bluuebunny/crossref_metadata_2025_split huggingface dataset:
PHARMACOLOGICAL CHARACTERIZATION OF THE PRESYNAPTIC α‐ADRENOCEPTORS REGULATING CHOLINERGIC ACTIVITY IN THE GUINEA‐PIG ILEUM
Authors: DREW G.M. 
Published: July 2012

The presynaptic α‐adrenoceptors located on the terminals of the cholinergic nerves of the guinea‐pig myenteric plexus have been characterized according to their sensitivities to α‐adrenoceptor agonists and antagonists.
Electrical stimulation of the cholinergic nerves supplying the longitudinal muscle of the guinea‐pig ileum caused a twitch response. Clonidine caused a concentration‐dependent inhibition of the twitch response; the maximum inhibition obtained was 80 to 95% of the twitch response. Oxymetazoline and xylazine were qualitatively similar to clonidine but were about 5 times less potent. Phenylephrine and methoxamine also inhibited the twitch response but were at least 10,000 times less potent than clonidine.
The twitch‐inhibitory effects of clonidine, oxymetazoline and xylazine, but not those of phenylephrine or methoxamine, were reversed by piperoxan (0.3 to 1.0 μg/ml).
Lysergic acid diethylamide (LSD) inhibited the twitch response, but also increased the basal tone of the ileum. Mepyramine prevented the increase in tone but did not affect the inhibitory action of LSD. Piperoxan or phentolamine only partially antagonized the inhibitory effect of LSD.
Phentolamine, yohimbine, piperoxan and tolazoline were potent, competitive antagonists of the inhibitory effect of clonidine with pA2 values of 8.51, 7.78, 7.64 and 6.57 respectively.
Thymoxamine was a weak antagonist of clonidine; it also antagonized the twitch‐inhibitory effect of morphine. Thus, its effect against clonidine is probably not mediated specifically at presynaptic α‐adrenoceptors.
Labetalol, itself, depressed the twitch response but did not antagonize the inhibitory effect of clonidine on the residual twitch.
The results demonstrate that the presynaptic α‐adrenoceptors in the guinea‐pig ileum are of the same type as those located presynaptically in sympathetically innervated tissues. They are a2‐adrenoceptors and are different from those located postsynaptically.
INHIBITION BY N‐ACETYL NEURAMINIC ACID OF PLATELET THROMBOGENESIS INDUCED BY LASER INJURY TO RAT AND HAMSTER VENULES
Authors: BORN GUSTAV V.R. , KOVACS IREN B. 
Published: July 2012

In rats and hamsters under barbiturate anaesthesia, laser radiation to venules about 50 μm in diameter in mesoappendix and cheek pouch respectively caused the formation of platelet thrombi which occluded the vessels in about 9 min.
This occlusion time was significantly prolonged by the intravenous injection of N‐acetyl neuraminic acid (NANA) but not by D‐glucuronic acid or β‐methoxyneuraminic acid, in doses which had no effect on blood pH or on the condition of the animals.
The results confirm the antithrombotic effect of NANA previously demonstrated with another technique.
THE ROLE OF THE HYPOGASTRIC NERVE IN BLADDER AND URETHRAL ACTIVITY OF THE DOG
Authors: CREED KATE E. 
Published: July 2012

Stimulation of the hypogastric nerves increased the pressure in both the bladder and urethra of anaesthetized female dogs.
The responses were reduced but not abolished by the α‐adrenoceptor antagonist phentolamine, whereas the β‐adrenoceptor antagonist propranolol was either without effect or increased the responses. Atropine, methysergide and hexamethonium were without effect.
Close arterial injection of phenylephrine increased and isoprenaline decreased urethral pressure but both produced only a slight increase in bladder pressure.
Hypogastric nerve stimulation reduced subsequent responses of the bladder and urethra to pelvic nerve stimulation or to close arterial injection of acetylcholine. Isoprenaline, but not phenylephrine, also had an inhibitory action and 5‐hydroxytryptamine enhanced the responses.
In the presence of hexamethonium the inhibitory action of isoprenaline still occurred but 5‐hydroxytryptamine no longer enhanced the responses, suggesting that 5‐hydroxytryptamine acts on the ganglia and isoprenaline acts, at least partially, on smooth muscle.
These results suggest that the role of the hypogastric nerves may be to modify inputs to the bladder and urethra as well as to act directly on the smooth muscle.
EFFECTS OF SUBSTANCE P INJECTED INTO THE SUBSTANTIA NIGRA
Authors: JAMES THOMAS A. , STARR MICHAEL S. 
Published: July 2012

Behavioural and biochemical effects of substance P (SP, 1 to 10 μg) administered in a small volume to discrete areas of the rat's brain were studied by means of a refined microinjection technique.
SP injected unilaterally into the zona reticulata of the substantia nigra elicited dose‐dependent contraversive circling and an increase in dopamine turnover in the ipsilateral striatum. SP applied to the zona compacta or zona lateralis, or to the medial lemniscus, evoked ipsiversive turning with a fall in dopamine turnover and a rise in 5‐hydroxytryptamine (5‐HT) turnover in the corresponding striatum.
In both cases the onset of turning was immediate, reached a peak at about 5 min and lasted for 10 min. Both types of behaviour were blocked by haloperidol and exaggerated by nialamide.
Unilateral injections of SP given into the crus cerebri, zona incerta, caudate nucleus, putamen or globus pallidus did not modify the animal's behaviour.
In rats pretreated with apomorphine or amphetamine, SP induced contraversive circling which was followed by locomotion in the opposite direction.
Turning responses to a second dose of SP were diminished at 3 h and reproducible at 24 h after the first injection.
Bacitracin (50 ng) injected into the zona reticulata caused ipsiversive turning. Larger intranigral doses of bacitracin (10 μg), as with intracisternal SP (10 μg), evoked ‘barrel rotation’.
No changes in the free concentrations of aspartate, glutamate, γ‐aminobutyric acid, glycine or alanine were detected in any brain region following an intracisternal injection of 10 μg SP, although glutamine levels were elevated throughout the brain 30 to 60 min later.
EFFECTS OF CONCANAVALIN A ON 5‐HYDROXYTRYPTAMINE UPTAKE BY RABBIT BLOOD PLATELETS AND ON THEIR ULTRASTRUCTURE
Authors: NISHIO H. , SEGAWA T. , TAKAGI H. 
Published: July 2012

Effects of concanavalin A (Con A) and other lectins on 5‐hydroxytryptamine (5‐HT) uptake by rabbit blood platelets and on their ultrastructure were studied.
Uptake of [3H]‐5‐HT by platelets was decreased by application of Con A, E‐PHA (lectin from Phaseolus vulgaris) and lentil‐PHA (lectin from Lens culinaris), but not by wheat germ agglutinin (WGA). Con A induced specific changes in the ultrastructure of platelets, causing (i) a change in external appearance from a discoid to an irregularly spherical shape, (ii) re‐arrangement of the canalicular system and formation of a concentric structure. These effects of Con A on platelets were antagonized by pretreatment with α‐methyl‐D‐mannoside (a‐MM), a specific inhibitor of Con A binding to glycoprotein.
The inhibition of 5‐HT uptake by Con A was antagonized by colchicine, vinblastine and sodium nitroprusside (SNP), but not by cytochalasin B.
Theophylline, papaverine and dibutyryl cyclic adenosine 3′,5′‐monophosphate (db cyclic AMP) antagonized the effect of Con A on 5‐HT uptake, but dibutyryl cyclic guanosine 3′,5′‐monophosphate had no effect. Theophylline and db cyclic AMP did not influence the effect of Con A on the ultrastructure of platelets.
It is suggested that binding of Con A to specific receptor glycoproteins can inhibit the 5‐HT uptake system of platelets. Microtubules, contractile protein and the membrane adenylate cyclase system of platelets may also be regulatory factors in this mechanism.
SHORT AND LONG‐TERM EFFECTS OF RESERPINE ON THE CONCENTRATION OF 1‐(4‐HYDROXY‐3‐METHOXYPHENYL)‐ETHANE‐1,2‐DIOL (MOPEG‐S04) IN THE BRAIN OF THE RAT
Authors: BAREGGI S.R. , GENOVESE E. , MARKEY K. 
Published: July 2012

Reserpine (1.25 mg/kg i.p.) induced an increase (172% of controls) in the concentration of 1‐(4‐hydroxy‐3‐methoxyphenyl)‐etnane‐1,2‐diol sulphate (MOPEG‐S04) in rat brain and a decrease in the noradrenaline (NA) concentration to 50% of controls 2 h after injection. At this time the MOPEG‐S04/NA ratio was 0.28. Thereafter the MOPEG‐SO4 concentration declined and the NA concentration decreased further to 28% of control.
Higher doses of reserpine (2.5 and 5 mg/kg i.p.) did not induce a larger increase in the concentration of MOPEG‐SO4.
While a second dose of reserpine (1.25 mg/kg i.p.) given 24 h after the first did not increase the MOPEG‐SO4 concentration, amphetamine (5.0 mg/kg i.p.) administration or electrical stimulation significantly increased the concentration of MOPEG‐SO4.
NA and MOPEG‐SO4 concentrations were examined during 5 days after a single dose of reserpine (1.25 mg/kg i.p.). While the concentration of NA started to return towards normal after 24 h, that of MOPEG‐SO4 remained at approximately 70% of controls during the entire period.
The probenecid‐induced accumulation rate of MOPEG‐SO4 was significantly lower 3 and 4 days after reserpine and returned to the control value on the fifth day. At this time the concentration of NA had reached 50% of the control value.
These experiments indicate that MOPEG‐SO4 is not the major metabolite of NA during the initial phase of reserpine‐induced NA release. Reserpine acts on the storage pool while amphetamine (like electrical stimulation) acts on the functional pool. During the first phase of post‐drug recovery, there is a clear decrease in NA output which appears to be regulated by the concentration of NA in the storage pool.
THE PROTECTIVE ACTION OF INOSINE ON ISOLATED ARTERIES IN HYPOXIA
Authors: BLOOM DAVID S. , COLE ARTHUR W.G. , PALMÉER T. NORMAN 
Published: July 2012

The pressor responses to injected noradrenaline (NA) of isolated perfused femoral or renal arteries of the rabbit were studied.
Vascular smooth muscle is relatively resistant to hypoxia. A combination of hypoxia and dinitro‐phenol (DNP) respiratory uncoupling was necessary to abolish the pressor response to NA. Loss of the pressor response was assumed to result from decreased capacity of arteries to form adenosine 5′‐triphosphate (ATP). Reperfusion of the hypoxic arteries with oxygenated medium resulted in recovery of the pressor response to NA.
Inclusion of inosine (10 mm) in the hypoxic perfusion medium increased significantly the rate and extent of post‐hypoxic recovery of the pressor response to NA.
Whereas the presence of inosine in the hypoxic perfusion medium aided post‐hypoxic recovery, inosine had no direct action on the pressor dose response to NA. Therefore, the action of inosine was protective as opposed to direct.
The protective action of inosine did not involve potentiation of NA binding to NA‐adrenoceptor sites (the equilibrium coefficient, Keq for NA‐receptor interaction was unaltered by hypoxia and/or inosine).
The results are discussed in terms of a presumptive mechanism whereby inosine is believed to act by maintaining intracellular adenine nucleotide concentrations in hypoxia.
EFFECTS OF PROCAINE AND EXTRACELLULAR CALCIUM CONCENTRATION ON RESPONSE OF RAT STOMACH FUNDUS MUSCLE TO ACETYLCHOLINE AND 5‐HYDROXYTRYPTAMINE
Authors: WEINSTOCK MARTA , WEISS CARMELA 
Published: July 2012

When rat stomach fundus muscle was incubated for 30 min in Tyrode solution from which calcium chloride had been omitted, there was an almost complete abolition of the contractile response to 5‐hydroxytryptamine (5‐HT) while that to acetylcholine (ACh) was still present.
The maximum tension obtainable with ACh remained the same in external calcium concentrations ranging from 0.45 to 3.6 mm, but the pD2 value increased.
A concentration of at least 0.9 mm calcium was needed to maintain a maximum contraction with 5‐HT, and the pD2 for this agent also increased significantly with increase in calcium content of the medium.
The effects of procaine on the responses of the muscle to 5‐HT and ACh were similar to the respective changes induced by lowering the calcium concentration, and were reduced by the addition of calcium.
Concentrations of 2.2 × 10−7 to 3.6 × 10−5m procaine reduced the effects of both 5‐HT and KCl and suppressed the maximum responses.
The maximum responses to KC1 and 5‐HT were restored at higher concentrations of procaine (>3.6 × 10−4m), while the effect of ACh was reduced.
It is suggested that 5‐HT, like KC1, is almost entirely dependent on extracellular calcium for inducing muscle contraction, while ACh may utilize calcium from bound stores.
ON THE ROLE OF 5‐HYDROXYTRYPTAMINE IN DRUG‐INDUCED ANTINOCICEPTION
Authors: SUGRUE M.F. 
Published: July 2012

The effects of four specific inhibitors of 5‐hydroxytryptamine (5‐HT) uptake on morphine‐, methadone‐ or pethidine‐induced antinociception was studied in rats. Antinociception was assessed by means of hot plate (55°C) reaction times. The effect of the compounds on the uptake of [3H]‐5‐HT into rat whole brain synaptosomes was also investigated.
Pretreatment with Org 6582, citalopram, zimelidine or femoxetine at doses devoid of antinociceptive activity potentiated morphine‐ but not methadone‐ or pethidine‐induced antinociception.
A temporal correlation existed between the ability of Org 6582 to potentiate morphine‐induced antinociception and to block synaptosomal [3H]‐5‐HT uptake.
5‐HT plays a critical role in the antinociceptive effect of morphine but not of methadone or pethidine.
THE EFFECTS OF GLUCOCORTICOIDS ON THE DISTRIBUTION AND MOBILISATION OF ARACHIDONIC ACID IN FAT CELL GHOSTS
Authors: LEWIS G.P. , PIPER PRISCILLA J. , VIGO CARMEN 
Published: July 2012

The prostaglandin synthesizing enzymes were found to be present in fat cell ghosts isolated from rabbit adipose tissue.
Prostaglandin E2 (PGE2) and PGF2 were synthesized by ghosts after stimulation with adrenocor‐ticotrophic hormone (ACTH).
Indomethacin was found to inhibit this synthesis but not the synthesis of lipoxygenase products.
When fat cell ghosts were stimulated by ACTH, fatty acid release was observed from both neutral lipids and phospholipids.
The arachidonic acid (AA) pool within the ghosts was identified: approximately 90% was present in the phospholipid fraction, 8.5% in the neutral lipids and 1.5% unbound.
The glucocorticoids were found to stimulate incorporation of [14C]‐AA into neutral lipids and inhibit its incorporation into phospholipids.
When fatty acid release was stimulated with ACTH, the glucocorticoids were found to inhibit the mobilisation of [14C]‐AA from the phospholipids and enhance its release from the neutral lipids.
The glucocorticoids inhibit prostaglandin formation in fat cell ghosts.
FUNCTIONAL ANTAGONISM AS A MEANS OF DETERMINING DISSOCIATION CONSTANTS AND RELATIVE EFFICACIES OF SYMPATHOMIMETIC AMINES IN GUINEA‐PIG ISOLATED ATRIA
Authors: BROADLEY K.J. , NICHOLSON C.D. 
Published: July 2012

The positive inotropic and chronotropic responses to sympathomimetic amines were examined in guinea‐pig isolated atria.
The order of potency measured from EC50 values was isoprenaline > orciprenaline > salbutamol ≥ fenoterol > terbutaline. Terbutaline and salbutamol were partial agonists on rate and together with orciprenaline and fenoterol also on tension responses.
Functional antagonism by carbachol caused a rightwards shift of the dose‐response curve and depression of the maximum response. The rate maxima for orciprenaline, fenoterol and terbutaline were above that of isoprenaline. All the tension maxima were below isoprenaline.
Dissociation constants (KA) and relative efficacies (er) were determined by analogy with irreversible antagonism.
The relative orders of affinity (KA) were isoprenaline > orciprenaline > fenoterol > salbutamol > terbutaline. Affinities were identical on rate and tension.
The relative efficacies were all greater than isoprenaline for rate responses. On tension they were the same or less than isoprenaline.
The implications of these results are discussed, in particular the fact that a partial agonist has a greater efficacy than a full agonist.
PHARMACOLOGICAL EFFECTS OF PHOSPHATIDYLSERINE LIPOSOMES: REGULATION OF GLYCOLYSIS AND ENERGY LEVEL IN BRAIN
Authors: BIGON E. , BOARATO E. , BRUNI A. , LEON A. , TOFFANO G. 
Published: July 2012

The accumulation of glucose in the brain produced by the administration of phosphatidylserine liposomes into mice has been studied by measurement of the cerebral contents of glycolytic intermediates and high‐energy compounds.
With a normal supply of oxygen to the brain, inhibition of glycolysis is indicated mainly at the phosphofructokinase step. The ratio of glucose‐6‐phosphate to fructose‐1,6‐diphosphate increased, whereas the levels of pyruvate and especially lactate decreased.
Under conditions of cerebral ischaemia, the administration of phosphatidylserine delays glycogen mobilization and ATP use. As a consequence of decreased energy utilization, the brain adenylate energy charge remains at a high level.
It is concluded that the phosphatidylserine‐induced glucose accumulation in the brain is due to reduced energy expenditure and therefore to a decrease in carbohydrate consumption. The inhibition of glycolysis by the high level of adenylate energy charge is probably the control mechanism explaining the decreased carbohydrate utilization.
EVIDENCE FOR AN INDIRECT CHOLINERGIC REGULATION OF BLOOD FLOW IN THE HYPOTHALAMUS OF CONSCIOUS RABBITS
Authors: KLUGMAN K. , MITCHELL G. , ROSENDORFF G. 
Published: July 2012

The effects of methacholine, atropine and adrenoceptor blockade on hypothalamic blood flow (HBF) were measured in conscious rabbits.
A dose of 1 μg methacholine increased HBF while smaller and larger doses had no significant effect.
The vasodilatation induced by methacholine was blocked by atropine and by chemical sympathectomy of the hypothalamus with 6‐hydroxydopamine.
The vasodilatation was reversed by propranolol but was not affected by phenoxybenzamine.
These results suggest that the vasodilator action of muscarinic receptor agonists on hypothalamic resistance vessels depends upon the integrity of a noradrenergic system, and is mediated via β‐adrenoceptors.
RESPONSES TO dl‐IBOTENIC ACID AT LOCUST GLUTAMATERGIC NEUROMUSCULAR JUNCTIONS
Authors: CLARK R.B. , GRATION K.A.F. , USHERWOOD P.N.R. 
Published: July 2012

The responses of excitatory junctions on locust skeletal muscle fibres to iontophoretically applied l‐glutamic acid and dl‐ibotenic acid, a rigidly extended analogue of glutamate, were recorded by means of intracellular microelectrodes.
Iontophoresis of l‐glutamate to junctional sites produced transient depolarizations. Ibotenate applied iontophoretically to these sites usually evoked small hyperpolarizations which probably resulted from the activation of glutamate H‐receptors on the extrajunctional membrane surrounding the junctions. However, at a minority (∼20%) of junctions, ibotenate iontophoresis evoked transient depolarizations.
Iontophoretically applied glutamate desensitized the ibotenate receptors, and vice versa. In experiments performed at junctional sites at which ibotenate depolarizations were absent, ibotenate had no effect on the responses to glutamate.
Glutamate and ibotenate junctional currents had similar reversal potentials, measured under voltage‐clamp, suggesting that the ionic bases for these currents are identical.
It is proposed that the excitation caused by ibotenate results from the activation of receptors for extended l‐glutamate and that these receptors co‐exist on the post‐junctional membranes of locust excitatory nerve‐muscle synapses with ibotenate‐insensitive glutamate receptors activated by glutamate in partially folded conformation.
IMPROVED INSULIN RECEPTOR ASSAY: EFFECTS OF AN ANTIDIABETIC SULPHONYLUREA ON LIVER MEMBRANE INSULIN RECEPTORS FROM OBESE HYPERGLYCAEMIC MICE
Authors: GREENSTEIN B.D. 
Published: July 2012

A simple assay of liver membrane insulin receptors is described, under conditions which apparently stabilized the insulin‐receptor complex. The receptor population was measured in the presence of physiological doses of radioactive hormone under conditions which minimized negative co‐operativity effects.
Equilibrium between receptor and hormone was attained in vitro within 60 min of incubation time at 13°C with no apparent loss of binding sites after 3 h of incubation.
Liver membranes from lean mice possessed 8.8 times the receptor number per mg membrane protein measured in membranes from obese hyperglycaemic (ob/ob) littermates. After treatment of ob/ob mice with ARDF‐26 (Gliquidon; Boehringer Ingelheim Ltd) the concentration of liver membrane insulin receptors was increased 5 fold.
PHARMACOLOGY OF SCHULTZ‐DALE REACTION IN CANINE LUNG STRIP in vitro: POSSIBLE MODEL FOR ALLERGIC ASTHMA
Authors: CHAND N. , DEROTH L. , EYRE P. 
Published: July 2012

Isolated lung parenchymal strips of the dog contracted in response to histamine > carbachol > prostaglandin F2α (PGF2α) > bradykinin (Bk) > 5‐hydroxytryptamine (5‐HT). The order of the relative activity of these agents on the tracheobronchial smooth muscles (TBSM) was carbachol > 5‐HT > histamine; PGF2α and Bk were inactive. Thus there are marked differences in the responsiveness of the smooth muscle of central (trachea and bronchus) and peripheral (lung strip) airways to autonomic and autacoid agents.
Lung strips and TBSM partially contracted by carbachol, histamine or horse plasma, were relaxed by isoprenaline, PGE1 and PGE2.
Lung strips from dogs sensitized to horse‐plasma contracted in response to antigen (Schultz‐Dale anaphylactic reaction). Tachyphylaxis or desensitization to subsequent antigen challenge was invariably observed; it was followed after 1 to 2 h of rest by partial recovery of the anaphylactic response.
Mepyramine selectively antagonized responses to histamine without altering responses to carbachol and antigen.
Metiamide, an H2‐receptor antagonist, did not influence responses to histamine, carbachol or horse plasma.
Indomethacin was found to be ineffective as an inhibitor of the Schultz‐Dale anaphylactic reaction.
The results showed the presence of H1‐histamine receptors mediating constriction in the peripheral airways of the dog. Histamine and PGF2α appear to have no important role in the anaphylactic reaction in this tissue. The involvement of slow reacting substance of anaphylaxis (SRS‐A) and endoperoxides (thromboxanes) in allergic reactions of canine lung is strongly suggested.
NORADRENALINE RELEASE IN RATS DURING PROLONGED COLD‐STRESS AND REPEATED SWIM‐STRESS
Authors: BENEDICT C.R. , FILLENZ MARIANNE , STANFORD CLARE 
Published: July 2012

Plasma noradrenaline concentration in rats was measured during prolonged cold‐stress and repeated swim‐stress.
Cold exposure for 6 h caused a rise in plasma noradrenaline which reached a peak at 4 h.
Administration of desmethylimipramine and normetanephrine to block neuronal and extraneuronal uptake of noradrenaline raised plasma noradrenaline concentration without changing the pattern of the response to cold exposure.
Repeated cold exposure on subsequent days produced no change in the pattern of plasma noradrenaline concentration.
Five successive 1‐min swims at 30‐min intervals caused a rise in plasma noradrenaline concentration which was maximal after the third swim.
It is suggested that prolonged and repeated activation of sympathetic nerve terminals leads to a decline in noradrenaline release.