bluuebunny/crossref_metadata_2025_split huggingface dataset:
POSSIBLE MECHANISM OF THE DUAL ACTION OF THE NEW POLYPEPTIDE (ANTHOPLEURIN‐B) FROM SEA ANEMONE IN THE ISOLATED ILEUM AND TAENIA CAECI OF THE GUINEA‐PIG
Authors: OHIZUMI Y. , SHIBATA S. 
Published: July 2012

Anthopleurin‐B (AP‐B), a newly isolated polypeptide from a sea anemone (Anthopleura xanthogrammica) caused relaxation of the guinea‐pig isolated ileum following a transient contraction at concentrations greater than 3 × 10−9 m.
AP‐B caused a tonic contraction followed by rhythmic relaxation of the guinea‐pig isolated taenia caeci at a concentration of 3 × 10−9 m or more.
The other polypeptides, anthopleurin‐A (AP‐A) from the same species or anthopleurin‐C (AP‐C) from Anthopleura elegantissima elicited similar effects but higher concentrations were required in both tissues.
These responses induced by AP‐B in both tissues were abolished by treatment of each tissue with tetrodotoxin or incubation in a low‐Na+ medium.
In the ileum, the AP‐B‐induced contraction was markedly inhibited by atropine but not by mecamylamine, whereas the AP‐B‐induced relaxation was not affected by phentolamine or guanethidine.
The AP‐B‐induced contraction of the taenia caeci was also inhibited by atropine, but not mecamylamine. However, in contrast to the ileum, the spontaneous relaxation of this tissue was completely abolished in the presence of phentolamine or guanethidine.
These results suggest that the AP‐B‐induced contractions of both tissues are mainly caused by acetylcholine (ACh) release from the cholinergic nerve terminals and that the AP‐B‐induced relaxation of the taenia caeci is due to the excitation of adrenergic nerves, while the relaxation of the ileum is mediated through non‐adrenergic inhibitory mechanisms.
SL 75 102 AS A γ‐AMINOBUTYRIC ACID AGONIST: EXPERIMENTS ON DORSAL ROOT GANGLION NEURONES in vitro
Authors: DESARMENIEN MICHEL , FELTZ PAUL , HEADLEY P. MAX , SANTANGELO FRANCESCA 
Published: July 2012

In anticipation that centrally active γ‐aminobutyric acid (GABA)‐mimetic drugs may be clinically useful, derivatives of GABA with an imine link (Schiff base) to a lipophilic carrier have recently been prepared. The present paper concerns the actions of [α(4‐chlorophenyl)5‐fluoro, 2‐hydroxy benzilidene‐amino]‐4‐butanoate Na+, SL 75 102.
To test one aspect of the GABA‐mimetic properties of SL 75 102, this compound was compared with GABA for activity on intracellularly‐recorded neurones in rat dorsal root ganglia in vitro. On these neurones GABA, administered either by microiontophoresis or direct into the superfusion medium, causes a depolarization, due to an increased chloride conductance, followed by a period of desensitization.
The actions of SL 75 102 were in nearly all respects identical to those of GABA; parameters examined were the effects on membrane potential and input conductance, desensitization, dose‐response characteristics and sensitivity to the GABA antagonists, bicuculline and picrotoxin.
SL 75 102 was less potent than GABA (mean relative potency 0·03:1).
SL 75 102 therefore appears to be a weak agonist at GABA receptors of these neurones.
ACTIONS ON THE CARDIOVASCULAR SYSTEM OF AN INHIBITORY MATERIAL EXTRACTED FROM THE BOVINE RETRACTOR PENIS
Authors: BOWMAN ANNE , GILLESPIE J.S. , MARTIN W. 
Published: July 2012

A partially purified material has been isolated from methanol extracts of the bovine retractor penis muscle. This material exerts biological activity only after treatment with acid and subsequent neutralisation. The active principle in this extract, which appears to be no known autacoid, mimics the response to stimulation of the non‐adrenergic, non‐cholinergic nerves in the bovine isolated retractor penis muscle.
This inhibitory extract did not alter the heart rate or blood pressure of the anaesthetized rat when administered either by intravenous or intra‐arterial injection, nor did it have any obvious effect on isolated cardiac muscle.
The extract produced relaxation of spiral strips of various arteries isolated from ox, cat, rabbit or rat, in which tone was induced by noradrenaline, K+ or Ba2+.
The extract also produced dilatation of the resistance vessels of the rat isolated mesenteric circulation and the rat hindquarters perfused with Krebs solution; tone was induced in these vessels by adrenaline or noradrenaline.
Lack of vasodilator activity of the extract in the whole animal appeared to be due to rapid inactivation in the blood, probably by binding to the erythrocytes.
SOME EFFECTS OF CHEMICAL IRRITANTS ON THE MEMBRANE OF THE GIANT AMOEBA
Authors: FOSTER R.W. , WESTON A.H. , WESTON K.M. 
Published: July 2012

The effects of chemical irritants on the membrane potential and input resistance of the giant amoeba, Chaos carolinense, have been investigated. The membrane potential and input resistance were −111.5 mV and 8.6 MΩ respectively
In the resting state the cell membrane of Chaos carolinense was found to be impermeable to Na+ but permeable to K+. The distribution of K+ across the cell membrane conformed to a Donnan equilibrium with the resting membrane potential being the K+ equilibrium potential
The chemical irritants dibenzoxazepine and its 2‐chloro‐ and 3‐chloro‐analogues and o‐chlorobenzylidene malononitrile produced a fall in input resistance but no change in membrane potential. It is suggested that these effects are caused by an increase in K+ permeability
The potencies of a series of chemical irritants with respect to dibenzoxazepine were measured on the giant amoeba. These potencies did not reflect those found in mammalian preparations.
CLONIDINE ACTIVATES MEMBRANE POTASSIUM CONDUCTANCE IN MYENTERIC NEURONES
Authors: MORITA K. , NORTH R.A. 
Published: July 2012

Intracellular recordings were made from neurones in the myenteric plexus of the ileum removed from guinea‐pigs. The effects of clonidine and adrenaline on membrane potential and resistance were observed
Clonidine (100 pM‐30 nM) caused a concentration‐dependent membrane hyperpolarization associated with a fall in neurone input resistance
The amplitude of the clonidine hyperpolarization, but not the conductance increase, was greater in cells with lower resting potentials and smaller in more polarized neurones. In a given cell, membrane hyperpolarization decreased and membrane depolarization increased the clonidine effect
Low potassium solutions enhanced and high potassium solutions reduced the hyperpolarizing action of clonidine but did not significantly change the conductance increase caused by clonidine
The concentration‐effect curve for clonidine was displaced to the left when the extracellular calcium concentration was reduced. Conversely, clonidine was almost ineffective in elevated calcium concentrations. This was true for both the hyperpolarization and the conductance increase
It is suggested that clonidine activates a potassium conductance by causing an elevation in the free intracellular calcium concentration
Clonidine reversibly depressed the amplitude of the nicotinic fast excitatory postsynaptic potential and the noncholinergic slow excitatory postsynaptic potential
All the effects of clonidine were shared by adrenaline and the actions of both were reversed or prevented by phentolamine (100 nM‐1 μM).
THE EFFECTS OF PIPERAZINE ON RAT SYMPATHETIC NEURONES
Authors: CONNOR J.D. , CONSTANTI A. , DUNN P.M. , FORWARD ANNE , NISTRI A. 
Published: July 2012

The neuronal effects of the anthelmintic piperazine (Pip) on rat sympathetic ganglia were studied in vitro by means of intracellular and extracellular recording techniques
Surface potential recordings indicated that Pip (0.1–10 mM as citrate, 1–30 mM as hexahydrate) produced a sustained depolarization (reversible on washing) of rat ganglia. γ‐Aminobutyric acid (GABA, 1–100 μM) also evoked reversible depolarizations but, unlike Pip, responses to the higher doses of GABA declined during a 2 min exposure. Depolarizations produced by Pip or carbachol (but not GABA) were markedly depressed by hexamethonium bùt only slightly by bicuculline or picrotoxin
Intracellular recordings revealed that Pip‐induced depolarizations were accompanied by an increase in membrane conductance and a broadening and depression of the directly‐evoked spike
In the presence of hexamethonium (1 mM), the responses to Pip hexahydrate and to cholinoceptor agonists were abolished, but Pip citrate still changed the spike configuration and induced membrane hyperpolarization with a small conductance increase. These residual effects were mimicked by superfusing with Na citrate or Ca2+‐free medium, suggesting that significant Ca2+ binding by the citrate anion of the Pip salt was probably responsible for the observed activity of Pip citrate in the presence of hexamethonium
It is concluded that on rat ganglia Pip is a nicotinic agonist, with no detectable GABA‐mimetic activity.
PROSTAGLANDINS RELEASE PLASMA ‘RECIPROCAL COUPLING FACTOR’ IN ANAESTHETIZED RATS
Authors: HOULT J.R.S. , MOORE P.K. 
Published: July 2012

Prostaglandins E1, E2, I2 and endoperoxide analogue U46619 injected intra‐arterially (i.a.) into anaesthetized rats at 2 μg/kg caused a substantial increase within 60 min of the plasma activity of prostaglandin ‘reciprocal coupling factor’ (RCF). RCF is the provisional name for the component(s) of plasma which inhibit microsomal prostaglandin synthesis and enhance cytosolic prostaglandin breakdown
RCF is not released by inactive metabolite 13, 14‐dihydro‐15‐keto prostaglandin E2 (10 μg/kg, i.a.) or acetylcholine or histamine (2 μg/kg, i.a.)
We suggest that release by prostaglandins of RCF could provide the basis in vivo for a negative feedback mechanism controlling the activity of the prostaglandin system.
ELECTRICAL PROPERTIES OF SMOOTH MUSCLE CELL MEMBRANE AND NEUROMUSCULAR TRANSMISSION IN THE GUINEA‐PIG BASILAR ARTERY
Authors: KARASHIMA TSUYOSHI , KURIYAMA HIROSI 
Published: July 2012

The membrane properties of smooth muscle cells and neuromuscular transmission in the guinea‐pig basilar artery were investigated by use of microelectrodes
The membrane potential was −47.0 mV and the muscle tissue possessed cable‐like properties as determined by the current‐voltage relationships. The mean value of the space constant was 0.78 mm
An outward current produced a graded response and, in some cases, spike generation. This membrane response was enhanced in the presence of tetraethylammonium (TEA, 5 mM), and an increased concentration of TEA (10 mM) generated spontaneous spikes in most of the cells. Action potentials induced by TEA were abolished in the presence of MnCl2 (5 mM) but not by isoprenaline (4×10−6M)
Acetylcholine (ACh), over 10−7 M, hyperpolarized the membrane and decreased the membrane resistance. This hyperpolarization increased in the presence of low [K]o (below 5.9 mM), but decreased in [K]o concentrations over 17.8 mM. Pretreatment with atropine (10−6 m) suppressed the ACh‐induced hyperpolarization. Therefore, this action of ACh is due to an increase in the K‐conductance of the membrane produced by activation of the muscarinic receptors
Noradrenaline in concentrations up to 10−4m did not modify the membrane potential and resistance, while 10−5M, histamine, 5‐hydroxytryptamine and adenosine triphosphate (ATP) depolarized the membrane. The depolarization induced by histamine or ATP was suppressed by reducing [Na]o. The histamine‐induced depolarization was accompanied by an increase and the ATP‐induced one by a decrease in the membrane resistance. The action of histamine was suppressed by treatment with H1‐ but not H2‐receptor blocking agents (dephenhydramine and cimetidine, respectively)
Perivascular nerve stimulation (0.2 ms pulse duration) evoked excitatory junction potentials (e.j.ps). An increase in the number and frequency of stimuli enhanced the e.j.p. amplitude. In the presence of 1 mM TEA, a spike was evoked on the e.j.ps. A very high concentration of phentolamine (3.6 × 10−4 m) or the usual concentration of tetrodotoxin (10−7 m) abolished the generation of e.j.ps. Spontaneously generated miniature e.j.ps were never recorded from the resting membrane
The results are discussed in relation to regional specificities of smooth muscle cells of cerebral arteries in the guinea‐pig.
INCREASE OF ACETYLCHOLINE‐RECEPTOR SENSITIVITY BY ADENOSINE TRIPHOSPHATE: A NOVEL ACTION OF ATP ON ACh‐SENSITIVITY
Authors: AKASU T. , HIRAI K. , KOKETSU K. 
Published: July 2012

The sensitivity of the nicotinic acetylcholine (ACh)‐receptor, measured as the amplitude of ACh‐current induced by iontophoretic application of ACh to the frog skeletal muscle endplate, was increased by the action of adenosine triphosphate (ATP)
This potentiation was not due to the effect of ATP on ACh‐esterase, since the increase of the sensitivity could also be demonstrated by use of carbachol (CCh)
Kinetic analysis of the effect of ATP on the dose‐response curve of CCh‐current suggests that ATP increases the ACh‐sensitivity by acting on the allosteric site of receptor‐ionic channel complex without changing the affinity of ACh for its recognition site
The equilibrium potential and the life‐time of the endplate current (e.p.c.) are not altered by the presence of ATP
These results suggest that ATP increases the ACh‐sensitivity by increasing either the conductance of unit channels or the total number of available channels.
DEMONSTRATION OF BOTH β1‐ AND β2‐ADRENOCEPTORS MEDIATING RELAXATION OF ISOLATED RING PREPARATIONS OF RAT PULMONARY ARTERY
Authors: O'DONNELL STELLA R. , WANSTALL JANET C. 
Published: July 2012

Cumulative concentration‐response (relaxation) curves to three β‐adrenoceptor agonists, fenoterol (β2‐selective), isoprenaline (non‐selective) and noradrenaline (β1‐selective) were obtained on isolated ring preparations of rat pulmonary artery contracted with 15 mM KCl. α‐Adrenoceptors and neuronal and extraneuronal uptakes were blocked with phenoxybenzamine. The agonist concentration‐response curves were reproducible.
Responses to each of the three agonists could be blocked by the β‐adrenoceptor antagonists atenolol (β1‐selective) or ICI 118,551 (β2‐selective) confirming the presence of β‐adrenoceptors.
The relative potencies of the agonists were isoprenaline: fenoterol: noradrenaline = 100: 38: 1.4. This indicated that the predominant β‐adrenoceptor type was β2.
Schild plots were obtained for atenolol and ICI 118,551 using the three different agonists. For each antagonist the location of the Schild plot varied depending on which agonist was used. This indicated that the β‐adrenoceptor population mediating relaxation responses to β‐adrenoceptor agonists was not homogeneous.
Atenolol was most potent when noradrenaline was the agonist and ICI 118,551 was most potent when fenoterol was the agonist.
It is concluded that isolated pulmonary artery ring preparations of the rat contain a mixed population of β1‐ and β2‐adrenoceptors both mediating relaxation.
THE ACTION OF PROPRANOLOL ON FACTORS CONCERNED WITH THE DELIVERY OF OXYGEN TO THE TISSUES
Authors: LEDINGHAM JOHN M. , LEES DOUGLAS C.P. 
Published: July 2012

In a previous study in conscious rats, orally administered propranolol acutely lowered cardiac output by 30.5% and oxygen uptake by 12.2%, while oxygen extraction rose by 31.5%. The present study is concerned with the way in which the rat meets its oxygen requirements against such a fall in perfusion.
The effect of known concentrations of propranolol on haemoglobin‐oxygen affinity was studied in vitro. The effect of orally administered propranolol (given acutely and chronically) was then determined and this was related to the concentration of the drug in plasma and red cells. Further studies were made on the action of propranolol on the Bohr effect and on arterial oxygen carriage.
In vitro, high concentrations of propranolol (1 × 10−4 m) influenced haemoglobin‐oxygen affinity in a biphasic manner and this was associated with changes in haematocrit and red cell and plasma pH. No change occurred in affinity after acute or chronic oral administration of the drug due to insufficient concentration in the blood. No direct action on the Bohr effect was detected.
Arterial oxygen content rose acutely due to an increase in haemoglobin concentration.
It is concluded that increased oxygen extraction in propranolol‐treated rats is not explained by the actions of the drug on haemoglobin‐oxygen affinity.
POLYMYXIN B SULPHATE PROTECTS CATS AGAINST THE HAEMODYNAMIC AND METABOLIC EFFECTS OF E. coli ENDOTOXIN
Authors: HUGHESI BERNADETTE , MADAN B.R. , PARRATT J.R. 
Published: July 2012

The intravenous administration of E. coli endotoxin (2mg/kg) in cats anaesthetized with pentobarbitone resulted in an initial acute increase in right atrial pressure and a transient systemic hypotension. Later (from 1 h onwards) there was a progressive decrease in cardiac output, a reduced right atrial filling pressure, systemic hypotension and a profound metabolic acidosis (lactate of 30±1 mg/100ml at 5h compared with 5.1 ±0.5mg/100ml pre‐endotoxin). Only one of eight animals so treated survived 8 h.
Polymyxin B sulphate, given intravenously (1 min before endotoxin) as a bolus injection (5 mg/kg) followed by a continuous intravenous infusion (additional 5 mg/kg given over a 30 min period) prevented the endotoxin‐induced pulmonary (right atrial) hypertension but not the acute systemic hypotension.
Polymyxin B sulphate reduced the delayed haemodynamic effects of endotoxin (systemic hypotension, decrease in cardiac output); all the eight animals so treated survived 8 h compared with only 1/8 of the controls.
Polymyxin B did not prevent the initial (1–3 h) and marked metabolic acidosis following endotoxin; however, after 3h, arterial lactate levels returned towards control whereas in the endotoxin‐alone group they continued to increase until death.
The mechanism of this marked protective effect of the antibiotic and the possible clinical repercussions are discussed; the most likely explanation for the protection is in chemical combination with the lipid A moiety of the endotoxin.
TOLERANCE OF GUINEA‐PIG AIRWAY MUSCLE PREPARATIONS TO RELAXANT AGONISTS INDUCED BY CHRONIC EXPOSURE TO ISO‐PRENALINE in vivo
Authors: BRINK CHARLES 
Published: July 2012

The histamine sensitivities of complete tracheal spiral preparations from guinea‐pigs were similar to those of paired half tracheal tissues.Airway muscle preparations from animals chronically treated with isoprenaline showed a significant increase in resting tone and a significant decreased responsiveness to histamine.The paired half tracheal preparations exhibited no significant difference when either their isoprenaline or theophylline sensitivities were compared.Paired half tracheal muscle preparations from chronically treated animals (0.4 μmol, 4.0 μmol, and 40.0 μmol isoprenaline, 3 times daily for 21 days, s.c.) showed a significantly reduced sensitivity to isoprenaline when compared to appropriate controls.Theophylline concentration‐effect curves for the paired half tracheal preparations from chronically treated guinea‐pigs (4.0 μmol and 40.0 μmol isoprenaline) were significantly reduced compared with appropriate controls.Indomethacin treatment reversed the isoprenaline desensitization induced by chronic treatment (0.4 μmol isoprenaline) but was ineffective in animals that received the higher doses of isoprenalinein vivo.
EFFECT OF VERAPAMIL ON THE PULMONARY VASOCONSTRICTOR ACTION OF PROSTAGLANDIN F2α AND A SYNTHETIC PGH2 ANALOGUE
Authors: ANGERIO ALLAN D. , FITZPATRICK THOMAS M. , KOT PETER A. , RAMWELL PETER W. , ROSE JOHN C. 
Published: July 2012

The vasopressor response to prostaglandin F2α (PGF2α) and to ((15S)‐hydroxy‐11α, 9α‐(epoxymethano)‐prosta‐5Z, 13E‐dienoic acid) (U‐46619) in the canine isolated lung lobe was significantly attenuated following the administration of verapamil.
The pressor response to arachidonic acid (AA) was not affected by the presence of verapamil.
The pulmonary pressor effect of PGF2α and U‐46619 is dependent, at least in part, on Ca2+ influx into vascular smooth muscle cells.
The pulmonary pressor response to AA cannot be attributed to PGF2α or to endoperoxide intermediates but to some other product dependent on intracellular calcium stores.
RESTORATION OF VASOCONSTRICTOR RESPONSES TO NORADRENALINE BY PROSTAGLANDIN E2 AFTER α‐ADRENOCEPTOR BLOCKADE IN RAT ISOLATED MESENTERIC ARTERY
Authors: ADEAGBO A.S.O. , OKPAKO D.T. 
Published: July 2012

The effects of prostaglandin E2 (PGE2) on responses to noradrenaline (NA) after α‐adrenoceptor blockade were studied in the isolated mesenteric artery of the rat.
Phentolamine (32 nm) tolazoline (41 μm) and yohimbine (1.28 μm) blocked NA‐induced vasoconstriction competitively with dose‐ratios of 13.9 ± 1, 22.0 ± 1 and 26.6 ± 0.9 respectively.
PGE2 (28 nm) restored responses to NA during α‐adrenoceptor blockade and reduced NA dose‐ratios to 2.8 ±0.1 (phentolamine), 5.9 ±0.4 (tolazoline) and 1.7 ±0.1 (yohimbine).
At low concentrations (0.29 nm), phenoxybenzamine blockade of NA‐induced vasoconstriction was also antagonized by PGE2.
PGE2 did not reduce the pA2 of the competitive antagonists; therefore the antagonism of α‐adrenoceptor block by PGE2 was not due to a reduction in the affinity of the antagonist for the receptor.
The calcium ionophore, A23187, also antagonized competitive α‐adrenoceptor blockade but was less potent than PGE2.
Evidence is provided to suggest that although both PGE2 and A23187 can potentiate the action of NA in this preparation, the two compounds probably reverse α‐adrenoceptor blockade by different mechanisms.
Inhibition of NA‐induced vasoconstriction caused by the calcium antagonists cinnarizine, verapamil and high concentrations of phenoxybenzamine (>2 nm) were not affected by PGE2.
It is proposed that PGE2 restores responses to NA after α‐adrenoceptor blockade by increasing intracellular Ca2+ ion concentration or by activating α‐adrenoceptor‐associated Ca2+ channels.
FURTHER ANALYSIS OF INHIBITORY EFFECTS OF PROPRANOLOL AND LOCAL ANAESTHETICS ON THE CALCIUM CURRENT IN Helix NEURONES
Authors: AKAIKE N. , ITO H. , NISHI K. , OYAMA Y. 
Published: July 2012

The effects of propranolol and local anaesthetics on Ca2+ current (ICa), individually separated from other ionic currents, in Helix neurones were studied under voltage clamp, using a suction pipette technique.
Increases in external Ca2+ concentrations overcame the inhibitory action of propranolol on lea‐Double reciprocal plots for peak ICa versus external Ca2+ concentrations in the presence or absence of propranolol did not intersect at the ordinate.
Internal application of propranolol (10−4m) inhibited ICa to about 40–60% of the control in a time‐dependent manner.
Lignocaine and procaine at concentrations of 10−3–10−2m inhibited ICa without shifting the threshold in the I‐V relationships. Internal application of lignocaine (10−3–10−2 m) also inhibited ICa: the ratio of depression of the ICa was almost equivalent to that of the agent applied externally.
The results provide evidence that propranolol inhibits ICa in a noncompetitive manner with Ca2+ at the cell membrane, and suggest that the agents may occupy the receptor site in the Ca2+ ‐channel somewhere between the outer surface and inner phase of the membrane.
INCREASED HISTAMINE‐OUTPUT FROM THE ISOLATED GASTRIC MUCOSA OF THE RAT IN RESPONSE TO PENTAGASTRIN AND METHACHOLINE
Authors: MAIN I.H.M. , PEARCE J.B. 
Published: July 2012

A rat isolated gastric mucosal preparation was used to monitor histamine output and acid secretion during stimulation by different secretagogues.
In non‐stimulated preparations, spontaneous histamine output decreased over 450 min.
Stimulation of secretion with 4(5)‐methylhistamine or dibutyryl cyclic adenosine 3′,5′‐monophosphate (db cyclic AMP) and theophylline did not influence histamine output.
Pentagastrin, gastrin and methacholine increased both acid secretion and histamine output. Pentagastrin and gastrin mobilized six times more histamine in relation to acid secretion than did methacholine.
Spontaneous histamine output and secretagogue‐induced increases were unaffected by changes in external Ca2+ (0.0 to 7.2 mm) or Mg2+ (1.2 to 4.8 mm).
These results support the hypothesis that mucosal histamine plays a more important role in the action of gastrin than of cholinomimetics on the parietal cell.