: July 2012

Rabbit kidneys were isolated and perfused with Tyrode solution. Release of 3H‐purines was studied after labelling of the adenine‐nucleotide stores with [3H]adenine (more than 60% uptake during a single passage).
One hour after labelling the spontaneous 3H‐outflow amounted to 0.1 to 0.2% of the total tissue content per minute. The release rate was enhanced following nerve stimulation (3 to 10 Hz), or brief infusion of noradrenaline (0.1 to 2.4 μg i.a.). Release of radioactivity was also enhanced by angiotensin II, by interruption of perfusion flow for 0.5 to 2 min and by hypoxia (5 to 25% 02).
The release of tracer induced by nerve stimulation or noradrenaline was markedly reduced or abolished by phenoxybenzamine, which also inhibited the vasoconstrictor response. The release following angiotensin II, ischaemia and hypoxia could not be antagonized by this α‐adrenoceptor antagonist.
The radioactivity in the kidney was predominantly in nucleotide form, while that released was N composed mainly of nucleosides, of which adenosine predominated.
The results indicate that in the rabbit kidney vasocontriction, arterial clamping or reduced perfusion oxygen tension, cause release of adenosine and related compounds. In view of the reported actions of adenosine on noradrenaline effects and release in the kidney a possible physiological role is discussed.
THE EFFECT OF ALKALINE EARTH CATIONS ON THE RELEASE OF HISTAMINE FROM RAT PERITONEAL MAST CELLS TREATED WITH COMPOUND 48/80 AND PEPTIDE 401
Authors: ATKINSON GORDON , ENNIS MADELEINE , PEARCE FREDERICK L. 
Published: July 2012

Extracellular calcium ions have a dual effect on the release of histamine from rat peritoneal mast cells treated with compound 48/80 and peptide 401. The release is either potentiated or inhibited according to the relative concentrations of ion and inducer.
Strontium similarly potentiates the release produced by optimal concentrations of inducer but higher concentrations are required than in the case of calcium. Strontium is markedly less inhibitory than calcium.
Mast cells may be depleted of intracellular calcium by incubation for short periods with the chelating agent, ethylenediamine tetraacetic acid (EDTA). They thereby become unresponsive to compound 48/80 and peptide 401 unless calcium is reintroduced into the incubation medium. Strontium and barium, but not magnesium, will substitute for calcium in this system. Barium additionally produces a marked release of histamine even in the absence of inducer. Pretreatment with the ionophore A23187 similarly inhibits the subsequent response to peptide 401 in divalent cation‐free medium. This inhibition is reversed on the reintroduction of calcium.
Compound 48/80 and peptide 401 release histamine from mast cells incubated in isotonic sucrose in the complete absence of added metal ions. However, the corrected release under these conditions is potentiated by both mono and divalent cations.
On the basis of these results, the possible mechanism of action of the basic releasing agents and their usefulness as models for studying histamine secretion is discussed.
THE EFFECTS OF HISTAMINE ON RESPONSES OF THE RABBIT EAR ARTERY TO ELECTRICAL STIMULATION AND TO EXOGENOUS NORADRENALINE
Authors: FOLDES A. , HALL R.C. 
Published: July 2012

The effects of a subconstrictor dose of histamine (9 × 10−7 mol/l) on the responses of the isolated perfused ear artery of the rabbit to electrical stimulation (E.S.) and to exogenous noradrenaline (NA) were investigated.
Both intraluminal (I/L) and extraluminal (E/L) histamine potentiated responses to E.S. and to I/L NA to the same extent.
Mepyramine alone (2.5 × 10−6 mol/l) had no effect on the response of the ear artery to either stimulus, but in the presence of this concentration of mepyramine, the potentiation by histamine of the response to I/L NA was significantly decreased and that to E.S. was replaced by inhibition.
The H1‐receptor agonist, 2(2‐pyridyl) ethylamine, applied I/L potentiated responses to I/L NA at both concentrations used (5.1 and 51 × 10−7 mol/l), but only potentiated the effects of E.S. at the higher concentration.
The H2‐receptor antagonist, metiamide (4 × 10−6mol/l), alone did not alter the extent of potentiation of responses to either E.S. or I/L NA by histamine. This suggests relatively weak H2‐receptor activity in the rabbit ear artery. In the presence, but not the absence of metiamide, the potentiation by histamine of the I/L NA response was reversible, an observation suggesting an interaction between metiamide and the non‐reversible component of the potentiating effect of histamine.
These results are interpreted in terms of postsynaptic H1‐receptors which potentiate and presynaptic H2‐receptors which inhibit contractile responses in the ear artery.
THE EFFECTS OF ISOPRENALINE AND BRADYKININ ON CAPILLARY FILTRATION IN THE CAT SMALL INTESTINE
Authors: GRANGER D.N. , RICHARDSON P.D.I. , TAYLOR A.E. 
Published: July 2012

Lymph flow, and both lymph and plasma protein concentrations were measured in isolated, blood‐perfused loops of cat ileum.
Permeability‐surface area (PS) products and the osmotic reflection coefficient (σ) of the intestinal capillaries were calculated.
Isoprenaline (one dose) or bradykinin (two different doses) was infused into the superior mesenteric artery.
Isoprenaline (blood concentration about 50 ng/ml) did not affect PS or σ.
Bradykinin (about 36 ng/ml) increased PS but as σ was unaltered, this was primarily due to an increased capillary surface area.
Bradykinin (about 680 ng/ml) increased PS and as σ was reduced, there was an increased capillary permeability.
Reasons for the lack of effect of isoprenaline at concentrations which increase capillary filtration coefficient are discussed.
These data show that this technique separates drug effects on capillary surface area from effects on capillary permeability.
AN EXAMINATION OF THE NEGATIVE FEEDBACK FUNCTION OF PRESYNAPTIC ADRENOCEPTORS IN A VASCULAR TISSUE
Authors: CHAN CHI‐CHUNG , KALSNER STANLEY 
Published: July 2012

The hypothesis was examined that presynaptic α‐adrenoceptors exert a negative feedback function regulating noradrenergic transmission.
Renal artery strips from cattle, pre‐incubated with [3H]‐noradrenaline, were stimulated with 300 pulses at 5 different frequencies, spanning the physiological range, and the efflux of tritium assessed both in the absence and presence of functional presynaptic receptors.
Considerable variation in the synaptic level of free and active noradrenaline with increasing frequency was apparent from the rates of development and the magnitudes of the mechanical responses but the overflow of tritium was constant at 1, 2, 10 and 15 Hz and slightly elevated at 5 Hz, providing no evidence for presynaptic modulation of release.
Phenoxybenzamine (3.3 × 10−5 m) enhanced the overflow of tritium most at the lowest frequency tested and to a similar extent at the other test frequencies, except 10 Hz where its effect was slightly reduced.
The conditions of the present experiments appeared optimal for the operation of the negative feedback system and the failure to observe an increased effectiveness of the antagonist with increasing frequency indicates that the physiological relevance of such a system is highly questionable and suggests that it may not function at all.
THE ACTIONS OF 5‐HYDROXYTRYPTAMINE AND HISTAMINE ON THE ISOLATED ILEUM OF THE TREE SHREW (Tupaia glis)
Authors: SAKAI K. , SHIRAKI Y. , TATSUMI T. , TSUJI K. 
Published: July 2012

Contractions to 5‐hydroxytryptamine (5‐HT) and histamine of longitudinal muscle from the isolated ileum of the tree shrew (Tupaia), guinea‐pig and rat were investigated by constructing dose‐response curves and studying the effects of various antagonists.
In the Tupaia and rat ileum the contraction to 5‐HT was reduced by methysergide but not affected by tetrodotoxin (TTX), morphine, hexamethonium (C6) or atropine. The response of guinea‐pig ileum to 5‐HT was not significantly inhibited by methysergide or C6, but was blocked by TTX, morphine and atropine.
Histamine‐induced contraction of Tupaia and guinea‐pig ileum was antagonized by diphenhydramine but not by TTX, morphine, C6 or atropine. Histamine was almost without effect on the rat ileum.
RELATIONSHIP BETWEEN INHIBITION OF ACETYLCHOLINESTERASE AND RESPONSE OF THE RAT PHRENIC NERVE‐DIAPHRAGM PREPARATION TO INDIRECT STIMULATION AT HIGHER FREQUENCIES
Authors: HEFFRON P.F. , HOBBIGER F. 
Published: July 2012

Rat isolated diaphragm preparations were stimulated indirectly either intermittently at 20, 50 or 100 Hz or continuously at 0.2 Hz.
Addition of 1.8 μm paraoxon (which inhibits acetylcholinesterase by forming a phosphorylated enzyme which undergoes slow spontaneous reactivation) for 5 min to the organ bath produced a failure of the muscle to maintain tetanic tension (tetanic fade, Wedensky inhibition) and potentiated the neuromuscular blocking activity of exogenous acetylcholine. The rates of recovery from both these effects were recorded.
In a series of experiments with dyflos (which inhibits acetylcholinesterase by forming a phosphorylated enzyme which does not undergo spontaneous reactivation) the relationship between functional acetylcholinesterase activity and neuromuscular blocking activity of exogenous acetylcholine was also determined.
From the data obtained, the relationship between functional acetylcholinesterase activity and tetanic fade was calculated. These calculations show that (i) a considerable reduction in functional acetylcholinesterase activity is required before the diaphragm loses its ability to respond with a sustained tetanus to indirect stimulation at higher frequencies, (ii) the minimum (critical) level of functional acetylcholinesterase activity required for a normal tetanic response is directly related to the frequency of stimulation and (iii) once functional acetylcholinesterase activity has been reduced to the critical level, a very small further reduction leads to a complete tetanic fade.
The meaning of functional acetylcholinesterase assays and of conclusions which can be drawn from them, is discussed.
RENIN‐ANGIOTENSIN MEDIATION OF ADRENAL CATECHOLAMINE SECRETION INDUCED BY HYPOGLYCAEMIA IN THE CAT
Authors: BUMPUS MERLIN F. , FEUERSTEIN GIORA , GUTMAN YEHUDA , KHOSLA MAHESH C. 
Published: July 2012

The mechanism involved in catecholamine (CA) release from the cat adrenal gland in response to insulin hypoglycaemia was studied. In intact cats, hypoglycaemia induced an 11 fold increase in adrenomedullary CA secretion.
Acute bilateral nephrectomy nearly abolished the increased CA release from the adrenal gland during hypoglycaemia.
Infusion of Sar1‐Ileu8‐Angiotensin II (AII), a competitive AII antagonist, suppressed the adrenomedullary response to the insulin‐induced hypoglycaemia. After termination of the antagonist infusion, CA secretion from the adrenal medulla increased rapidly, reaching the same level as in insulin‐treated cats.
Infusion of rabbit anti‐angiotensin I antibodies suppressed CA release from the adrenal gland of hypoglycaemic cats. This effect was more prolonged than that of Sar1‐Ileu8‐AII.
These results indicate that CA release from the adrenal medulla of the cat in response to insulin‐induced hypoglycaemia, is mediated through the renal reninangiotensin system. Since hypoglycaemia causes sympathetic stimulation through a central mechanism, angiotensin may act through the central nervous system.
MUSCARINIC RECEPTORS IN RAT SYMPATHETIC GANGLIA
Authors: BROWN D.A. , FATHERAZI S. , GARTHWAITE J. , WHITE R.D. 
Published: July 2012

Potential changes in isolated superior cervical ganglia of the rat produced by muscarinic‐receptor agonists were recorded by an extracellular ‘air‐gap’ method.
Muscarinic agonists produced a delayed low‐amplitude ganglion depolarization, frequently preceded by a hyperpolarization. Potentials were enhanced by reducing [K+]o or [Ca2+]o.
Mean ED50 values (μm) for depolarization at 25°C were: oxotremorine 0.004, methylfurmethide 0.11, (±)‐muscarine 0.24, furmethide 1.56, pilocarpine 4.81 and AHR‐602 (N‐benzylpyrrolidylacetate methobromide) 10.8. Responses produced by oxotremorine, pilocarpine and AHR‐602 showed some characteristics of ‘partial agonism’. ED50 values (μm) for choline esters (measured in the presence of 2.5 mm hexamethonium) were: acetylcholine 3.2, methacholine 59 and bethanechol 78.
Responses to muscarine were antagonized by hyoscine (K1 0.49 nm) atropine (K1 0.24 nm) methylscopolamine (K1 0.09 nm) lachesine (K1 0.15 nm) and (weakly) by hexamethonium (K1 0.2 mm). Propylbenzilylcholine mustard produced irreversible antagonism with an apparent onset rate constant of 2 times 105 m−1s−1.
Depolarization was accompanied by facilitation of submaximal ganglionic transmission.
Muscarine (1 to 100 μm) initially reduced, then increased, the rate of 86Rb+‐efflux from isolated ganglia at both 6 and 120 mm [K+]o. These effects were reduced by 1 μm hyoscine.
No consistent change in the amounts of cyclic 3′,5′‐guanosine monophosphate in isolated ganglia accompanying muscarinic depolarization could be detected.
Mean against ED50 values (μm) for contracting the rat isolated ileum were: oxotremorine 0.012, methylfurmethide 0.29, (±)‐muscarine 0.48, pilocarpine 7.8 and AHR‐602 9.9. Mean antagonist K1 values (nm) were: hyoscine 0.17, atropine 0.34 and lachesine 0.27.
It is concluded that ganglionic muscarinic receptors are quite similar to ileal receptors in terms of agonist ED50 and antagonist K1 values, and that the major difference between them lies in the greater ‘efficacy’ of certain agonists (pilocarpine, AHR‐602 and McN‐A‐343) on the ganglion.
THE EFFECT OF VERAPAMIL ON THE Ca2+‐TRANSPORTING AND Ca2+‐ATPase ACTIVITY OF ISOLATED CARDIAC SARCOLEMMAL PREPARATIONS
Authors: MAS‐OLIVA JAIME , NAYLER WINIFRED G. 
Published: July 2012

The effect of (±)‐, (+)‐ and (‐)‐verapamil on the Ca2+‐binding, Ca2+‐transporting activity, and Ca2+‐dependent adenosine triphosphatase (ATPase) activity of isolated cardiac sarcolemmal preparations was studied. Enzymatic treatment was used to establish the nature of the sites facilitating [14C]‐(±)‐verapamil binding.
(±)‐Verapamil 1 μm inhibited the passive binding of 45Ca2+. The (+)‐ and (‐)‐isomers were equiactive.
(±)‐Verapamil 1 μm inhibited the ATP‐dependent transport of 45Ca2+ and the associated activation of the Ca2+‐sensitive ATPase. The activity resided in the (‐)‐isomer.
Lineweaver‐Burk plots for the initial rates of ATP‐dependent transport showed that the inhibition induced by the (‐)‐isomer was accompanied by a reduced Km and Vmax.
Enzymatic removal of N‐acetyl neuraminic acid and galactose residues increased [14C]‐(±)‐verapamil binding; removal of N‐acetylglucosamine and treatment with phospholipase C and trypsin decreased the binding.
These results have been interpreted to mean that (‐)‐verapamil interferes with the ATP‐dependent Ca2+‐transporting properties of the sarcolemma, and that this effect is accompanied by an altered activity of the intrinsic Ca2+‐sensitive ATPase. N‐acetylneuraminic acid and galactose residues do not provide binding sites for verapamil at the cell surface.
DIPYRIDAMOLE: A POTENT STIMULATOR OF PROSTACYCLIN (PGI2) BIOSYNTHESIS
Authors: BLASS K.‐E. , BLOCK H.‐U. , FÖRSTER W. , PÖNICKE K. 
Published: July 2012

Dipyridamole (0.01 to 0.75 mm) increased prostacyclin (PGI2) biosynthesis from tritiated arachidonic acid in rat stomach fundus homogenates by 21 to 350%. The transformation of prostaglandin H2 (PGH2) to PGI2 by a microsomal fraction of pig aorta was stimulated by dipyridamole at 0.1 m by 63%
In the isolated perfused heart of the rabbit dipyridamole at 1 and 5 μg/ml increased PGI2 release by 70% and 146% respectively.
Our results show a stimulation of the second step in PGI2 biosynthesis (from endoperoxides) by dipyridamole. This effect should be considered in relation to the therapeutic usage of the drug in myocardial infarction.
CURARE‐LIKE EFFECT OF PROPRANOLOL ON RAT EXTRAOCULAR MUSCLES
Authors: CHIARANDINI D.J. 
Published: July 2012

The effects were studied of the β‐adrenoceptor blocking drug, (±)‐propranolol and its (+)‐ and (−)‐isomers on contractility of rat isolated diaphragm and inferior rectus muscles.
Propranolol (10−5 m) did not modify the resting tension nor the electrically‐induced twitch contraction in diaphragm and extraocular muscles, nor the tonic tension evoked in the latter by high K concentrations.
In inferior rectus preparations (±)‐propranolol (5 × 10−6 m) reduced significantly tensions evoked by succinylcholine (SCh). Cumulative dose‐response curves to SCh were shifted to the right in a nearly parallel manner by (+)‐ and (−)‐propranolol which were about equiactive.
It is concluded that the depressant action of propranolol is independent of its adrenoceptor blocking potency and it is not due to an alteration of the contraction mechanism. Propranolol appears to depress SCh‐evoked tensions through a curare‐like effect on cholinoceptors.
THE RESPONSE OF THE ISOLATED DUCTUS ARTERIOSUS TO TRANSMURAL STIMULATION AND DRUGS
Authors: BODACH E. , COCEANI F. , DUMBRILLE A. , OKPAKO D.T. , OLLEY P.M. 
Published: July 2012

Responses of isolated ductus arteriosus preparations from near term guinea‐pigs and lambs to transmural electrical stimulation and drugs were studied in a low oxygen medium (Po2 19 to 28 mmHg).
Acetylcholine and noradrenaline contracted both vessels in a dose‐dependent manner, their threshold being between 10−8 and 10−7 m. Transmural stimulation (pulse width 0.2 to 0.6 ms, typically 20 Hz) also contracted the vessels.
Atropine and phentolamine or dibenzyline selectively blocked responses to acetylcholine and noradrenaline, respectively.
In the guinea‐pig ductus, part of the response to transmural stimulation was due to activation of intrinsic adrenergic nerves since the responses were reduced by α‐adrenoceptor antagonists, bretylium or prior reserpine treatment, but not by atropine. The response of the lamb ductus to transmural stimulation varied greatly in magnitude and was inconsistently affected by α‐adrenoceptor blocking drugs.
There was no evidence that transmural stimulation activated cholinergic nerves in either species.
After inactivation of α‐adrenoceptors with dibenzyline, noradrenaline caused a β‐adrenoceptor‐mediated relaxation. Both this effect and isoprenaline‐mediated relaxation were blocked by propranolol. β‐Adrenoceptor activity was more prominent in the ductus of the guinea‐pig than of the lamb.
Raising the Po2 from 19–28 to 92–98 mmHg increased the response of the guinea‐pig ductus to transmural stimulation suggesting that, in this species, physiological elevation of oxygen tension at birth may increase transmitter release from intrinsic adrenergic nerves. Whether this mechanism would contribute to ductus closure remains an open question.
We postulate that β‐adrenoceptor‐mediated relaxation has a role in maintaining ductus patency in the guinea‐pig foetus.
A MAXIMUM CONTRACTION AND SUBSTANTIAL QUANTITIES OF TRITIUM CAN BE OBTAINED FROM TETRAETHYLAMMONIUMTREATED [3H]‐NORADRENALINE PRELOADED, RAT VAS DEFERENS IN RESPONSE TO A SINGLE ELECTRICAL SHOCK
Authors: WAKADE ARUN R. 
Published: July 2012

In the normal and phenoxybenzamine‐treated vasa deferentia of the rat the overflow of tritium after preloading with [3H]‐noradrenaline increased with the increase in frequency of transmural stimulation. Phenozybenzamine enhanced overflow by 5 to 7 fold.
After tetraethylammonium (TEA, 10 mm), fractional tritium overflow at 5 Hz increased from a control value of 2.8 to 53 × 10−4, and at 0.5 Hz it reached 154 × 10−4. Enhancement of overflow was inversely related to the frequency of stimulation.
Contractor responses of the vas deferens induced by transmural stimulation were markedly potentiated, both in amplitude and duration, by 10 mm TEA. The contraction developed in the presence of 10 mm TEA at 0.5 Hz was comparable to that obtained at 10 Hz in normal Krebs solution.
In the presence of 5 mm TEA, contractions of the vas deferens caused by exogenous noradrenaline were potentiated about 5 fold.
The overflow and contractor response induced by 45 mm K were enhanced about 5 fold in 10 mm TEA‐Krebs solution. Facilitation of K‐induced overflow by TEA was reduced over 50% by tetrodotoxin (TTX, 1 μm).
Delivery of a single shock (1.0 ms duration) to 10 mm TEA‐treated vas deferens resulted in a 63% increase in tritium overflow over background overflow. The fractional overflow amounted to almost 720 × 10−4 after a single shock, as compared to 154 × 10−4 obtained at 0.5 Hz.
The vas deferens treated with 10 mm TEA and stimulated by a single shock developed a contraction which was greater in amplitude and duration than that seen in normal tissue at 10 Hz.
Five second serial samples collected from superfused 10 mm TEA‐treated vas deferens contained maximum quantities of radioactivity in the first 5 s after a single shock. In subsequent samples, radioactivity gradually declined, and reached prestimulation level after about 25 s.
The fractional overflow caused by stimulation at 0.1 Hz in 10 mm TEA‐treated tissue progressively increased as external Ca was gradually raised from 0.83 to 10 mm.
The mechanism of action of TEA in enhancing the overflow of sympathetic transmitter, particularly in response to a single shock, is discussed in relation to Ca.