bluuebunny/crossref_metadata_2025_split huggingface dataset:
MODEL OF OPIATE DEPENDENCE IN THE GUINEA‐PIG ISOLATED ILEUM
Authors: COLLIER HARRY O.J. , CUTHBERT NIGEL J. , FRANCIS DAVID L. 
Published: July 2012

Segments of ileum, incubated for 2–24 h at 22°C with normorphine (0.01‐1.0 μm), in the presence of hexamethonium, contracted when challenged with naloxone (0.03 μm). No response to this dose of naloxone was induced either by incubation in control solution without opiate for 2–24 h or by exposure of the preparation to opiate for 30 min at 37°C.
When segments were incubated for 24 h, the size of the response to naloxone was directly related both to the normorphine concentration in the incubation fluid (0.01 to 0.1 μm), and to the concentration of naloxone applied (0.03 to 0.1 μm).
A spontaneous withdrawal contracture was elicited in ilea that had been incubated with normorphine (1.0 μm), when the normorphine‐containing bathing fluid was exchanged for one without opiate.
Normorphine restored to resting level the tension of the withdrawal contracture, whether it had been elicited spontaneously or by naloxone challenge.
Addition of naloxone (1.0 μm) to normorphine (1.0 μm) in the incubation fluid abolished the withdrawal contracture to subsequent challenge with naloxone.
Naloxone elicited a contracture from segments incubated for 24 h at 22°C with levorphanol (0.1 μm) but not from those incubated with dextrorphan.
Application of (+)‐naloxone (0.03 μm) to segments previously incubated with normorphine (0.1 μm) did not elicit a contracture.
The contracture elicited by naloxone in preparations incubated with morphine (10 μm) was associated with a reduction in sensitivity to the acute inhibitory effect of morphine on the electrically‐evoked response.
Addition of hyoscine (0.5 μm) immediately after challenge with naloxone restored the tension of the withdrawal contracture to resting level.
Tetrodotoxin (3.0 μm) given before challenge, prevented naloxone from eliciting a withdrawal contracture.
The inclusion of 5‐hydroxytryptamine (10 μm) with morphine (10 μm) inhibited the induction of tolerance to morphine.
These experiments, together with those described earlier, indicate that incubation with opiate induces a dependence in the final cholinergic motor neurones of the myenteric plexus, manifested as a contracture of the longitudinal muscle on removal of opiate or administration of an antagonist. This dependence is associated with tolerance, expressed as a decrease in sensitivity to inhibition by morphine of the electrically‐evoked contracture. Tolerance and dependence are induced and withdrawal precipitated through specific and stereospecific opiate receptors.
CHARACTERIZATION OF THE k‐SUBTYPE OF THE OPIATE RECEPTOR IN THE GUINEA‐PIG BRAIN
Authors: KOSTERLITZ H.W. , PATERSON S.J. , ROBSON L.E. 
Published: July 2012

In homogenates of guinea‐pig brain, the characteristics of the binding of [3H]‐ethylketazocine, an agonist for the putative k‐receptor, were determined by estimation of the affinity and capacity of binding, by competitive inhibition for the binding site by unlabelled ligands and by selective protection of the binding site from alkylation by phenoxybenzamine.
At 25°C the maximum number of binding sites for [3H]‐ethylketazocine was about 14pmol/g fresh brain, of which about 50% were high affinity sites.
In competition experiments, the high affinity binding of [3H]‐ethylketazocine to the k‐binding site was readily displaced by several k‐agonists but not by the selective μ‐ligand, D‐Ala2, MePhe4, Glyol5‐enkephalin or the selective δ‐ligand, D‐Ala2, D‐Leu5‐enkephalin. In contrast, the k‐agonists tested so far exhibit a high degree of cross‐reactivity with the μ‐binding site but somewhat less with the δ‐binding site. Similar specificities were observed in protection experiments.
The approximate proportions of the three subtypes of opiate receptor in the guinea‐pig brain are 25% μ‐binding sites, 45% δ‐binding sites and 30% k‐binding sites.
The endogenous opioids, Met‐enkephalin, Leu‐enkephalin and porcine β‐endorphin have only a low affinity for the k‐binding site.
DEVELOPMENT OF A SEVERE MODEL OF EARLY CORONARY ARTERY LIGATION‐INDUCED DYSRHYTHMIAS IN THE ANAESTHETIZED RAT
Authors: MARSHALL R.J. , MUIR A.W. , WINSLOW E. 
Published: July 2012

The potential use of catecholamines to increase the severity of dysrhythmias evoked by coronary artery ligation in the anaesthetized rat was investigated. Drugs were given intravenously prior to ligation.
Pressor doses of adrenaline (5 μg/kg) noradrenaline (1 μg/kg) phenylephrine (5–10 μg/kg), and angiotensin (0.25 μg/kg) conferred protection against the development of dysrhythmias.
Atropine (1 mg/kg) increased mortality from ventricular fibrilloflutter (VF) and abolished the protective effects of phenylephrine (10 μg/kg).
Administration of isoprenaline (10 μg/kg) significantly increased the incidence of and the mortality from VF.
The order of antidysrhythmic drug potency of Org 6001 (1–10 mg/kg), disopyramide (2–10 mg/kg) and practolol (2–10 mg/kg) was similar in both the standard (without isoprenaline) and modified (with isoprenaline) models.
Use of the modified method for antidysrhythmic screening purposes allows demonstration of statistically meaningful results with the use of relatively few animals.
Comparison of the pattern of VF in the rat heart induced by various means suggests that the diagnosis of ventricular fibrillation can be made with more confidence in the modified method compared to the standard method.
DISTRIBUTION AND TYPES OF ADRENOCEPTORS IN THE GUINEA‐PIG ILEUM: THE ACTION OF α‐ AND β‐ADRENOCEPTOR AGONISTS
Authors: BAUER V. 
Published: July 2012

Segments of guinea‐pig ileum and the myenteric plexus‐longitudinal smooth muscle preparation were used for a study of the actions of adrenaline, noradrenaline, isoprenaline, ephedrine and phenylephrine on the responses of coaxially stimulated ileum at different distances from the ileocaecal valve.
The responses of the ileum to electrical stimulation were suppressed by adrenaline, noradrenaline and ephedrine, while phenylephrine and isoprenaline inhibited them only partially.
The twitch inhibition elicited by these adrenoceptor agonists was the same at all distances from the ileocaecal valve. There was no significant difference between their cumulative and non‐cumulative concentration‐response curves.
Smooth muscle relaxation was induced only by isoprenaline and contraction only by phenylephrine at all distances from the ileocaecal junction. Adrenaline and noradrenaline evoked smooth muscle contraction in the terminal (0 to 20 cm), a concentration‐dependent, biphasic response in the intermediate part (21 to 50 cm) and a relaxation in the proximal ileum (>50 cm from the ilecocaecal valve). Ephedrine did not change significantly the smooth muscle tension in the terminal and the intermediate segments and induced smooth muscle relaxation in the proximal ones.
Ouabain and a potassium‐free solution did not appear to influence the prejunctional action of noradrenaline nor the amplitude of smooth muscle relaxation in the proximal ileum, whereas the concentration‐contractor response curves were significantly depressed and shifted to the right by ouabain and in a potassium‐free solution.
The brief initial (phasic) contraction induced by acetylcholine was not influenced during the sustained increase or decrease in tension induced by catecholamines. On the contrary, the stimulatory catecholamine actions disappeared or were changed to smooth muscle relaxation by acetylcholine pretreatment. Potassium chloride pretreatment did not change the character of the adrenoceptor agonist action of the agonists studied.
Since there is a similar prejunctional action at all distances from the ileocaecal valve and a different postjunctional effect of the adrenoceptor agonists at different distances from the ileocaecal junction, it could be suggested that in the guinea‐pig ileum there are at least two α‐adrenoceptors (inhibitory prejunctional‐α2, stimulatory postjunctional‐α1), an inhibitory postjunctional β‐adrenoceptor and an as yet uncharacterized inhibitory postjunctional receptor.
Based on the specific postjunctional action of phenylephrine and the prejunctional action of ephedrine in the guinea‐pig ileum, these drugs could be used with success as ‘specific’ α1 and α2‐adrenoceptor stimulants.
MECHANISM OF ACTION OF MUSCARINE ON THE LONGITUDINAL MUSCLE OF THE GUINEA‐PIG ISOLATED ILEUM
Authors: OCHILLO RICHARD F. , TSAI CHENG S. , TSAI MEI H. 
Published: July 2012

dl‐Muscarine elicited a contraction of the ileal longitudinal muscle of the guinea‐pig and the contraction was characterized by an after‐response.
Physostigmine (2.0 × 10−8 m) potentiated the contraction of the longitudinal muscle elicited by dl‐muscarine.
Hemicholinium‐3 (HC‐3) caused a rightward shift of the dose‐response curve to dl‐muscarine on the ileal longitudinal muscle of the guinea‐pig ileum.
β‐Bungarotoxin (10 μg/ml) significantly (P < 0.025) reduced the contraction elicited by dl‐muscarine (2.5 × 10−8 m) suggesting presynaptic release of acetylcholine as an indirect mechanism of action of dl‐muscarine.
Morphine (1.0 × 10−8 m) significantly (P < 0.05) reduced the contractions elicited by dl‐muscarine (2.5 × 10−8 m) further suggesting presynaptic release of acetylcholine as an indirect mechanism of action of dl‐muscarine.
A subthreshold dose of dl‐muscarine (2.0 × 10−10 m) potentiated the effect of acetylcholine (2.5 × 10−8 m) and the potentiation was blocked by β‐bungarotoxin.
DIFFERENTIAL EFFECT OF BENSERAZIDE (Ro4‐4602) ON THE CONCENTRATION OF INDOLEAMINES IN RAT PINEAL AND HYPOTHALAMUS
Authors: ARENDT J. , HO A.K. , LAUD C. , MARSTON A. , NOHRIA V. , SMITH J.A. , SYMONS A.M. 
Published: July 2012

Low doses (50 and 80 mg/kg) of benserazide (Ro4‐4602), an aromatic amino acid decarboxylase inhibitor, markedly reduced 5‐hydroxytryptamine and melatonin in the rat pineal gland without affecting hypothalamic 5‐hydroxytryptamine.
This differential effect shows that inhibition of the pineal gland decarboxylase activity is possible, and confirms that the rat pineal gland is accessible to peripherally acting agents.
CARDIOTOXIC AND INOTROPIC EFFECTS OF OUABAIN ON ATRIA ISOLATED FROM RABBITS OF DIFFERENT AGES
Authors: TODA NOBORU 
Published: July 2012

In sino‐atrial node‐right atrial preparations and left atrial preparations obtained from rabbits of different ages (2 to 360 days old), cardiotoxic and inotropic effects of ouabain were compared. Tachyarrhythmias were produced in immature and mature rabbit right atria exposed for 6 to 8 min to ouabain (5 × 10−6 m). The total number of contractions before the arrhythmias developed varied inversely with age (2 to 90 days old). Percentage reductions in the resting membrane potential, overshoot and maximum rate of rise induced by ouabain were greater in mature rabbit atria than in immature rabbit atria.
Reduction of Ca2+ in the bathing media suppressed the development of tachyarrhythmias.
In electrically‐driven left atria isolated from immature and mature rabbits, similar frequency‐contractile force curves were obtained, maximum contractions being attained at a frequency of 120/min. Ouabain at 2 × 10−7 m shifted the curve upward and at 10−6 m greatly potentiated the contractile force developed at low frequencies (6 to 30/min). Increase in contractions induced by ouabain relative to pre‐drug contractions at a frequency of 60/min were greater in immature rabbit atria (15 days old) but the positive inotropic effect of 2 × 10−7 m ouabain relative to the effect seen at 10−6 m was appreciably less.
It may be concluded that atria isolated from immature rabbits tolerate higher concentrations of ouabain than those isolated from mature rabbits.
THE GASTRIC ANTISECRETORY ACTIONS OF PROSTAGLANDIN E2 AND STABLE PROSTACYCLIN ANALOGUES AGAINST DIFFERENT SECRETAGOGUES IN PERFUSED WHOLE‐STOMACHS OF RAT OR MOUSE in vitro
Authors: BOUGHTON‐SMITH N.K. , WHITTLE B.J.R. 
Published: July 2012

The characteristics of the antisecretory actions of prostaglandin E2 (PGE2) and two stable prostacyclin analogues during different rates of acid stimulation have been evaluated in the lumen‐perfused isolated whole stomach of the rat and mouse.
In the rat isolated stomach, histamine induced a dose‐dependent increase in acid output. Preincubation with PGE2 caused a dose‐related and surmountable inhibition.
The stable prostacyclin analogues, 6β‐PGI1 and a 16‐phenoxy derivative likewise caused a surmountable inhibition of histamine‐stimulated acid output from rat stomach.
PGE2 had inconsistent actions on the acid secretion stimulated by pentagastrin, methacholine or dibutyryl cyclic adenosine 3′,5′‐monophosphate.
In the mouse isolated stomach, acid secretion was stimulated by low concentrations of histamine, pentagastrin or methacholine.
PGE2 failed to inhibit histamine‐stimulated acid output from mouse stomach, but high concentrations of the potent 16‐phenoxy analogue did show anti‐secretory activity.
The results indicate the usefulness of the rat isolated stomach for studying the interaction of prostaglandins with the acid secretory process in mammalian gastric mucosa.
EXOCYTOTIC SECRETION OF CATECHOLAMINES FROM THE CAT ADRENAL MEDULLA BY SODIUM DEPRIVATION: INVOLVEMENT OF CALCIUM INFLUX MECHANISM
Authors: NISHIMURA S. , SORIMACHI M. , YAMAGAMI K. 
Published: July 2012

Cat adrenal glands were perfused with Ca‐deficient medium and secretion of catecholamines (CA) was induced by perfusion with Na‐free medium in which NaCl was replaced by an osmotically equivalent amount of sucrose.
Release of CA and dopamine‐β‐hydroxylase (DBH), but not that of phenylethanolamine‐N‐methyltransferase, was concomitantly found in the effluents when the adrenals were stimulated, indicating that secretion was due to exocytosis.
Secretion of CA induced by Na‐free (sucrose) medium was dependent on the concentration of Ca and was saturated at 0.5 mm of Ca.
Sr or Ba substituted for Ca in maintaining secretion by Na‐free (sucrose) medium.
The addition of Na, Li or alkali metal ions to Na‐free (sucrose) medium containing Ca reduced the response to a variable extent but this inhibition was reversed by raising the concentration of Ca in the Na‐free medium.
All of the Na substitutes used induced secretion only when this medium contained Ca. However, different Na substitutes released different amounts of CA; sucrose was most effective, K, Tris and choline were moderately and Li least effective.
Secretion of CA by Na‐free (sucrose) medium was strongly inhibited by D‐600, tetracaine or divalent cations such as Co, Ni, Zn and Mg. The inhibition by Co was partially reversed by raising the concentration of Ca in the Na‐free medium.
Secretion of CA from bovine isolated chromaffin cells was induced by Na‐deficient (sucrose) medium and was dependent on the concentrations of ionized Ca involved.
All the Na substitutes tested increased secretion of CA and 45Ca uptake, in a parallel fashion.
A correlation between secretion and 45Ca uptake was found under various experimental manipulations which reduced secretion of CA.
These results demonstrated that unlike the perfused bovine adrenals, the Ca influx mechanism is essential for secretion by Na deprivation in the perfused cat adrenals as it is in bovine isolated chromaffin cells.
It is suggested that Na deprivation increases Ca entry through the Ca channels by eliminating the competition between Na and Ca, and possibly by activating Ca influx linked with Na efflux.
LIBERATION OF CATECHOLAMINES FROM BLOOD PLATELETS
Authors: PLETSCHER ALFRED 
Published: July 2012

Platelet‐rich plasma (PRP) of guinea‐pigs with or without reserpine was preincubated either with [14C]‐5‐hydroxytryptamine ([14C]‐5‐HT) plus [3H]‐dopamine or with [14C]‐5‐HT plus [3H]‐noradrenaline ([3H]‐NA). After isolation on two successive dextran gradients the double‐labelled platelets were incubated in Tris‐buffer in the presence or absence of various drugs. The decrease in radioactivity in the platelets was measured in order to determine the amount of the amine that had been liberated.
Spontaneous liberation of the labelled amines was more marked in reserpine‐treated platelets than in normal ones and somewhat more pronounced for the 3H‐catecholamines than for [14C]‐5‐HT.
The reserpine‐like benzoquinolizine, Ro 4–1284, caused liberation of all three labelled amines in normal but not in reserpine‐treated platelets. More [3H]‐dopamine was liberated than [14C]‐5‐HT and less [3H]‐NA.
The arylalkylamines, tyramine and p‐chloromethamphetamine (PCMA), liberated all three labelled amines from normal platelets, and [14C]‐5‐HT and [3H]‐dopamine, but not [3H]‐NA from reserpine‐treated ones. In normal platelets dopamine was reduced to a greater extent than [14C]‐5‐HT and [3H]‐NA to a smaller extent, whereas in reserpine‐treated platelets [14C]‐5‐HT was more markedly diminished than [3H]‐dopamine.
The 5‐HT uptake inhibitor, imipramine, had little influence on the spontaneous and drug‐induced liberation of [14C]‐5‐HT and [3H]‐dopamine.
It is concluded that 3H‐catecholamines like [14C]‐5‐HT are mostly localized in the granular pool of platelets; the three drugs tested liberate [3H]‐dopamine [3H]‐NA and [14C]‐5‐HT from the granular pool. Ro 4–1284 does not liberate 3H‐catecholamines and [14C]‐5‐HT from extragranular sites whereas tyramine and PCMA also act on the extragranular pool of [3H]‐dopamine and [14C]‐5‐HT but not [3H]‐NA.
The liberation of catecholamines from platelets differs from that of 5‐HT in several respects and platelets are only partly comparable to neurones as far as drug‐induced liberation of biogenic amines is concerned.
ELECTRICAL AND MECHANICAL ACTIVITY OF THE ISOLATED LOWER URINARY TRACT OF THE GUINEA‐PIG
Authors: CALLAHAN STEPHEN M. , CREED KATE E. 
Published: July 2012

Strips of urethra taken from guinea‐pigs contracted in response to acetylcholine, noradrenaline (via α‐adrenoceptors) and 5‐hydroxytryptamine, and were relaxed by adenosine triphosphate (ATP) if the tone was raised. Isoprenaline produced relaxation of bladder strips (via β‐adrenoceptors) whereas ATP caused contraction
Atropine completely blocked all responses to acetylcholine; quinidine failed to block ATP responses selectively; methysergide blocked responses of the urethra but not the bladder to 5‐hydroxy tryptamine
Spontaneous electrical activity was recorded with intracellular microelectrodes from all regions: in the urethra infrequent bursts of spikes occurred at 1–7 min intervals; regular spikes at 6–30/min were recorded from the detrusor muscle. In the bladder base, bursts of spikes were superimposed on the regular pattern
Bursts of spikes in the urethra were initiated by noradrenaline, phenylephrine or acetylcholine and inhibited by ATP; regular spikes in the bladder were accelerated by acetylcholine or ATP and slowed by noradrenaline or isoprenaline
The intrinsic electrical activity and pharmacological properties of the urethra therefore differ from those of the bladder. This may account for the different responses of the two regions in normal function.
COMPARATIVE STUDIES OF (−)‐, (±), (+)‐PROPRANOLOL, ATENOLOL, GUANETHIDINE, BRETYLIUM AND TETRACAINE ON ADRENERGIC TRANSMISSION
Authors: KAIHO M. , KUBO T. , MISU Y. 
Published: July 2012

Effects of (−)‐, (±)‐, and (+)‐propranolol, atenolol, guanethidine, bretylium and tetracaine were studied on relaxation responses of rabbit ileum and contractile responses of rabbit pulmonary artery and guinea‐pig vas deferens to electrical nerve stimulation (2 to 50 Hz)
In the ileum, inhibition by tetracaine 3.3 × 10−6M occurred at high frequencies of stimulation, while bretylium 1.2 × 10−4 M and guanethidine 2 × 10−5 M inhibited responses at all frequencies, the latter producing greater inhibition at low frequencies
(±)‐Propranolol 10−5 M produced a tetracaine‐type inhibition after 1 h and a bretylium‐pattern after 2 h in the ilea and pulmonary arteries and a transition from bretylium‐ to guanethidine‐pattern in the vas deferens, while atenolol 2 × 10−5 to 10−4M produced guanethidine‐type inhibition in all preparations
(−)‐, (±)‐, and (+)‐Propranolol 3 × 10−6 to 3.3 × 10−5M were equipotent in the vas deferens and ileum. However, inhibition by (−)‐propranolol 3.3 × 10−5 M persisted in the ileum, while that by the (+)‐isomer was partially restored by washing
(−)‐ or (+)‐Propranolol 3.3 × 10−5M or atenolol 2 × 10−5M did not inhibit relaxation of the ileum after the bath temperature was maintained at 4deg;C for 2 h during drug application
In conclusion, propranolol and atenolol both have gradually developing guanethidine‐like adrenergic neurone blocking actions.
EFFECTS OF CALCIUM ANTAGONISTS ON THE ALTERNATION OF THE ST‐T COMPLEX AND ASSOCIATED CONDUCTION ABNORMALITIES DURING CORONARY OCCLUSION IN DOGS
Authors: HASHIMOTO HISAKUNI , NAKASHIMA MITSUYOSHI 
Published: July 2012

The effects of Ca2+‐antagonists on the relationships between alternate changes in the ST‐T complex in the epicardial electrogram, ST‐T alternans, and associated excitation‐conduction abnormalities during coronary occlusion were examined in anaesthetized dogs
Epicardial unipolar electrograms, bipolar electrograms (BPEG) and monophasic action potentials (MAP) were recorded with unipolar, composite and suction electrodes, respectively
ST‐T alternans was associated with serious conduction delay. During the period of ST‐T alternans, the amplitude of MAP changed alternately and the negative deflection of the ST‐T complex was associated with a larger MAP. A depression of the TQ level and decrease in the resting potential of MAP were marked
Verapamil (0.2 mg/kg) and diltiazem (0.5 mg/kg) inhibited ST‐T alternans, conduction abnormalities, TQ depression and changes in MAP. However, after these drugs, the TQ depression and the decrease in the resting potential were evident after a longer period of occlusion at a time when ST‐T alternans, conduction abnormalities and alternate changes in MAP were still inhibited. Dipyridamole (0.5 mg/kg) had no effect on either ST‐T alternans or the conduction abnormalities
Verapamil and diltiazem inhibited ST‐T alternans and the associated excitation and conduction abnormalities. The effects of these two drugs cannot be explained on the basis of attenuation of the decrease in the resting potential.
EFFECTS OF VASODILATOR AGENTS ON SMOOTH MUSCLE CELLS OF THE CORONARY ARTERY OF THE PIG
Authors: ITOH T. , KAJIWARA M. , KITAMURA K. , KURIYAMA H. 
Published: July 2012

Effects of the vasodilator agents, papaverine, diltiazem, and sodium nitroprusside (SNP) on the electrical and mechanical activities of the smooth muscles of the coronary artery of the pig were compared
At a concentration of 10−5 M, papaverine hyperpolarized and increased the ionic conductance of the membrane, SNP slightly hyperpolarized but diltiazem had no effect on the membrane potential and membrane ionic conductance
At a concentration of 10−5 M, diltiazem abolished the spike evoked by outward current pulses in the presence of tetraethylammonium (TEA) 10 mM, while papaverine and SNP slightly reduced spike amplitude
The K‐induced contraction produced by any given concentration of [K]o over 20.2 mM was suppressed by diltiazem and SNP dose‐dependently in concentrations greater than 10−6m; higher concentrations of papaverine were required to suppress contraction
The acetylcholine (ACh)‐induced contraction was suppressed by diltiazem and SNP at concentrations greater than 10−6 M and by papaverine in concentrations over 10−5 M
In saponin‐treated skinned muscles, papaverine, diltiazem and SNP had no effect on the pCa‐tension relationship, i.e. these agents had no effect on the Ca receptor of contractile proteins. Furthermore, the caffeine‐induced contraction in skinned muscles (after Ca loading) was not affected by these agents, i.e. the mechanism of Ca release by caffeine in skinned muscles was not affected
Chlorpromazine, an agent interacting with calmodulin, antagonized the contractile effect of calcium on skinned muscle fibres
The results obtained are discussed in relation to spike and contraction generating mechanisms, i.e. the effects of these agents on Ca influx and Ca release from stored sites. The results indicated that at equimolar concentrations diltiazem suppressed the mechanical response in the coronary artery of the pig more than SNP or papaverine.