bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE RESPONSE OF THE RABBIT RECTOCOCCYGEUS MUSCLE TO STIMULATION OF EXTRINSIC rNHIBITORY NERVES AND TO SYMPATHOMIMETIC DRUGS
Authors: KING B.F. , MUIR T.C. 
Published: July 2012

The effects of stimulating sympathetic or non‐adrenergic non‐cholinergic (NANC) nerves or of the addition of noradrenaline (NA) or isoprenaline (Iso) were investigated on carbachol‐induced tone and on contractions produced by acetylcholine (ACh) and by pelvic nerve stimulation, in the rabbit rectococcygeus muscle.
Each procedure reduced carbachol‐induced tone; sympathetic and NANC nerve stimulation were equipotent but both were less effective than sympathomimetic drugs, of which Iso was the better. Both Iso and NA, but not sympathetic nerve stimulation, inhibited the contractions produced by pelvic nerve stimulation in a concentration‐dependent manner. Against ACh‐induced contractions, only Iso was effective. The effects of NANC nerve stimulation on the motor responses to pelvic nerve stimulation or to ACh were not investigated.
The inhibitory effects of sympathetic nerve stimulation, of Iso and of NA were reduced by propranolol (3 × 10−6m) but unaffected by phentolamine (3 × 10−5m).
In the presence of high (45 mm) concentrations of KCI, Iso and NA produced a concentration‐dependent inhibition of tone that was antagonized by propranolol (3 × 10−6m).
Methoxamine (4 × 10−7 to 4 × 10−5m) and phenylephrine (5 × 10−7 to 5 × 10−5m) which interact mainly with α1 ‐adrenoceptors, produced only small, transient reductions in carbachol‐induced tone which were subject to tachyphylaxis, unlike those produced by Iso and NA. These inhibitory effects were antagonized by phentolamine (3 × 10−6m) or azapetine (3 × 10−6m).
Phenylephrine (5 × 10−4 m) and high doses (3 × 10−5m or greater) of NA enhanced the contractile response to pelvic nerve stimulation and, on occasion, produced muscle contraction. These effects were antagonized by phentolamine (3 × 10−6m).
These results suggest that inhibition of the rectococcygeus, a muscle which has no intramural nerve plexus, can be inhibited by stimulation of extrinsic NANC nerves, the transmitter for which is unknown and by sympathetic nerve stimulation via a‐ and β‐adrenoceptors located postsynaptically on the muscle. Excitatory α‐adrenoceptors may also be present.
EFFECTS OF A POTENT AND SPECIFIC β2‐ADRENOCEPTOR ANTAGONIST ON INTRAOCULAR PRESSURE
Authors: NATHANSON JAMES A. 
Published: July 2012

Physiological studies support the possibility of adrenergic regulation of aqueous humor secretion from the ciliary process, a tissue which has recently been shown to contain a predominance of β2‐adrenoceptors.
The present experiments examine the effects of a potent and highly specific β2‐antagonist (IPS 339) on intraocular pressure in the normal rabbit eye.
The observed decrease in pressure caused by IPS 339 suggests that highly specific β2‐antagonists may be useful in decreasing elevated intraocular pressure.
UPTAKE OF 5‐HYDROXYTRYPTAMINE IN THE CATECHOLAMINE CONTAINING AREAS OF THE HYPOTHALAMUS OF THE RAT AFTER TREATMENT WITH PHENELZINE AND TRYPTOPHAN
Authors: ARBUTHNOTT G.W. , ECCLESTON D. , LASZLO I. , NICOLAOU N. 
Published: July 2012

Uptake of 5‐hydroxytryptamine in the catecholamine containing nerve endings of the hypothalamus in the rat brain was found after intraperitoneal injection of phenelzine sulphate (25 mg/kg) and tryptophan (100 and 400 mg/kg).
The results were obtained by fluorescence microscopy and microspectrofluorimetry.
COMPARISON OF THE EFFECTS OF ETHYLENEDIAMINE ANALOGUES AND γ‐AMINOBUTYRIC ACID ON CORTICAL AND PALLIDAL NEURONES
Authors: PERKINS M.N. , STONE T.W. 
Published: July 2012

The actions of ethylenediamine (EDA) and structurally related compounds were investigated by microiontophoresis in Wistar rats.
EDA inhibited, via a bicuculline‐sensitive mechanism, the spontaneous firing rate of all cortical and pallidal cells tested.
The results with the analogues suggest that two amine groups are required for this neuronal depressant action whereas a carboxyl grouping is not. N‐substitution reduces the depressant effect. The length of the molecule is also critical, more than 3 methylene components seriously reducing its effectiveness. A rigid analogue of EDA, piperazine, was also active. In addition the apparent transport numbers of EDA and γ‐aminobutyric acid (GABA) were calculated, showing a close similarity between the two.
The results are discussed with respect to the possibility that EDA may represent a new class of GABA‐mimetics, or may indicate the existence of a novel diamine receptor mediating bicuculline‐sensitive inhibition in the rat CNS.
THE ASSOCIATION BETWEEN THE MELANOCYTE‐STIMULATING HORMONE RECEPTOR AND THE α2‐ADRENOCEPTOR ON THE Anolis MELANOPHORE
Authors: CARTER R.J. , SHUSTER S. 
Published: July 2012

The primary effect of catecholamines was to lighten Anolis skin previously darkened by α‐melanocyte‐stimulating hormone (α‐MSH). In concentrations above 10−7 m noradrenaline, 10−6 m adrenaline and 10−5 m dopamine, darkening of subpopulations of melanophores occurred. Subsequent experiments were concerned with the effect of low catecholamine concentrations on α‐MSH action.
The relationship between MSH receptors and α‐adrenoceptors on the Anolis melanophore was studied by a kinetic approach using the rate bioassay method and by use of α‐adrenoceptor agonists and antagonists.
α‐MSH dose‐response curves were shifted, in parallel, to the right in the presence of the catecholamines, noradrenaline, adrenaline and dopamine, and Lineweaver‐Burke plots and Arunlakshana‐Schild plots indicated that the catecholamines antagonized MSH action by a competitive mechanism.
Phentolamine had an inhibitory effect on the action of adrenaline but not on the action of MSH. Therefore MSH and catecholamine actions were mediated by separate receptors.
The classical kinetics of competition are not confined to competition at a single receptor.
The α‐adrenoceptor was defined as the α2‐subtype since (a) the α2‐selective agonist, clonidine, was found to mimic catecholamine action. (b) The α2‐selective antagonist, yohimbine, blocked the actions of clonidine and adrenaline. (c) The α1‐selective antagonist, prazosin, had negligible blocking effects on adrenaline and clonidine.
We conclude that a close association exists between the separate MSH receptor and α2‐adrenoceptor on the Anolis melanophore. The competition that takes place between MSH and catecholamines must occur after hormone‐receptor interaction, possibly through a common adenylate cyclase moiety oppositely controlled by the two receptors involved.
CHANGES IN BODY TEMPERATURE AND OXYGEN CONSUMPTION RATE OF CONSCIOUS MICE PRODUCED BY INTRAHYPOTHALAMIC AND INTRACEREBROVENTRICULAR INJECTIONS OF Δ9‐TETRAHYDROCANNABINOL
Authors: FITTON A.G. , PERTWEE R.G. 
Published: July 2012

Δ9‐Tetrahydrocannabinol (Δ9‐THC) was injected into the preoptic area of the anterior hypothalamus or into the third or fourth cerebral ventricle of the conscious mouse through a chronically implanted cannula and the effects on body temperature and oxygen consumption rate were measured.
At an ambient temperature of 22°C, injections of Δ9‐THC into the fourth ventricle (5 and 10 μg) produced dose‐dependent falls in rectal temperature. Hypothermia was also observed after injections of the drug into the hypothalamus (5 and 10 μg) or into the third ventricle (10 μg).
The hypothermia produced by Δ9‐THC was associated with a fall in oxygen consumption rate. Falls in rectal temperature and in oxygen consumption rate were significantly greater after injection of Δ9‐THC than after injection of the drug vehicle, Tween 80.
The falls in rectal temperature and oxygen consumption rate produced by injection of Δ9‐THC into the fourth ventricle were abolished by elevation of the ambient temperature from 22 to 32°C.
A pretreatment that consisted of subcutaneous injections of Δ9‐THC (20 mg/kg) given once daily for three days produced tolerance to the hypothermic effect of the drug when injected on day 4 either into the fourth ventricle (10 μg) or into a lateral tail vein (2.0 mg/kg).
The results suggest that Δ9‐THC acts centrally to alter thermoregulation in mice not only when it is injected directly into the hypothalamus or cerebral ventricles but also when it is given intravenously. After intraventricular or intravenous administration the drug may act at extrahypothalamic as well as at hypothalamic sites. The data also support the hypothesis that in mice, tolerance to the hypothermic effect of Δ9‐THC is pharmacodynamic and does not depend on changes in metabolism or distribution of the drug.
MYOTOXIC ACTIVITY OF THE CRUDE VENOM AND THE PRINCIPAL NEUROTOXIN, TAIPOXIN, OF THE AUSTRALIAN TAIPAN, Oxyuranus scutellatus
Authors: HARRIS J.B. , MALTIN C.A. 
Published: July 2012

The crude venom of the Australian taipan, Oxyuranus scutellatus and its principal neurotoxin, taipoxin, were injected into the anterolateral aspect of one hind limb of the rat.
The effects of the venom and toxin on the morphology and physiology on the underlying soleus muscles were examined.
Both the crude venom and the toxin caused necrosis and degeneration of the muscle. Damage to the peripheral muscle fibres could be seen at the light microscopic level as early as 3 h after injection of the toxic compounds.
The necrotic response was accompanied by an infiltration of phagocytic cells and an extensive oedema. The wet weight of the damaged muscles was almost doubled by 6 h.
In individual muscle fibres, necrosis was associated with the disruption of the plasma membrane and the disorganization of the myofibrils. The basal lamina of the muscle fibres was left intact.
Denervated mammalian muscles and innervated avian muscles were also destroyed by taipoxin, but immature avian muscle growing in tissue culture was resistant.
Of the 3 subunits of taipoxin, only the basic α‐taipoxin was itself myotoxic. However, its potency was enhanced by the presence of the acid γ‐subunit. The role of the neutral β‐subunit is unclear.
The period of necrosis and degeneration lasted for approximately 48 h, after which the muscle fibres began to regenerate. Regeneration took place within the surviving basal lamina, with the formation of myotubes by three days, and small, immature muscle fibres by five days. Regeneration was virtually complete by 21 days.
MEMBRANE PROPERTIES AND EXCITATORY NEUROMUSCULAR TRANSMISSION IN THE SMOOTH MUSCLE OF DOG CEREBRAL ARTERIES
Authors: FUJIWARA SHIGERU , ITOH TAKEO , SUZUKI HIKARU 
Published: July 2012

Drug actions on electrical and mechanical properties of smooth muscle cells and neuromuscular transmission in the canine cerebral arteries were investigated by use of microelectrode and isometric tension recording methods.
In the basilar and middle cerebral arteries, the resting membrane potentials were — 49.4 mV and — 51.7 mV, respectively, the length constants 0.57 mm and 0.45 mm, respectively and the time constants 142 ms and 118 ms, respectively.
Outward current pulses did not evoke the spike in either artery but did evoke the spike under conditions of pretreatment with 10 mm tetraethylammonium (TEA).
The maximum slope of depolarization produced by a ten fold increase in [K]o plotted on a log scale was 40.1 mV in the basilar artery and 42.2 mV in the middle cerebral artery. 2‐Nicotinamidoethyl nitrate, the K‐permeability accelerator, had no effect on the membrane potential.
K‐free or ouabain [10−5m] treatment slightly depolarized the membrane. Re‐addition of K [5.9 mm] hyperpolarized the membrane by several mV. Thus, the contribution of an active Na‐K pump in the membrane potential seems to be small.
In both arteries, acetylcholine, adenosine, noradrenaline and isoprenaline in concentrations up to 10−5 m did not modify the membrane potential and resistance, while 5‐hydroxytryptamine (over 10−8 m) and ATP (over 10−5 m) depolarized the membrane, decreased the membrane resistance and produced a dose‐dependent contraction. Adenosine suppressed the contraction evoked by excess [K]o(39.8 mm).
Perivascular nerve stimulation produced excitatory junction potentials (e.j.ps). Often e.j.ps were followed by a hyperpolarization. Repetitive stimulation produced facilitation after several stimuli and depression followed. In some cells, this depression appeared without facilitation.
The e.j.ps ceased with pretreatment with guanethidine (10−6 m) or tetrodotoxin (3 × 10−7 m), while phentolamine (10−7m) and yohimbine (10−7m) enhanced the amplitude of e.j.ps. ATP (10−5 m) and noradrenaline (10−6 m) supressed and prazosin had little effect on the e.j.ps. Atropine (10−6 m) also had no effect on the e.j.ps.
Specific features of the cerebral artery and systemic vascular beds were compared, and the features of adrenoceptors on the smooth muscle membrane were compared with findings in other vascular beds.
THE EFFECTS OF PARAOXON ON BLOOD PRESSURE IN THE ANAESTHETIZED AND IN THE CONSCIOUS RAT
Authors: DE NEEF J.H. , JORDAAN K.M. , PORSIUS A.J. 
Published: July 2012

Intravenous administration of paraoxon (150–825 μg/kg) to anaesthetized rats induced long‐lasting, dose‐dependent pressor effects. Only after injection of 825 μg/kg paraoxon was the pressor response followed by a depressor effect and a bradycardia that could be blocked by N‐methylatropine. Intracerebroventricular injection of paraoxon into anaesthetized rats also induced pressor effects.
In order to elucidate the mechanism of the pressor action rats were given dexetimide, N‐methylatropine, mecamylamine, phentolamine, prazosin, yohimbine, atenolol and metoprolol. If treatment with these drugs resulted in a low initial blood pressure, vasopressin was infused to elevate blood pressure to normal levels. The influence of adrenalectomy, pretreatment with reserpine and midcollicular transection was also examined.
The pressor effect of paraoxon was not influenced by N‐methylatropine or mecamylamine. However, a combination of these drugs as well as dexetimide, phentolamine or prazosin combined with yohimbine, reduced or prevented the pressor effect.
In conscious rats the effects of paraoxon and the action of antimuscarinic drugs upon the pressor response were similar to those observed in anaesthetized animals.
Acetylcholinesterase activities were measured in various brain regions and in whole blood. Paraoxon concentrations within the CNS were also measured.
It is concluded that the pressor effect of paraoxon in anaesthetized and conscious rats is mediated by a central mechanism, although a contribution of peripheral acetylcholinesterase inhibition in sympathetic ganglia to this pressor effect cannot be ruled out.
THE PRESSOR EFFECTS OF PARAOXON IN THE PITHED RAT
Authors: DE NEEF J.H. , PORSIUS A.J. 
Published: July 2012

In pithed rats paraoxon 825 μg/kg induced a short‐lasting pressor effect. Lower doses of the drug were ineffective.The pressor effect was prevented by N‐methylatropine, dexetimide and α‐receptor blocking agents but not by mecamylamine.When blood pressure of pithed rats was elevated either by the continuous infusion of vasopressin or by electrical stimulation of the pithing rod, both 275 and 825 μg/kg paraoxon induced further pressor effects. The effectiveness of various receptor blocking agents was similar to that observed in pithed rats without vasopressin.It is concluded that the pressor effect of paraoxon is mediated by ganglionic muscarinic receptors. Stimulation of these receptors by accumulated acetylcholine results in an increase in postganglionic sympathetic activity and causes pressor effects.The peripheral action of paraoxon is compared with its action in intact anaesthetized animals.
MODULATION OF BRONCHOCONSTRICTOR RESPONSES TO HISTAMINE IN PITHED GUINEA‐PIGS BY SYMPATHETIC NERVE STIMULATION
Authors: AINSWORTH GILLIAN A. , GARLAND L.G. , PAYNE A.N. 
Published: July 2012

Electrical stimulation (40V, 0.5–8 Hz, pulse width 0.5 ms) of the thoracic spinal outflow for between 10 and 120 s inhibited histamine‐induced bronchoconstriction in pithed guinea‐pigs.
The degree of this bronchodilatation varied with the position of the stimulating electrode within the spinal canal. Two maxima were identified. The first, at the level of the 9th and 10th thoracic vertebrae, was abolished by adrenalectomy. The second, at the level of the 3rd and 4th thoracic vertebrae, was associated with tachycardia and was unchanged by adrenalectomy.
The magnitude of this second bronchodilator effect varied with the frequency of stimulation. It was abolished by pretreatment with reserpine (5 mg/kg i.p. 48 and 24 h beforehand) and was competitively blocked by propranolol (0.01–1.0 mg/kg).
These observations are consistent with the view that bronchodilator tone is derived from neuronally‐released noradrenaline within the lung. The noradrenaline probably overflows from well‐innervated vasculature adjacent to sparsely innervated airways.
THE EFFECTS OF MONOVALENT AND DIVALENT CATIONS ON THE α‐ADRENOCEPTOR OF INTACT HUMAN PLATELETS
Authors: ELLIOTT J.M. , GRAHAME‐SMITH D.G. 
Published: July 2012

We have examined the effects of smonovalent and divalent cations and purine nucleotides on the binding of agonists and antagonists to the α‐adrenoceptor of intact human platelets.
Replacement of Na+ (150 mm) by NH4+ (150 mm) in the incubation medium significantly reduced the binding affinity of [3H]‐dihydroergocryptine (P<0.05) but did not alter the binding capacity. The competitive binding affinity of adrenaline and noradrenaline was unaltered.
The addition of Ca2+ (1 mm) or Mg2+ (1 mm) to the platelet suspension significantly reduced the platelet α‐adrenoceptor capacity as indicated by either [3H]‐dihydroergocryptine (P<0.05) or [3H]‐yohimbine (P<0.01; Ca2+ only).
The addition of Ca2+ (1 mm) or Mg2+ (1 mm) had no effect on the binding affinity of [3H]‐dihydroergocryptine but significantly reduced that of [3H]‐yohimbine (P<0.05). The competitive affinity of adrenaline and noradrenaline determined by inhibition of [3H]‐dihydroergocryptine binding, was unchanged in the presence of either cation.
Addition of the purine nucleotides ADP, ATP, GDP or GTP (final concentration 10 μm), either alone or in the presence of 1 mm Ca2+ or 1 mm Mg2+, had no effect on the binding of [3H]‐dihydroergocryptine or on the competitive affinity of adrenaline or noradrenaline.
We conclude that the α‐adrenoceptor of intact human platelet displays the binding characteristics of the α2L form of the receptor previously identified in the platelet lysate preparation.
THE USE OF LOW CONCENTRATIONS OF DIVALENT CATIONS TO DEMONSTRATE A ROLE FOR N‐METHYL‐D‐ASPARTATE RECEPTORS IN SYNAPTIC TRANSMISSION IN AMPHIBIAN SPINAL CORD
Authors: SMITH PETER A. 
Published: July 2012

Synaptic potentials and the responses of frog spinal cord to various acidic amino acids were examined by means of the sucrose gap recording technique.
Divalent cations (50–250 μm) specifically antagonized responses evoked at N‐methyl‐d‐aspartate (NMDA) receptors by N‐methyl d,l aspartic acid (NMDLA). The rank order of potency was Ni2+ > Co≫2+ > Mg2+ > Mn2+. Responses to glutamate and aspartate were relatively insensitive to these concentrations of divalent cations.
The rank order of potency for divalent ions (1 mm) for antagonism of synaptic transmission in bullfrog sympathetic ganglia was Mn2+ ≫ Co2+ > Ni2+ ≫ Mg2+. Thus synaptic transmission in ganglia was especially sensitive to Mn2+ whereas NMDLA responses were especially sensitive to Co2+ and Mg2+.
It was possible to depress selectively the dorsal root‐dorsal root potential (DR‐DRP) and dorsal root‐ventral root potential (DR‐VRP) of frog spinal cord using low doses of Co2+ or Mg2+ which did not affect VR‐DRP (ventral root‐dorsal root potential). It was not possible to produce this selective depression of DR‐DRP and DR‐VRP with Mn2+, as this cation non‐selectively depressed all responses.
These results suggest that: (i) divalent cations do not antagonize NMDLA responses by blocking Ca2+ channels which may mediate the response; (ii) postsynaptic NMD A receptors are activated by a neurotransmitter involved in the DR‐DRP and DR‐VRP pathways but not by any neurotransmitters involved in the VR‐DRP pathway; (iii) the neurotransmitter activating NMDA receptors in amphibian spinal cord may be an aspartate‐like substance rather than aspartate itself or glutamate.
HISTAMINE H2‐ANTAGONISTS MODIFY GASTRIC EMPTYING IN THE RAT
Authors: BERTACCINI G. , SCARPIGNATO C. 
Published: July 2012

Histamine H2‐receptor antagonists were tested for their effect on gastric emptying in the rat.
At low doses all the compounds were inactive except for burimamide which delayed and ranitidine which accelerated gastric emptying.
At high doses burimamide, metiamide, Cimetidine and oxmetidine delayed, whereas ranitidine accelerated gastric emptying; tiotidine remained ineffective.
Changes in emptying rate were not accompanied by changes in emptying pattern which, with all the compounds examined, proceeded, as in the controls, by apparent first order kinetics.
The mechanism of the ranitidine‐induced acceleration of gastric emptying seemed to be connected with an interference with the cholinergic system, whereas the mechanism of cimetidine‐ and oxmetidine‐induced slowing of gastric emptying was apparently related to cholinolytic and possibly also relaxant effects of the compounds.
These different effects of the various H2‐blockers are consistent with the idea that changes in emptying rate are independent of H2‐receptor blockade.
SPECTRUM OF THE μ‐, δ‐ AND κ‐BINDING SITES IN HOMOGENATES OF RAT BRAIN
Authors: GILLAN M.G.C. , KOSTERLITZ H.W. 
Published: July 2012

In homogenates of rat brain, the binding characteristics of tritiated opiates and opioid peptides were examined and the relative capacities of μ‐, δ‐ and κ‐binding sites of the opiate receptor determined by saturation analysis.
In competition experiments, binding of the selective μ‐ligand [3H]‐[d‐Ala2,MePhe4,Gly‐ol5]enkephalin at the μ‐site was displaced by [d‐Ala2,d‐Leu5]enkephalin with rather low affinity (KI = 12.6 nm) and more readily by the ketazocine‐like compounds (−)‐ethylketazocine (KI = 3.1 nm) and (−)‐bremazocine (KI = 0.32 nm), which also displaced the binding of [3H]‐[d‐Ala2,d‐Leu5]enkephalin from the δ‐site. In contrast, the binding to the κ‐site was easily displaced by ethylketazocine (1.0 nm) and bremazocine (0.37 nm) but not by the μ‐ligand [d‐Ala2,MePhe4,Gly‐ol5]enkephalin (KI = 2000–3000 nm) or the δ‐ligand [d‐Ala2,d‐Leu5]enkephalin (KI > 20,000 nm).
The dissociation equilibrium constant (KD) and the binding capacity (pmol/g) of the μ‐binding site were determined with the selective μ‐ligand [3H]‐[d‐Ala2,MePhe4,Gly‐ol5]enkephalin. For the δ‐site, [3H]‐[d‐Ala2,d‐Leu5]enkephalin was used in the presence of unlabelled [d‐Ala2,MePhe4,Gly‐ol5]enkephalin in order to suppress cross‐reactivity to the μ‐binding site. For the estimation of κ‐binding, [3H]‐(±)‐ethylketazocine or [3H]‐(−)‐bremazocine were used in the presence of unlabelled μ‐ and δ‐ligands for the suppression of cross‐reactivities to the μ‐ and δ‐binding sites.
In rat brain the capacity of the μ‐binding site was 7.3 pmol/g brain, that of the δ‐binding site 6.7 pmol/g brain and that of the κ‐binding site 2.0 pmol/g brain. Thus, the κ‐binding site had the lowest value whereas in the guinea‐pig brain the capacity of the μ‐binding site was lower than that of the δ‐ or κ‐binding site.