bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of prostaglandin E2 on fast and slow components of the response of the rat vas deferens to field stimulation
Authors: Bedwani J.R. , Blanning P.E. 
Published: July 2012

The response of the rat vas deferens to field stimulation with single pulses is biphasic. The first, rapid component of the response is dominant at the prostatic end and is thought by some to be mediated by non‐adrenergic, non‐cholinergic neurotransmission. The second, slower component predominates at the epididymal end and has the usual properties associated with adrenergic responses.
Prostaglandin E2 (PGE2, 10−8 to 10−5 mol/l) inhibited the ‘fast component’ responses elicited by field stimulation of the prostatic vas from reserpine‐treated rats. The prostaglandin was more potent in the presence of 1.25 than 2.5 mmol/l Ca2+.
PGE2 (10−7 to 10−5 mol/l) had similar effects on prostatic preparations from normal rats, but was less active on these.
PGE2 (10−9 to 10−5 mol/l) did not inhibit the ‘slow component’ responses resulting from field stimulation of the epididymal vas but rather, at the two highest concentrations used (5 × 10−6 and 10−5 mol/l), potentiated them. These high concentrations of the prostaglandin also potentiated the contractions of the epididymal vas elicited by exogenous noradrenaline.
These effects of PGE2 on the two components of the response of the rat vas deferens are not as might be expected from its inhibitory effects on the ‘typical’ adrenergic neurotransmission in several other sympathetically‐innervated tissues.
Effects of antiarrhythmic drugs on ventricular fibrillation thresholds of normal and ischaemic myocardium in the anaesthetized rat
Authors: Marshall R.J. , Muir A.W. , Winslow E. 
Published: July 2012

The effects of agents which produce membrane stabilization (class I), β1‐adrenoceptor blockade (class II), prolongation of the cardiac action potential (class III) or inhibition of the slow inward current (class IV) were investigated for their ability to increase the ventricular fibrillation threshold (VFT) or to modify the fall in VFT consequent upon coronary artery ligation in the anaesthetized rat.
The class I agent, Org 6001, increased VFT of normal myocardium and in lower doses reduced the postligation fall in VFT.
The class II agent, metoprolol, failed to increase VFT of normal myocardium but reduced the postligation fall.
The class III agent, melperone, increased VFT of both normal and ischaemic myocardium whereas the class IV agent, nifedipine failed to influence VFT in either region.
Bepridil (class I and IV) was similar to Org 6001 and sotalol (class II and III) in that it increased VFT of normal myocardium and in lower doses reduced the postligation fall in VFT.
Measurement of VFT before and after coronary artery ligation in the rat constitutes a rapid and reproducible screen to detect antifibrillatory activity.
The results also suggest that in the rat, the low currents used (˜400 μA) do not release substantial quantities of catecholamines whereas these may be released by coronary artery ligation.
The effect of an inhibitory factor from the bovine retractor penis on the gastro‐intestinal tract and gall bladder of the guinea‐pig
Authors: Crossley A.W.A. , Gillespie J.S. 
Published: July 2012

The effect of a smooth muscle inhibitory factor extracted from the bovine retractor penis has been examined on a variety of in vitro smooth muscle preparations from the guinea‐pig alimentary canal and on the guinea‐pig gall bladder.
The inhibitory factor caused relaxation of spontaneous and carbachol‐induced tone in the taenia coli, the stomach fundal strip and the duodenum and colon. There was little effect on the ileum. Sensitivity was highest in the taenia coli where the response to the inhibitory factor mimicked the response to stimulation of the non‐adrenergic, non‐cholinergic (NANC) inhibitory nerves.
In the taenia coli the inhibitory response to stimulation of the NANC nerves and to ATP was abolished by apamin 5 × 10−8 m, whereas this or higher concentrations had no effect on the response to the inhibitory factor. This makes it unlikely that the latter is the neurotransmitter in these NANC nerves.
The inhibitory factor had no effect on the gall bladder. Inhibitory responses to field stimulation were obtained in this tissue but these were insensitive to tetrodotoxin in concentrations greater than those needed to block the motor cholinergic nerves.
Thyrotropin releasing hormone‐induced hyperthermia in mice: possible involvement of adrenal and pituitary glands
Authors: Boschi Gabrielle , Nomoto Teruko , Rips Richard 
Published: July 2012

To investigate the hyperthermic effect of thyrotropin releasing hormone (TRH) and its potentiation by exogenous catecholamines (CA), the role of the adrenal medulla and of the pituitary gland was studied in unoperated, adrenal‐demedullated or hypophysectomized mice.
In unoperated mice, TRH 40 mg kg−1 i.p. produced a hyperthermia which was accompanied by an increase in plasma noradrenaline (NA) and adrenaline (Ad). NA or Ad, both at a dose of 1 mg kg−1 i.p., enhanced the TRH‐induced hyperthermia.
Adrenal demedullation suppressed the hyperthermia and the increase of plasma CA produced by TRH but not the potentiation of this hyperthermia by exogenous CA.
Hypophysectomy abolished the TRH‐induced hyperthermia but not the increase of plasma CA or the potentiation of this hyperthermia by exogenous CA.
These results suggest that, in mice, both the adrenal medulla and the pituitary gland play an essential role in TRH‐induced hyperthermia but not in its potentiation.
Hypoxia‐induced cardiac hypertrophy in rabbits treated with verapamil and nifedipine
Authors: Dukes I.D. , Williams E.M. Vaughan 
Published: July 2012

Young rabbits were exposed, eight at a time, to 310 h of hypoxia (O2 at 70–80 torr), at atmospheric pressure. The animals were injected with 1 mg kg−1 nifedipine (F) or 5 mg kg−1 verapamil (V) or an equivalent volume of the vehicle (H) (Cremophor EL), i.p. twice a day. A fourth group (N), also injected with vehicle, was not made hypoxic.
The animals were from 6 litters, 6 rabbits in each litter, and were distributed so that every group had litter mates in the other groups.
Right ventricular hypertrophy was induced in all the hypoxic groups (H, + 39%; V, + 46%; F, + 44%). Differences between groups were not statistically significant, but all were significantly hypertrophied relative to their normoxic litter mates (N). The right atria were less hypertrophied (H, + 3.6%; V, + 20%; F, + 21.6%), but there was no left ventricular or left atrial hypertrophy.
There was also a small increase in haematocrit in the hypoxic groups (H, + 20.6%; V, + 17.5%; F, + 28.8%).
The doses administered were equivalent to the highest used clinically producing blood levels of verapamil and nifedipine within or above the clinical range and had no effect on the development of cardiac hypertrophy.
Effects of increasing the frequency of twitches and of isoprenaline on maximal twitches and cyclic AMP levels in slow‐ and fast‐contracting cat skeletal muscles
Authors: Merican Zainuddin , Nott M.W. , Sunbhanich M. 
Published: July 2012

Increasing the frequency of twitches and treatment with isoprenaline have been been compared for effects on twitch tension, tension‐time integral and cyclic adenosine 3′, 5′‐monophosphate (cyclic AMP) levels in the slow‐contracting soleus muscle of cats, anaesthetized with chloralose and pentobarbitone. The effect of change in frequency of contractions on cyclic AMP in the fast‐contracting extensor digitorum longus muscle was also examined.
Although both isoprenaline and increasing the frequency of contractions depressed twitch tension in the soleus, only isoprenaline enhanced cyclic AMP levels. The effects of isoprenaline were independent of the existing frequency of contractions of the muscle. Increasing the frequency of contractions enhanced twitches in the extensor digitorum longus muscle but did not change cyclic AMP levels.
It is concluded that cyclic AMP may mediate effects of β‐adrenoceptor agonists but not those caused by increasing the frequency of contractions on slow‐ or fast‐contracting skeletal muscles.
Effects of cyproheptadine on electrophysiological properties of isolated cardiac muscle of dogs and rabbits
Authors: Neto Francisco Riccioppo 
Published: July 2012

The effects of cyproheptadine were studied on cardiac Purkinje and ventricular muscle fibres of the dog and on cells of the sinoatrial (SA) node region of rabbit hearts, by means of electrophysiological techniques.
Cyproheptadine (2–8 μm) decreased, in a dose‐dependent manner, the plateau amplitude and the action potential duration to 50% repolarization of Purkinje and ventricular muscle cells. Higher concentrations also depressed the action potential amplitude, the overshoot and the maximum rate of rise of the upstroke. These effects were only partially reversed on washing.
A four fold increase in Ca concentration of the standard Tyrode solution antagonized the effects of cyproheptadine on the action potential characteristics.
The ‘slow response’ obtained in K‐depolarized isoprenaline‐treated fibres was blocked by cyproheptadine (4 μm).
Cyproheptadine (10 μm) depolarized and suppressed the automaticity of spontaneously beating Purkinje fibres.
The frequency of discharge of the SA node cells was slowed or abolished by cyproheptadine (2–4 μm). Atropine (2.6 μm) did not affect the negative chronotropic effect, whereas adrenaline (5 μm) reversed it.
It is suggested that cyproheptadine depresses the slow inward current in all types of myocardial fibres studied. Higher concentrations might also affect the fast inward sodium current system.
Demonstration of α1s‐adrenoceptors after exposure of the rat anococcygeus to benextramine
Authors: Coates Jill , Weetman D.F. 
Published: July 2012

Sgd 101/75 (4(2‐imidazoline‐amino)‐2‐methylindazol‐chlorhydrate) and noradrenaline exerted similar, full agonist effects on the α‐adrenoceptors of the rat anococcygeus.
Benextramine (30 μm for 30 min, followed by 20 washes over 30 min) abolished contractions of the anococcygeus to Sgd 101/75, but only reduced those to noradrenaline.
Sgd 101/75 (400 μm) did not significantly reduce contractions of the benextramine‐treated (30 μm) anococcygeus to noradrenaline.
It is concluded that benextramine can replace phenoxybenzamine as the alkylating agent in the demonstration of α1s‐adrenoceptors in the rat anococcygeus.
Two distinct interactions of barbiturates and chlormethiazole with the GABAA receptor complex in rat cuneate nucleus in vitro
Authors: Harrison N.L. , Simmonds M. A. 
Published: July 2012

Some pharmacological properties of the GABAA receptor complex in the rat cuneate nucleus slice have been assessed from depolarization responses to the γ‐aminobutyric acid (GABA) analogue muscimol and antagonism of the responses by bicuculline and picrotoxin.
Responses to muscimol were potentiated by the following drugs, in descending order of potency with regard to the concentrations required in the Krebs medium: (±)‐5‐(1,3‐dimethylbutyl)‐5‐ethylbarbituric acid ((±)‐DMBB) = (±)‐quinalbarbitone = (± pentobarbitone > (±)‐methyl‐phenobarbitone = (−)‐methylphenobarbitone > butobarbitone = chlormethiazole > phenobarbitone > barbitone = (+)‐methylphenobarbitone. Primidone and phenylethylmalonamide were inactive. Calculation of the concentrations likely to be present in membrane lipids for equal potentiations of muscimol revealed little difference between quinalbarbitone, pentobarbitone, phenobarbitone and barbitone.
The effect of picrotoxin as a muscimol antagonist was selectively reduced only by DMBB, chlormethiazole, phenobarbitone and (−)‐methylphenobarbitone in concentrations that caused only a modest potentiation of muscimol.
It is suggested that a specific site of action in the GABAA receptor complex is involved in the reduction of picrotoxin effect and that this may be relevant to the anticonvulsant properties of chlormethiazole, phenobarbitone and (−)‐methylphenobarbitone. The potentiation of muscimol by chlormethiazole and the barbiturates in general involves a distinctly different site that is less selective and this may underlie the hypnotic properties of these drugs.
Conversion of prostacyclin to 6 oxo prostaglandin E1 by rat, rabbit, guinea‐pig and human platelets
Authors: Griffiths R.J. , Moore P.K. 
Published: July 2012

The enzymatic catabolism of prostacyclin (PGI2) to 6 oxo prostaglandin E1 (6 oxo PGE1) was studied in platelet‐rich and platelet‐poor‐plasma of rat, rabbit, guinea‐pig and man.
Rat, rabbit and human platelets convert PGI2 to a product with biological activity and thin layer chromatographic mobility identical to that of authentic 6 oxo PGE1. Platelets from these species also converted 9β‐[3H]‐PGI2 to non‐radioactive 6 oxo PGE1 as shown by the progressive loss of extracted radioactivity following incubation. Formation of 6 oxo PGE1 was inhibited by the flavonoid drugs, rutin and naringenin.
Guinea‐pig platelets did not convert PGI2 to 6 oxo PGE1.
Rat, rabbit and guinea‐pig platelets do not spontaneously release a 6 oxo PGE1‐like substance when incubated at 37°C in the absence of added PGI2 or aggregating agents.
The relevance of these findings to the possible physiological and pathophysiological roles of 6 oxo PGE1 in the regulation of platelet function is discussed.
A comparison of adenine and some derivatives on pig isolated tracheal muscle
Authors: Bach‐Dieterle Yvonne , Holden William E. , Junod Alain F. 
Published: July 2012

We studied the muscle relaxation induced by adenine and several adenine derivatives in strips of tracheal smooth muscle from pigs; in addition their metabolism by the tissue was examined.
Adenine relaxed tissue which was contracted by carbachol, histamine, or KCl. Adenine's potency was similar to that of adenosine and ATP (threshold about 4 × 10−5 m).
In tissues with carbachol‐induced tone, the adenine effect differed from adenosine and ATP by being slower in onset and in ‘washout’ time. Furthermore, neither dipyridamole nor theophylline modified the response to adenine.
The relationship was examined between pharmacological effects and the metabolism of [3H]‐adenosine and [3H]‐adenine. Both substrates were taken up by the tissue and converted to nucleotides, but relaxation correlated with nucleotide accumulation only in the case of [3H]‐adenine.
We conclude that the site and mechanism of adenine‐induced relaxation is different from that of adenosine and ATP in porcine tracheal muscle.
Inhibition by propranolol of the contractile response of the rat diaphragm to tetanic field stimulation in vitro
Authors: Drazen Jeffrey M. , Lacouture Peter G. , Miller Michael J. 
Published: July 2012

Contraction of the rat isolated diaphragm in response to maximal tetanic stimulation was examined before and after isoprenaline or propranolol.
Isoprenaline (10−4m) did not affect maximum isometric force, whereas propranolol depressed maximum force in a concentration‐dependent manner (10−6‐10−4m).
Inhibition due to propranolol (10−4m) could not be overcome by increasing the intensity or duration of electrical stimulation, and was only partially reversed (mean 73% ± 10 s.e.mean) after washing.
Pretreatment with isoprenaline did not alter the response of the muscle to propranolol, nor did neuromuscular blockade with (+)‐tubocurarine.
The response to either stereoisomer of propranolol was similar to that obtained with the racemate.
Atenolol, a β‐adrenoceptor blocking agent without membrane stabilizing activity, had minimal (< 10%) depressant effects on diaphragmatic force development.
Lignocaine (8.5 × 10−6‐8.5 × 10−5m) produced a concentration‐related decrease in isometric force, similar to that with propranolol.
It is concluded that propranolol decreases the contractile force of the rat isolated diaphragm by a mechanism related to stabilization of excitable membranes.
Characterization of adenosine receptors in isolated cerebral arteries of cat
Authors: Edvinsson Lars , Fredholm Bertil B. 
Published: July 2012

The effect of some adenosine analogues and xanthine derivatives were studied on isolated cerebral arteries from cats.
The adenosine analogues caused an almost complete relaxation of cerebral arteries contracted by prostaglandin F2α (PGF2α, 30 μm). The order of potency was: 5‐N‐ethylcarboxamide adenosine (NECA) > 2‐chloroadenosine > adenosine > l‐N6‐phenylisopropyl adenosine (l‐PIA). The analogue d‐PIA was very weak and its maximum effect was small.
NECA and l‐PIA enhanced [3H]‐cyclic AMP accumulation in [3H]‐adenine labelled feline pial vessels with similar absolute and relative potency to their relaxant effects.
The relaxant effects of adenosine and of NECA were competitively antagonized by 8‐phenyl‐theophylline (pA2 = 6.5). The effect of theophylline and enprofylline could not be tested in higher concentrations than 30 or 10 μm because they affected the vessels directly. At these concentrations they were essentially inactive as adenosine antagonists. The non‐xanthine phosphodiesterase inhibitor rolipram (0.1 and 100 μm) caused a slight but non‐significant potentiation of the relaxant effect of adenosine.
The results are compatible with the opinion that adenosine relaxes cerebral vessels by an action on adenosine A2‐receptors. The effect may be linked to adenylate cyclase and can be antagonized by 8‐phenyl‐theophylline.
Pharmacological characterization of the inhibitory effects of neurotensin on the rabbit ileum myenteric plexus preparation
Authors: Huidobro‐Toro J.Pablo , Yoshimura Kohji 
Published: July 2012

Neurotensin in picomolar concentrations caused a concentration‐related inhibition of the spontaneous contractile activity of the longitudinal muscle from the rabbit isolated ileum. Neurotensin was approximately 100 times more potent than adrenaline and about 10000 times as active as adenosine triphosphate (ATP) in producing similar relaxations.
The neurotensin‐induced inhibitory effect did not follow activation of adrenoceptors or P1‐purinoceptors since the effect of the neuropeptide was not antagonized by a combination of phentolamine plus (−)‐propranolol, nor by pretreatment with theophylline.
Tetrodotoxin did not reduce the potency of neurotensin in relaxing the rabbit ileum, suggesting that the neurotensin‐induced inhibition is not neuronally mediated. The inhibitory responses of neurotensin were blocked non‐competitively by apamin.
The inhibitory effect of neurotensin was short‐lived with the subsequent development of tachyphylaxis, which was not crossed to the inhibitory action of adrenaline or ATP. Similarly, when tachyphylaxis to adrenaline or to ATP was established, the inhibitory action of neurotensin was unaffected. Desensitization was characterized by a gradual shift of the neuropeptide concentration‐response curve to the right and downwards.
Preincubation of rabbit ileum strips with 10 nm dynorphin (1–13) significantly increased the inhibitory action of neurotensin.
The use of neurally released agonist in the measurement of antagonism at α‐adrenoceptors
Authors: French Andrew M. , Scott Neil C. 
Published: July 2012

Graded contractile responses of the rat vas deferens were obtained to trains containing varying numbers of pulses delivered transmurally at 500 Hz, allowing construction of pulse‐response curves.
In the presence of postjunctional adrenoceptor blocking drugs, these curves were displaced to the right in a parallel manner, allowing the estimation of pA2 values for the drugs.
Activity of drugs at prejunctional adrenoceptors was estimated from the reduction of inhibition of the response to a second pulse delivered 3 s after trains containing different numbers of pulses.
It is suggested that the technique is more physiological than others used to determine the antagonistic activity of drugs at adrenoceptors.
Effect of desamino‐cholecystokinin‐octapeptide (CCK‐7) on the intraluminal pressure and myoelectrical activity of the gall‐bladder, stomach, and small intestine in conscious dogs
Authors: Milenov E. , Nieber K. , Niedrich H. , Oehme P. , Vogt W.‐E. 
Published: July 2012

Desamino‐cholecystokinin‐octapeptide (CCK‐7) increased the gall‐bladder pressure and decreased the gastric pressure following i.v. infusion in conscious dogs.
In small intestine and Heidenhain pouch CCK‐7 exerted an initial excitatory effect followed by an inhibitory effect on intraluminal pressure and peristalsis.
In all organs the effect of CCK‐7 on pressure was correlated with a change of spike discharge.
CCK‐7 is more potent on gastrointestinal motor activity than a Boots preparation of pancreozymin.
The results suggest that CCK‐7 at doses within the physiological range could be involved in the regulation of gastrointestinal motility.
Heterogeneity of 5‐hydroxytryptamine receptors in the rat uterus and stomach strip
Authors: Wrigglesworth Susan J. 
Published: July 2012

Experiments were performed using the rat isolated uterus and the rat stomach strip to investigate the effects of 5‐hydroxytryptamine (5‐HT) on 5‐HT receptors in the presence of different antagonists. Amitriptyline, methysergide and trazodone were used to antagonize the response to 5‐HT in these tissues.
The pA2 value for amitriptyline with 5‐HT as the agonist was estimated from the Schild plot analysis and found to differ significantly (P<0.05) in the stomach strip (6.36) from that in the isolated uterus (9.06).
A similar difference was found using trazodone; here the pA2 value was 6.74 in the stomach strip and 8.49 in the isolated uterus.
These results indicate a difference between the two tissues. This difference is discussed in terms of heterogeneity of 5‐HT receptors.
Antagonism of enkephalin action on acetylcholine release by methylxanthines: lack of a purine link
Authors: Elliott Janet , Jhamandas Khem , Notman Holly , Sutak Maaja 
Published: July 2012

Theophylline (Theo) and caffeine antagonized the inhibitory effect of methionine (Met)‐enkephalin, leucine (Leu)‐enkephalin and morphine on the twitch height of the field stimulated myenteric plexus longitudinal muscle (MPLM) preparation of the guinea‐pig ileum. Antagonism by Theo was observed only in tissues stimulated submaximally, but that by caffeine was observed in tissues stimulated submaximally and supramaximally.
Injection of Theo (20, 40 mg kg−1) or caffeine (40 mg kg−1) reversed or blocked the inhibitory effects of Leu‐enkephalin (50 μg i.c.v.) and a systemically active enkephalin FK 33,824 (0.5 mg kg−1) on the release of acetylcholine (ACh) from the rat cortex in vivo.
Injections of morphine (2.5, 5.0 mg kg−1 i.v.) did not modify the in vivo release of radiolabeled purines from the cerebral cortex prelabelled with [3H]‐adenosine (2.8 × 10−7 m). Application of K+ (60 mm) to the cortex readily stimulated this release. Injection of morphine (5.0 mg kg−1 i.v.) increased the spontaneous release of radiolabeled purines from the cortex prelabelled with a higher concentration of [3H]‐adenosine (10−4 m) in six out of eleven experiments. Under similar conditions neither Leu‐enkephalin (50 μg i.c.v.) nor FK 33,824 (0.5 mg kg−1 i.v.) stimulated purine release.
It is concluded that methylxanthines can antagonize the inhibitory action of opioids on the peripheral and central release of ACh. However, this antagonism does not reflect an intermediary purine step in the action of opioids on the release of ACh.