bluuebunny/crossref_metadata_2025_split huggingface dataset:
INHIBITION BY SUBSTANCE P OF SOME PERIPHERAL ACTIONS OF ACETYLCHOLINE IN THE CAT
Authors: CLARK S.L. , RYALL R.W. 
Published: July 2012

The effect of substance P on contractions of the nictitating membrane and pressor responses to acetylcholine (ACh) and dimethylphenyl‐piperazinium (DMPP) which were mediated via nocotinic receptors was studied in cats anaesthetized with chloralose.
Substance P (2–20 nmol) injected into the lingual artery giving estimated concentrations in arterial blood of 10−6 to 10−5 m, or intravenously giving estimated concentrations in blood of 10−8 to 10−7 m, reduced hexamethonium‐sensitive but not atropine‐sensitive responses.
The pressor effects of ACh and DMPP injected intra‐arterially in atropinized and non‐atropinized cats respectively were consistently attenuated by substance P given intra‐arterially or intravenously.
The contractile effect of ACh in atropinized and of DMPP in non‐atropinized cats was attenuated by substance P injected intra‐arterially but only rarely when the polypeptide was injected intravenously.
The depressor effects of substance P per se were variable in magnitude and duration as were the inhibitory effects upon nicotinic receptors. The depressor and inhibitory effects of substance P were unrelated.
There was desensitization to all of these effects of substance P which probably contributed to the variation in the magnitude of the effects observed.
Substance P had no effect on muscarinic actions of acetyl‐β‐methylcholine on the nictitating membrane or blood pressure.
The results are discussed in relation to the ubiquity of the modulatory actions of substance P on nicotinic receptors and in relation to the possible physiological significance of the action.
HOMOGENEOUS AND NON‐HOMOGENEOUS DISTRIBUTION OF INHIBITORY AND EXCITATORY ADRENOCEPTORS IN THE LONGITUDINAL MUSCLE OF THE GUINEA‐PIG ILEUM
Authors: BAUER V. , KURIYAMA H. 
Published: July 2012

The effects of adrenoceptor agonists and antagonists on spontaneous and evoked membrane activities of longitudinal muscle cells from different parts of the guinea‐pig ileum were observed, using microelectrode methods.
Isoprenaline inhibited the generation of spikes in cells in the terminal (0–3 cm from the ileocaecal valve) and proximal (more than 50 cm from the ileocaecal valve) regions of the ileum, with no change on the membrane potential and ionic conductance of the membrane. These actions of isoprenaline were abolished by propranolol.
Noradrenaline and phenylephrine depolarized the membrane and increased both the spike frequency and ionic conductance of cell membranes of the terminal ileum, whereas noradrenaline and clonidine hyperpolarized the membrane, increased the ionic conductance of the membrane and inhibited the spontaneously generated spikes from cells of the proximal ileum. The excitatory effect of phenylephrine in the cells of the proximal ileum and the inhibitory effect of clonidine on cells of the terminal ileum were less pronounced.
The excitatory actions of noradrenaline or phenylephrine were antagonized by prazosin and phentolamine, but not by yohimbine, whereas the inhibitory actions of noradrenaline or clonidine were antagonized by yohimbine and phentolamine but not by prazosin.
The cholinergic e.j.ps evoked by field stimulation to the tissue were not affected by isoprenaline or phenyleprine but were inhibited by noradrenaline and clonidine, in both the terminal and proximal regions of the ileum. These actions of noradrenaline and clonidine were antagonized by yohimbine but not by prazosin.
The results indicate that in the myenteric plexus and longitudinal muscle tissues of the guinea‐pig ileum there are prejunctional inhibitory (α2), postjunctional inhibitory (α2 and β) and postjunctional excitatory (α1) adrenoceptors. The homogeneous distributions of prejunctional α2‐ and postjunctional β‐adrenoceptors in the ileum are responsible for inhibitions of cholinergic excitatory junction potentials (e.j.ps) and spontaneous spike activities, respectively. The density of distribution of the postjunctional α1‐adrenoceptors is higher in the terminal than in the proximal regions, and these distributions are reversed in the case of the postjunctional α2‐adrenoceptors. The postjunctional α1‐adrenoceptors are probably responsible for the membrane depolarization and α2‐adrenoceptors for the hyperpolarization induced by catecholamines.
TRICYCLIC ANTIDEPRESSANTS VARY IN DECREASING α‐ADRENOCEPTOR SENSITIVITY WITH CHRONIC TREATMENT: ASSESSMENT WITH CLONIDINE INHIBITION OF ACOUSTIC STARTLE
Authors: DAVIS MICHAEL , MENKES DAVID B. 
Published: July 2012

Clonidine inhibition of the acoustic startle reflex in the rat was used as a behavioural measure of α2‐adrenoceptor sensitivity following acute or chronic administration of tricyclic antidepressants.
Chronic (14 day) administration of desipramine (10 mg/kg, i.p.) attenuated the depressant effect of clonidine (20 or 40 Mg/kg) on the startle reflex.
No change in response to clonidine was obtained after chronic treatment with two other tricyclic antidepressants, amitriptyline (10 mg/kg) or iprindole (5 mg/kg).
Acute administration of these tricyclics (1 h) did not modify the effect of clonidine on startle.
It is suggested that the development of α2‐adrenoceptor subsensitivity produced by chronic tricyclics may be unique to those compounds, such as desipramine, which are active in blocking the uptake of noradrenaline.
INFLUENCE OF CHLORALOSE AND PENTOBARBITONE SODIUM ON ATRIOVENTRICULAR CONDUCTION IN DOGS
Authors: DUCHENE‐MARULLAZ P. , FABRY‐DELAIGUE R. , GUEORGUIEV G. , KANTELIP J.P. 
Published: July 2012

Atrial pacing at progressively increasing frequencies was performed on unanaesthetized dogs through electrodes placed aseptically in the wall of the right atrium and exteriorized in the neck region.
Heart rate and two atrioventricular conduction (AVC) parameters, namely the Wenckebach Point (one or two systole block at the end of expiration)‐and the maximum atrioventricular conduction frequency (the frequency of pacing for which ventricles do not follow any auricular stimulation) were measured by electrocardiography.
Chloralose (0.08 g/kg i.v.) did not affect either heart rate or AVC but significantly reduced the effect of atropine (0.1 mg/kg i.v.) on all three parameters measured. The effect of isoprenaline (0.25 μg kg−1 min−1) remained unchanged.
Pentobarbitone Na (25 mg/kg i.v.) increased heart rate and usually caused the Wenckebach Point to disappear. It reduced the effects of atropine but did not modify those of isoprenaline.
In view of these results we suggest that pentobarbitone Na be avoided as an anaesthetic agent in AVC studies. It is possible to dispense with an anaesthetic agent if the technique described here is used.
FREQUENCY‐DEPENDENT DEPRESSION OF GANGLIONIC TRANSMISSION BY PROPRANOLOL AND DILTIAZEM IN THE SUPERIOR CERVICAL GANGLION OF THE GUINEA‐PIG
Authors: ITO H. , NISHI K. 
Published: July 2012

Effects of propranolol and diltiazem on ganglionic transmission in the superior cervical ganglion of the guinea‐pig were investigated with intracellular recording techniques.
Propranolol and diltiazem (5 × 10−6‐10−5 m) induced a transmission failure in the ganglion upon preganglionic nerve stimulation at high frequency (25–30 Hz) without affecting action potentials induced by direct stimulation of the soma membrane, or potentials induced by iontophoretically applied acetylecholine.
The results suggest that propranolol and diltiazem may act on preganglionic nerve terminals to inhibit Ca2+ influx in a frequency‐dependent manner. These agents may depress excess sympathetic activity without much affecting normal ganglionic transmission.
THE EFFECTS OF THEOPHYLLINE AND 4‐(3‐BUTOXY‐4‐METHOXYBENZYL)‐2‐IMIDAZOLIDINONE (RO 20–1724) ON PROTEIN SECRETION FROM RAT PAROTID GLAND
Authors: AFARI G. , TENENHOUSE A. , VACHON C. 
Published: July 2012

The effects of two chemically distinct cyclic nucleotide phosphodiesterase (PDE) inhibitors on protein secretion from superfused rat parotid gland were studied.
In the presence of 1.0 mm Ca2+, Ro 20–1724 (10 μm), an imidazolidinone derivative, increased the secretory response to isoprenaline 100% and the isoprenaline‐dependent accumulation of adenosine cyclic 3′,5′‐monophosphate (cyclic AMP) 300–400%. At this concentration Ro 20–1724 alone did not cause protein secretion, accumulation of cyclic AMP or significantly inhibit PDE activity in cell‐free preparations from parotid gland.
In the absence of added Ca2+ and in the presence of 1.0 mm EGTA, Ro 20–1724 inhibited the secretory response to isoprenaline 65% while increasing isoprenaline‐dependent cyclic AMP accumulation 200%.
In the presence of Ca2+, theophylline (10 mm) stimulated protein secretion but did not cause the accumulation of cyclic AMP. When combined with isoprenaline the rate of secretion was greater than the sum of the effects of the individual drugs but there was no effect of theophylline on the isoprenaline‐dependent accumulation of cyclic AMP.
Theophylline‐stimulated protein secretion is increased by omitting Ca2+ from the superfusion medium without any detectable change in cyclic AMP accumulation. Under these conditions Ro 20–1724 inhibits theophylline‐stimulated protein secretion and the maximum rate of protein secretion in the presence of isoprenaline and theophylline is no greater than that seen with either agent alone.
It is concluded that the theophylline effects do not result from inhibition of PDE. It is suggested that the primary action of both drugs on parotid gland acinar cells is to alter the distribution of intracellular Ca2+. Ro 20–1724 may also inhibit Ca2+/calmodulin activated enzymes such as PDE.
α‐ADRENOCEPTOR BLOCKING PROPERTIES OF RAUBASINE IN PITHED RATS
Authors: DEMICHEL PATRICIA , GOMOND PATRICK , ROQUEBERT JACQUES 
Published: July 2012

Raubasine was compared with yohimbine and corynanthine in pithed rats. Antagonist activity at α1‐adrenoceptors was evaluated on the pressor response to electrical stimulation of the spinal sympathetic outflow and to phenylephrine administration, both being reduced by raubasine in the dose range 1 to 4 mg/kg. Corynanthine was quantitatively similar, but yohimbine was not only less potent but also in doses of 0.125 to 0.5 mg/kg enhanced the effects of electrical stimulation.
Antagonist activity at α2‐adrenoceptors was determined against the inhibitory effects of clonidine on tachycardia induced by electrical stimulation of cardiac sympathetic nerves and against the pressor responses to B‐HT‐933 injection. Raubasine up to 4 mg/kg, like corynanthine, did not affect the pressor responses to B‐HT‐933 nor did it reduce the inhibitory effect of clonidine. By contrast yohimbine reduced the response to BHT‐933 and antagonized clonidine as well as enhancing the tachycardia caused by electrical stimulation.
The results indicate that, in vivo, raubasine, like corynanthine, is a selective antagonist at α1‐adrenoceptors and that yohimbine is more potent in blocking α2‐than α1‐adrenoceptors.
EFFECT OF MUSCARINE ON RELEASE OF CATECHOLAMINES FROM THE PERFUSED ADRENAL GLAND OF THE CAT
Authors: KIRPEKAR S.M. , PRAT J.C. , SCHIAVONE M.T. 
Published: July 2012

The secretory effect of muscarine was studied in the perfused adrenal gland of the cat. During perfusion of the adrenal gland with Krebs‐bicarbonate solution containing muscarine 480 μm, the rate of catecholamine (CA) secretion was 2.02 ± 0.43 μg/2 min in the first 2 min; thereafter, CA output declined only moderately, to reach about 70% of the initial value after 10 min. Secretory responses to brief infusions of muscarine remained reproducible for at least the first 3 infusions.
When the adrenal gland was perfused with muscarine (480 μm), infusions of high K+, nicotine, or veratridine produced their usual responses. A 100 fold lower dose of muscarine also failed to modify these responses.
During perfusion with high K+, muscarine evoked a secretory response that was only slightly smaller than the response to muscarine alone.
It is concluded that muscarine and nicotine activate CA secretion in the cat adrenal gland by independent mechanisms and that the muscarinic response, unlike the nicotinic response, is not readily desensitized.
DISSIMILAR INFLUENCES OF SOME INJECTABLE ANAESTHETICS ON THE RESPONSES OF RETICULOSPINAL NEURONES TO INHIBITORY TRANSMITTERS IN THE LAMPREY
Authors: CULLEN K.D. , MARTIN R.J. 
Published: July 2012

Intracellular recordings were made from identified bulbar reticulo‐spinal neurones in the medulla of lamprey ammocoetes. Responses to iontophoretically applied inhibitory transmitters were measured as changes in membrane potential and input resistance.
Dose‐dependent alterations in the responses to γ‐aminobutyric acid (GABA) and glycine during bath application of injectable anaesthetic drugs were measured; the compounds used were pentobarbitone, ketamine, metomidate and the steroid mixture alphaxalone/alphadolone (Saffan).
GABA responses were potentiated by pentobarbitone (1–3 × 10−4m) and prolonged by ketamine (3.7 × 10−5m); but depressed by high concentrations (10−3m) of all drugs, as well as by anaesthetic concentrations of alphaxalone (1–3 × 10−5m).
Glycine responses were depressed by alphaxalone (1–3 × 10−5m) and by supra‐anaesthetic concentrations of ketamine (3.7 × 10−4 m) and metomidate (1.8 × 10−3m). No drug potentiated the glycine responses.
In the absence of an effect common to the 4 anaesthetics, it is concluded that neither potentiation nor inhibition of all GABA or glycine responses is an essential feature of anaesthesia. However, effects comparable to those described here may contribute to the overall clinical picture during anaesthesia of higher vertebrates. The findings do not support the notion that all anaesthetic agents act on biological membranes by a single mechanism.
INTERACTION OF NEUROTENSIN WITH THE SUBSTANCE P RECEPTOR MEDIATING HISTAMINE RELEASE FROM RAT MAST CELLS AND THE FLARE IN HUMAN SKIN
Authors: FOREMAN J.C. , JORDAN C.C. , PIOTROWSKI W. 
Published: July 2012

Substance P induced histamine release from rat peritoneal mast cells in a dose‐dependent manner over the concentration range 1 to 10 μm.
At concentrations in the range 2.5 to 10 μm, neurotensin produced only about 5% release of histamine, which was substantially less than the maximum effect obtained with substance P.
Neurotensin, 2.5 to 10 μm produced graded inhibition of histamine release induced by substance P. The inhibitory effect of neurotensin was not seen when histamine release was induced by an antigen‐antibody reaction or by the ionophore, A 23187. Some evidence was obtained to suggest that compound 48/80 may interact with the same receptor as substance P and neurotensin.
[d‐Arg8]neurotensin, [d‐Arg9]neurotensin, xenopsin and the C‐terminal octapeptide of substance P (SP4–11) all inhibited histamine release by substance P, but physalaemin did not.
Neurotensin inhibited the wheal and flare reactions induced by substance P in human skin.
[d‐Trp7,9]substance P released histamine from rat mast cells and was about 12 times more potent than substance P itself. [d‐Trp7,9]SP1–11 also produced wheal and flare responses in human skin, being 1.8 times more potent than substance P in the production of flare.
THE ACTIONS OF SOME ESTERS OF 4‐HYDROXYQUINUCLIDINE ON GUINEA‐PIG ILEUM, ATRIA AND RAT FUNDUS STRIP
Authors: BARLOW R.B. , KITCHEN R. 
Published: July 2012

The acetyl, phenylacetyl, and diphenylacetyl esters of 4‐hydroxyquinuclidine and their methiodides have been prepared.
4‐Diphenylacetoxyquinuclidine methiodide has higher affinity for muscarinic receptors than 4‐diphenylacetoxy‐N‐methylpiperidine methiodide (4‐DAMP methiodide) but it is less selective. At 30°C its affinity for receptors in ileum is about 5 times that for receptors in atria, a difference similar to that found with diphenylacetoxytrophine methiodide. With 4‐DAMP methiodide affinity for receptors in the ileum is over 10 times that for receptors in atria.
4‐Diphenylacetoxyquinuclidine methiodide has higher affinity for muscarinic receptors than 3‐diphenylacetoxyquinuclidine hydrochloride or its methiodide.
4‐Acetoxyquinuclidine hydrochloride has less than one‐hundredth of the activity of 3‐acetoxyquinuclidine hydrochloride (acecyclidine) on guinea‐pig ileum, atria, and rat fundus: however, 4‐acetoxyquinuclidine methiodide is consistently more active than its 3‐isomer, though it is only about 1/25 times as active as acecyclidine.
4‐Acetoxyquinuclidine hydrochloride is only a poor substrate for electric eel acetylcholinesterase: its affinity is similar to that of acecyclidine but it is greatly reduced by methylation.
The relations between the structure and activity of the agonists are very different from the relations between the structure and affinity of the antagonists, which supports the view that agonists and antagonists bind to different conformations of the muscarinic receptor.
POTASSIUM ACTIVATION OF [3H]‐CHOLINE ACCUMULATION BY ISOLATED SYMPATHETIC GANGLIA OF THE RAT
Authors: HIGGINS A.J. , NEAL M.J. 
Published: July 2012

The effect of K‐depolarization on the uptake of low and high concentrations of [3H]‐choline by isolated superior sympathetic ganglia of the rat has been studied.
In unstimulated ganglia, the uptake of [3H]‐choline (0.1 μm) (‘high affinity uptake’) was unaffected by denervation or by hemicholinium‐3 (HC‐3), suggesting uptake by structures other than cholinergic nerve terminals.
K‐depolarization of the ganglia increased [3H]‐choline accumulation by the high affinity uptake process but in contrast the ‘low affinity’ accumulation of [3H]‐choline (100 μm) was decreased.
The K‐activated, ‘high affinity’ component of choline uptake was highly sodium‐dependent, inhibited by HC‐3, and was abolished by denervation.
In incubation conditions designed to prevent transmitter release (Ca‐free medium and high‐Mg medium), the K‐activated uptake of [3H]‐choline was abolished.
It is concluded that in unstimulated ganglia, there is little choline uptake by nerve terminals. However, when the terminals are depolarized, choline uptake is increased by the activation of a sodium‐dependent, HC‐3‐sensitive transport process. The activation of this uptake process is apparently associated with the release of acetylcholine from the terminals, or by changes in ionic fluxes, and not by the depolarization per se.
SELECTIVE α1‐AND α2‐ADRENOCEPTOR AGONIST‐INDUCED CONTRACTIONS AND 45Ca FLUXES IN THE RAT ISOLATED AORTA
Authors: GODFRAIND T. , MILLER R.C. , LIMA J. SOCRATES 
Published: July 2012

Contractile responses produced by the α1‐adrenoceptor selective agonist, phenylephrine, and the α2‐adrenoceptor selective agonists, oxymetazoline and clonidine, have been compared to those produced by noradrenaline (non selective) in the rat aorta.
The relative order of potency of the agonists was noradrenaline > phenylephrine > clonidine > oxymetazoline. Noradrenaline and phenylephrine produced similar maximal responses. The maximal responses produced by oxymetazoline and clonidine were about 59% and 24% respectively of those produced by noradrenaline.
Concentrations of agonists producing maximal contractions exhibited different response‐time relationships. Responses to noradrenaline and phenylephrine were biphasic while responses induced by oxymetazoline and clonidine were monophasic.
In calcium‐free solution, contractions stimulated by oxymetazoline and clonidine were almost abolished while those stimulated by noradrenaline and phenylephrine were reduced by about 60–70%. The calcium entry blocker, cinnarizine, almost completely inhibited responses to oxymetazoline and clonidine and reduced noradrenaline‐ and phenylephrine‐stimulated responses by about 60%.
All the agonists stimulated the uptake of 45Ca into the La3+‐resistant Ca2+ fraction of the artery but only noradrenaline and phenylephrine stimulated the efflux of 45Ca into calcium‐free solution. The 45Ca uptake stimulated by oxymetazoline and clonidine was abolished by cinnarizine and that stimulated by noradrenaline and phenylephrine was reduced by about 85%.
It is concluded that clonidine and oxymetazoline stimulate contractions that are totally dependent on extracellular calcium. Noradrenaline and phenylephrine stimulate contractions that are partly dependent on extracellular calcium and partly dependent on intracellular calcium stores.
THE CONTRACTILE EFFECTS OF 5‐HYDROXYTRYPTAMINE ON THE RAT ISOLATED VAS DEFERENS
Authors: HAY D.W.P. , WADSWORTH R.M. 
Published: July 2012

5‐Hydroxytryptamine (5‐HT) (5.16–1291 μm) produced a phasic contraction followed later by rhythmic contractions in the rat vas deferens, primarily in the epididymal half. 5‐HT (129 μm) produced no response in Ca2+‐free solution. Nifedipine (0.29 μm) or verapamil (2.04 μm) inhibited the initial phasic response to 5‐HT, but inhibition of the rhythmic contractions required concentrations 5 fold (nifedipine) or 30 fold (verapamil) higher.
Methysergide (2.13 μm) abolished the phasic and reduced the frequency of the rhythmic contractions. Phentolamine (2.65 μm) did not affect the phasic response but reduced the amplitude of the rhythmic contractions. The combination of phentolamine (2.65 μm) and methysergide (2.13 μm) completely abolished the response to 5‐HT (129 μm).
Desipramine (1.32 μm) had no effect on the phasic response to 5‐HT (129 μm), but the rhythmic contractions were reduced in amplitude with no effect on their frequency.
In vasa deferentia removed from reserpine‐treated or from guanethidine‐denervated rats, both phasic and rhythmic components of the 5‐HT (129 μm) contraction were augmented due to supersensitivity.
It is concluded that the phasic component of the 5‐HT contraction is mediated by post‐junctional 5‐HT receptors, while the rhythmic component is mediated by the combination of post‐junctional 5‐HT receptors and noradrenaline released from neuronal stores. Assuming that nifedipine and verapamil are acting solely by inhibition of calcium channels, the phasic and rhythmic components of the 5‐HT response may be mediated through separate Ca2+ channels. If this is correct, one channel might be a voltage‐dependent channel and the other could be similar to, but distinct from the channel mediating the response to methoxamine.
COMPARISON OF THE ACTIONS OF CENTRALLY AND PERIPHERALLY ADMINISTERED CLONIDINE AND GUANFACINE IN THE RABBIT: INVESTIGATION OF THE DIFFERENCES
Authors: BARBER N.D. , REID J.L. 
Published: July 2012

Guanfacine was administered intravenously to rabbits and produced a dose‐dependent lowering of blood pressure.
Clonidine and guanfacine, administered to rabbits intravenously (30 μg/kg and 300 μg/kg respectively) and intracisternally (3 μg/kg and 12 μg/kg respectively) caused a similar degree of hypotension, apparently of central origin.
Saliva flow in vivo was estimated. Clonidine (30 μg/kg, i.v.) caused a significant decrease in salivation (P<0.05) for the first 50 min after injection. Guanfacine caused a significant fall (P<0.05) only at 50 and 180 min after injection.
Apparent partition coefficients for an octanol/buffer system at pH 7.4 for clonidine and guanfacine were 5.4 and 21.2 respectively.
Measurement of guanfacine levels concurrently in both plasma and brain showed that guanfacine had higher brain than plasma levels and that the brain levels were fairly constant over the 3 h measured. Brain:plasma ratios were 2.1:1, 5.3:1 and 13.6:1 after 15, 90 and 180 min respectively.
These results suggest that the long duration of action of guanfacine is due to its persistence at its central site of action.