bluuebunny/crossref_metadata_2025_split huggingface dataset:
METABOLISM OF ARACHIDONIC ACID AND ITS ENDOPEROXIDE (PGH2) TO MYOTROPIC PRODUCTS IN GUINEA‐PIG AND RABBIT ISOLATED LUNGS
Authors: ALABASTER VALERIE A. 
Published: July 2012

Conversion of arachidonic acid (AA) and its endoperoxide (PGH2) to myotropic metabolites has been studied in isolated Krebs‐perfused lungs of guinea‐pig and rabbit. A continuous differential bioassay technique was used to measure myotropic metabolites in the lung perfusate.
AA was metabolized in guinea‐pig lungs to thromboxane A2 (TxA2), prostacyclin (PGI2) and small amounts of a prostaglandin E2 (PGE2)‐like substance. The amounts of products were dose‐related over the AA range used (1 to 10 μg). PGH2 was detected only after AA (10 μg).
Rabbit lungs converted AA (2.5 to 10 μg) to the same products in similar relative proportions but the amounts were 15 to 25% of those produced by guinea‐pig lungs.
Indomethacin (10 nm) preferentially inhibited metabolism of AA to prostaglandins in guinea‐pig lungs but preferentially inhibited metabolism to TxA2 in rabbit lungs. Higher concentrations (50 nm) greatly reduced conversion to all the myotropic metabolites in lungs from both species.
Imidazole (50 μm) selectively inhibited conversion of AA to TxA2 and increased conversion to PGI2 in rabbit lungs. A similar effect was produced in guinea‐pig lungs but with much higher concentrations of imidazole (2.5 to 5 mm).
PGH2 (800 ng) was converted in guinea‐pig lung to TxA2 (100 ng) and very small amounts of PGI2 (10 to 16 ng) but only unchanged PGH2 and some PGE2 were present in the lung perfusate after injection of PGH2 in rabbit lung.
It is concluded that guinea‐pig and rabbit lung differ in their ability to metabolize AA to myotropic substances and also in their response and sensitivity to drugs which interfere with prostaglandin and TxA2 synthesis. The lungs do not appear to have an important role in converting PGH2 to PGI2.
THE EFFECTS OF SENSORY DENERVATION ON THE RESPONSES OF THE RABBIT EYE TO PROSTAGLANDIN E1, BRADYKININ AND SUBSTANCE P
Authors: BUTLER J.M. , HAMMOND B.R. 
Published: July 2012

Six to eight days after diathermic destruction of the fifth cranial nerve in the rabbit, the ocular hypertensive and miotic responses to intracameral administration of capsaicin, bradykinin, and prostaglandin E1 were greatly reduced or completely abolished. The response to substance P was not abolished.
A response could still be obtained to chemical irritants 36 h after coagulation of the nerve and it is deduced that manifestation of the response is dependent upon functional sensory nerve terminals, and is independent of central connections.
It is suggested that prostaglandin E1 and bradykinin act directly upon the sensory nerve endings and that propagation of the response is augmented by axon reflex.
In view of the ability of substance P to induce miosis in the denervated eyes, it is presumed that its actions are not mediated via sensory nerves.
It is considered possible that the mediator(s) released from sensory nerve endings after chemical irritation or antidromic stimulation may act in the same way as substance P with regard to the miotic effect.
Synthetic substance P will only produce ocular hypertension in doses which induce a maximal miotic response. This may either be a question of access or a partial resemblance to the endogenous mediator.
SUBSENSITIVITY TO CHOLINOCEPTOR STIMULATION OF THE HUMAN IRIS SPHINCTER in situ FOLLOWING ACUTE AND CHRONIC ADMINISTRATION OF CHOLINOMIMETIC MIOTIC DRUGS
Authors: SMITH SHIRLEY A. , SMITH S.E. 
Published: July 2012

Maximal pupillary miosis was obtained with single topical applications of 4 cholinomimetic drugs in therapeutic concentrations to normal human subjects.
When the pupil had recovered from the miosis, there remained a reduced light reflex response of 22.7% at 24 h after aceclidine, 18.0% at 31 h after pilocarpine, 10.3% at 48 h after physostigmine and 4.9% at 7 h after arecoline.
This reduced sensitivity to light was accompanied by an overshoot of the resting pupil diameter and, after aceclidine miosis, a reduced response to a second application of miotic.
Similar findings were observed in glaucoma patients following withdrawal of chronic pilocarpine therapy.
It is suggested that the slowly reversible after‐effects of acute and chronic administration of cholinomimetic miotics can be explained by desensitization of iris sphincter cholinoceptors.
EFFECTS OF THYROTROPHIN‐RELEASING HORMONE, AND METHIONINE‐ENKEPHALIN ON GASTRIC ACID AND PEPSIN SECRETION IN THE CAT
Authors: GASCOIGNE A.D. , HIRST B.H. , REED J.D. , SHAW B. 
Published: July 2012

The effect of intravenous administration of thyrotrophin‐releasing hormone (TRH) and methionine‐enkephalin on gastric acid and pepsin secretions was investigated in conscious cats prepared with chronic gastric fistulae.
TRH, 20 μg kg−1 h−1, did not influence unstimulated gastric acid secretion, nor gastric acid secretion stimulated by submaximal doses of pentagastrin or histamine. Pepsin secretion stimulated by pentagastrin was not influenced by TRH.
TRH, 20 μg kg−1 h−1, significantly reduced the gastric acid and pepsin responses to intravenous infusion of insulin. TRH also significantly reduced the degree of hypoglycaemia seen in response to insulin. TRH, 20 μg kg−1 h−1, but not 5 μg kg−1 h−1, infused alone resulted in a significant hyperglycaemia.
It is concluded that the reduction of insulin‐stimulated gastric secretion by TRH is not dependent on the hyperglycaemic action of the peptide. The mechanism of action of TRH on insulin‐stimulated secretion is discussed with respect to its site of action.
Methionine‐enkephalin or the potent analogue, d‐Ala2, Met‐enkephalinamide were without effect on unstimulated gastric secretion, or secretion stimulated by pentagastrin, histamine, and insulin. The opiate receptor antagonist, naloxone, did not significantly alter the gastric acid or pepsin response to insulin.
It is concluded that there is no evidence that opiates stimulate oxyntic glands directly, nor that the oxyntic cells may possess high affinity binding sites for opiates, nor that endogenous opiates are involved in the control of gastric secretion.
OBSERVATIONS ON CHLORALOSE‐INDUCED MYOCLONUS IN GUINEA‐PIGS
Authors: CHADWICK D. , HALLETT M. , JENNER P. , MARSDEN C.D. 
Published: July 2012

The physiological, biochemical and pharmacological features of α‐chloralose‐induced myoclonus in the guinea‐pig have been studied.
EMG bursts in muscles jerking in chloralose‐induced myoclonus are long, and are not time‐locked to any cortical event recorded in the EEG, although they are evoked by auditory or peripheral nerve stimuli.
The efferent conduction velocity down the spinal cord of the signals generating the EMG bursts is fast but the afferent conduction velocity up the cord for stimulus‐evoked jerks is slow, in distinction to the reverse characteristics of the spino‐bulbo‐spinal reflex arc.
α‐Choralose did not cause any consistent change in 5‐hydroxytryptamine (5‐HT) or 5‐hydroxy‐indoleacetic acid levels in any brain area, nor did it alter 5‐HT turnover as judged by the depletion of 5‐HT after p‐chlorophenylalanine pretreatment.
Pretreatment of animals with drugs that increase brain 5‐HT action (l‐tryptophan with a monoamine oxidase inhibitor, or 5‐hydroxytryptophan), or antagonize the action of 5‐HT (cyproheptadine) did not abolish or obviously increase chloralose‐induced myoclonus.
Chloralose‐induced myoclonus is not similar to 5‐HT‐sensitive reticular reflex myoclonus in man.
ADAPTATIONAL RESPONSES TO PROLONGED β‐ADRENOCEPTOR BLOCKADE IN ADULT RABBITS
Authors: RAINE A.E.G. , WILLIAMS E.M. VAUGHAN 
Published: July 2012

A method for measuring propranolol concentrations in plasma has been modified to permit estimations to be made on small volumes. The method has been used to correlate blockade of heart rate increases in response to intravenous isoprenaline, in both young and adult rabbits, with plasma concentrations of propranolol after subcutaneous injections of 2 or 4 mg/kg. It has been found that the relation between β‐adrenoceptor blockade and plasma concentrations is the same in rabbits as that determined by previous workers in man.
Adult Dutch dwarf rabbits were treated for 9 weeks twice daily subcutaneously with 2 mg/kg propranolol, or 10 mg/kg practolol, or with saline.
The treatment caused no change in heart weight in relation to body weight or in the water content of the hearts, in contrast to effects previously observed in young rabbits.
As in the young rabbits, treatment did cause a prolongation of action potential duration, as measured with intracellular electrodes in hearts of animals killed 24 h after the last dose of drug.
In another series of experiments, with a similar regime of treatment for 6 weeks, a significant reduction of diastolic blood pressure was observed in the propranolol group.
During the course of treatment and at the end, there was no change in the heart‐rate increases observed in response to intravenous isoprenaline administered not less than 15 h after the previous dose of β‐blockers. Thus no functional alteration in sensitivity to β‐adrenoceptor stimulation was apparent.
EVIDENCE FOR MULTIPLE SOURCES OF CALCIUM FOR ACTIVATION OF THE CONTRACTILE MECHANISM OF GUINEA‐PIG taenia coli ON STIMULATION WITH CARBACHOL
Authors: BRADING ALISON F. , SNEDDON P. 
Published: July 2012

The evidence presented suggests there are three sources of Ca available for contraction of the smooth muscle of the guinea‐pig taenia coli on stimulation with carbachol; the inward Ca current of the spike, a second voltage‐dependent Ca channel and an internal Ca store.
The initial increment of tension in response to carbachol is thought to be due to an increase in spike frequency which is probably the main source of Ca at low carbachol concentrations (< 10−6 m).
The maintained tension in the continuous presence of high concentrations of carbachol seems to involve continuous influx of membrane‐bound Ca by a potential‐dependent mechanism which can be very quickly deactivated, resulting in rapid relaxation. This mechanism can be blocked by 2 × 10−7 m methoxyverapamil (D600).
An internal Ca store can be released by high concentrations of carbachol (<10−6 m) and is probably responsible for the initial transient peak of tension, of about 5 min duration seen on continuous application of high concentrations of carbachol and for the tension increase in response to carbachol in tissues depolarized in high‐K.
Investigation of the properties of the store indicates that it; (i) is very rapidly filled by application of high extracellular Ca; (ii) empties after a few minutes in zero‐Ca EGTA Krebs solution; (iii) can be refilled in depolarized tissues in the presence of low concentrations of D600 and Mn, but does not refill during application of carbachol at concentrations greater than 10−6 m; (iv) contains enough Ca for one near‐maximal contraction and once emptied can assist relaxation by Ca re‐uptake.
IMIPRAMINE NORMALIZES NATURALLY‐OCCURRING AND DRUG‐INDUCED DIFFERENCES IN THE EXPLORATORY ACTIVITY OF RATS
Authors: HARRISON‐READ P.E. , STEINBERG HANNAH 
Published: July 2012

Exploratory activity of female hooded rats was measured in a Y maze on two occasions, 1 week apart. Locomotion (maze arm entries), rearing, and head‐dipping into pots were scored for 5 min at each trial.
In control rats, differences between individuals in the amount of locomotion and rearing were consistent, as shown by significant test‐retest correlations (r = +0.55, and +0.83 respectively). There was no correlation between head‐dipping scores obtained in the two tests.
Imipramine (Imip) pretreatment before the second trial (10 mg/kg i.p. on the 3 preceding days, and 2.5 mg/kg 1 h before) abolished these correlations. The scatter of the scores about the mean was also reduced by Imip, but there was no significant change in mean scores. Thus Imip appeared to have a ‘normalizing’ effect on locomotion and rears: after pretreatment, scores tended to be more uniform, and no longer reflected naturally‐occurring individual differences.
Imip abolished the changes in exploratory activity produced by drugs which alter brain 5‐hydroxytryptamine metabolism: p‐chlorophenylalanine (100 mg/kg 24 h before testing) increased and dl‐5‐hydroxytryptophan (12.5 mg/kg 1 h before testing) decreased the fall in activity over the trial in saline‐treated rats but not that in Imip‐treated rats. In this case, Imip also produced an overall reduction in activity scores.
The normalizing effects of Imip on rat behaviour may be analogous to its therapeutic effects in human depressive disorders.
THROMBOXANE B2 INHIBITS THE PULMONARY INACTIVATION OF PROSTAGLANDIN E2 IN THE DOG
Authors: FITZPATRICK THOMAS M. , FRIEDMAN LAWRENCE S. , KOT PETER A. , RAMWELL PETER W. 
Published: July 2012

The systemic vasodepressor response to intravenously administered prostaglandin E2 (PGE2, 0.3, 1.0 and 3.0 μg/kg) is potentiated during intravenous infusion of thromboxane B2 (TXB2, 1.0 μg kg−1 min−1) in the anaesthetized dog.
The augmented haemodynamic response returns toward control values following cessation of the TXB2 infusion.
The systemic haemodynamic responses to intra‐arterially administered PGE2, PGF2α and PGI2 as well as intravenously administered PGF2α and PGI2 are not altered by TXB2 infusion.
This study suggests that TXB2 inhibits the pulmonary inactivation of PGE2.
Arachidonic acid metabolites may interact, producing haemodynamic responses differing from their individual effects.
RELATION BETWEEN CALCIUM AND CARDIOVASCULAR REACTIVITY IN MINERALOCORTICOID‐INDUCED HYPERTENSION IN THE RAT
Authors: BERTHELOT A. , GAIRARD A. , GOYAULT M. , PERNOT F. 
Published: July 2012

Previous work has shown that parathyroidectomy (PTX) decreases cardiovascular reactivity to noradrenaline in Sprague‐Dawley rats with mineralocorticoid‐induced (D) hypertension.
In order to explain this diminution of cardiovascular reactivity, we studied in vivo the influence of serum calcium levels on the cardiac and vascular response to noradrenaline (500 ng/kg). We used rats with or without parathyroids but fed a standard or a high‐calcium (+Ca) diet that re‐established a serum calcium level of about 100 mg/l. Work was performed in vagotomized, anaesthetized rats after ganglionic blockade with pentolinium and atropine sulphate.
Cardiac output was unchanged in all the experimental groups after 11 weeks of mineralocorticoid treatment. The enhancing effect of noradrenaline was not modified.
Since a serum calcium level of about 100 mg/l was sufficient to re‐establish vascular reactivity to exogenous noradrenaline in the PTX‐D rats, parathyroid hormone was not necessary.
The total and lanthanum‐resistant calcium fractions of the walls of the aorta were reduced in the PTX‐D rats. When serum calcium levels were re‐established at about 100 mg/l, there was no difference between PTX‐D and D rats.
It is postulated that the decreased storage of calcium in vascular smooth muscle cells of PTX‐D rats depresses the vascular effect of noradrenaline.
THE SELECTIVE ANTIMUSCARINIC ACTION OF STERCURONIUM
Authors: LI C.K. , MITCHELSON F. 
Published: July 2012

The antimuscarinic activity of stercuronium, a competitive neuromuscular blocking drug, has been compared in the anaesthetized guinea‐pig, guinea‐pig atria, bladder and ileum, rabbit atria and the sympathetically innervated rabbit ear artery preparation using carbachol (CCh) as agonist.
In the anaesthetized guinea‐pig, stercuronium (0.2 and 2.0 μmol/kg) produced significantly greater inhibition (P < 0.05) of the bradycardia than of the vasodepressor response produced by CCh, the difference being 2 fold at the low dose and 5.8 fold at the higher dose.
In guinea‐pig atria the negative chronotropic response to CCh was inhibited to a similar degree to the negative inotropic response by stercuronium, whereas in bladder and ileum stercuronium was 17 fold less active as an antimuscarinic drug.
The affinity of stercuronium for the prejunctional muscarinic receptor on sympathetic nerve endings in the rabbit ear artery was similar to that for the muscarinic receptor mediating negative inotropic responses to CCh in the rabbit left atrium, and 2.3 fold less than the affinity for the muscarinic receptors in guinea‐pig atria.
A similar trend was observed with gallamine, another neuromuscular blocking drug, when results obtained in the rabbit ear artery preparation were compared to previously reported data. Also, the affinity of gallamine for muscarinic receptors mediating relaxation of the cat anococcygeus muscle was found to be similar to that for prejunctional muscarinic receptors in the rabbit ear artery.
It is suggested that stercuronium and gallamine have a greater affinity for cardiac receptors and the inhibitory muscarinic receptors on sympathetic nerve endings than for muscarinic receptors mediating contraction of bladder and ileum.
FURTHER STUDIES ON OPIATE RECEPTORS THAT MEDIATE ANTI‐NOCICEPTION: TOOTH PULP STIMULATION IN THE DOG
Authors: SKINGLE M. , TYERS M.B. 
Published: July 2012

The antinociceptive activities of morphine, codeine and dextropropoxyphene (μ‐agonists), buprenorphine and Mr 2034 [(‐)5,9‐dimethyl‐2‐(tetrahydrofurfuryl)‐2′‐hydroxy‐6,7‐benzomorphan](k‐agonists) have been determined against nociceptive responses to electrical stimulation of the tooth pulp in the conscious dog.
Dose‐dependent increases in nociceptive thresholds were obtained for all of the analgesic drugs tested at doses within their antinociceptive range as determined in nociceptive pressure and chemical tests in rodents.
KINETICS OF MORPHINE‐SENSITIVE [3H]‐ACETYLCHOLINE RELEASE FROM THE GUINEA‐PIG MYENTERIC PLEXUS
Authors: DOWN JAMES A. , SZERB JOHN C. 
Published: July 2012

Longitudinal muscle‐myenteric plexus preparations from the guinea‐pig ileum were superfused at a constant rate while isotonic contractions were monitored.
The preparations were superfused with [3H]‐choline while stimulated supramaximally at 0.1 Hz followed by washout in the presence of hemicholinium‐3. The evoked release of the label due to a second 0.1 Hz stimulation in the absence of an anticholinesterase was measured.
Evoked efflux of the label was initially fast followed by a slower phase.
Morphine reduced the size of the pool and the rate of the initial fast efflux and the size of the pool but not the rate of the slow efflux evoked by supramaximal stimulation.
Submaximal stimulation reduced only the size of the pools from which the fast and slow efflux originated.
Naloxone reversed the depression of contractions and evoked release produced by morphine.
Results suggest that 0.1 Hz stimulation releases [3H]‐acetylcholine simultaneously from two pools. The fast release may originate from spontaneously firing units whose rate of discharge is depressed by morphine, while the slow release originates from neurones which do not fire spontaneously and whose threshold to field stimulation is increased by morphine.
CARDIAC β‐ADRENOCEPTORS DURING NORMAL GROWTH OF MALE AND FEMALE RATS
Authors: BAKER STEPHEN P. , POTTER LINCOLN T. 
Published: July 2012

A binding assay involving (−)‐[3H]dihydroalprenolol (DHA) and KCl‐washed cardiac membranes was used to assess the numbers and affinities of β‐adrenoceptors in hearts from male and female rats varying in age from about 2 weeks to 18 months.
Although female rats grow more slowly and attain lower adult weights than male rats, heart weights increased in approximate proportion to body weight with little sex difference.
As heart weight increased about three fold, β‐receptors increased three fold. Since the number of myocardial cells is believed to be nearly constant during postnatal growth, the numbers of receptors/cell presumably increases similarly.
As heart weight increased, the number of β‐receptors per g of tissue decreased according to the equation: total pmol/g = 4.33 − 1.43 × heart weight, equally in males and females.
Dissociation constants for DHA (2 to 4 nm) remained the same, and equal, in male and female rats during their growth.
An excellent correlation was found between the decline in β‐receptors/g tissue during growth and the decline in the area of the external sarcolemma/g tissue. The data suggest that the number of receptors per unit area remains constant during growth, and thus that cell surface area is a major factor determining normal numbers of receptors per cardiocyte.
THE STIMULATORY EFFECTS OF NEUROTENSIN AND RELATED PEPTIDES IN RAT STOMACH STRIPS AND GUINEA‐PIG ATRIA
Authors: QUIRION R. , REGOLI D. , RIOUX F. , ST‐PIERRE S. 
Published: July 2012

The stimulatory effects of neurotensin (NT) and several NT fragments were evaluated in two pharmacological preparations: rat stomach strips and isolated spontaneously beating atria of guinea‐pigs.
In rat stomach strips, NT elicited a dose‐dependent contractile effect in concentrations varying between 1.3 × 10−9 and 5.4 × 10−7 M.
The contractile effect of NT (1.3 and 5.4 × 10−8 m) in this tissue was not modified by atropine (3.4 × 10−7 m), methysergide (2.0 × 10−6 m), a mixture of cimetidine (8.0 × 10−6 m) and diphenhydramine (7.8 × 10−6 m), indomethacin (1.4 × 10−5 m), 8‐Leu‐angiotensin II (1.0 × 10−6 m), glucagon (2.0 × 10−6 m) or somatostatin (3.0 × 10−7 m).
Rat stomach strips desensitized by bradykinin (6.1 × 10−6 m) or substance P (7.4 × 10−6 m) maintained their sensitivities to NT (1.3 and 5.4 × 10−8 m).
In guinea‐pig atria, NT produced a dose‐dependent positive inotropic action in concentrations varying between 5.4 × 10−10 and 2.7 × 10−7 m.
The inotropic effect of NT (2.7 × 10−9 m) was not influenced by methysergide (2.8 × 10−6 m), atropine (3.4 × 10−7 m), practolol (1.5 × 10−5 m), 8‐Leu‐angiotensin II (1.0 × 10−6 m), or indomethacin (1.4 × 10−5 m), but it was reduced by 37% by cimetidine (4.0 × 10−5 and 2.0 × 10−4 m). A combination of cimetidine (4.0 × 10−5 m) and diphenhydramine (3.9 × 10−6 m) did not produce a greater inhibition of NT than cimetidine alone.
Atria desensitized by bradykinin (6.1 × 10−6 m) or glucagon (2.0 × 10−6 m) maintained their sensitivities to NT (2.7 × 10−9 m). Substance P was inactive both as an agonist or antagonist of NT.
These results suggest the existence of specific NT receptors in rat stomach strips and guinea‐pig atria.
The data derived from our structure‐activity study suggest that the minimum structure required for the full stimulation of NT receptors in these two preparations is H‐Arg9‐Pro10‐Tyr11‐Ile12‐Leu13‐OH. The sequence PyroGlu1‐Leu2‐Tyr3‐Glu4‐Asn5‐Lys6‐Pro7‐Arg8‐ and the amino acids Ile12 and Leu13 appear to contribute mainly to the affinity or binding of NT to its receptor. The chemical groups responsible for the full activation (intrinsic activity) of NT receptors seem to be located in the sequence ‐Arg9‐Pro10‐Tyr11.