bluuebunny/crossref_metadata_2025_split huggingface dataset:
POTENTIATION OF NERVE‐INDUCED BLADDER RESPONSES BY TETRAETHYLAMMONIUM IN RELATION TO JUNCTIONAL AND EXTRAJUNCTIONAL MUSCARINIC RECEPTORS
Authors: CARPENTER F.G. 
Published: July 2012

The single stimulus responses elicited in the rat urinary bladder were enhanced up to 3 fold by tetraethylammonium chloride (TEA) in the range 2.5 to 10 mm. Responses elicited by repetitive stimulation at 20 Hz were potentiated much less by 2.5 and 5 mm TEA; 10 mm TEA depressed the responses to less than control levels.
The responses elicited in preparations treated with tetrodotoxin or botulinum toxin during the 20 Hz stimulus trains were one third to one half of control, while single stimulus responses were abolished altogether. After 10 mm TEA the response to the 20 Hz stimulus trains were near control but the single stimulus responses were not restored at all.
The single stimulus response of control and of TEA‐treated bladder preparations were unaffected by atropine (2 × 10−6m) but responses elicited by a 20 Hz stimulus train were reduced more than 40% by atropine. After 5 mm TEA the responses to the 20 Hz stimulus trains that had been partially blocked by atropine were immediately restored to near control levels.
The responses of bladders to carbachol were dose‐dependent in the range 10−6 to 10−5m and were atropine‐sensitive. After 5 mm TEA the means of the responses produced by graded doses of carbachol were less than control; muscarinic receptors that were blocked by TEA are probably also atropine‐sensitive.
It is suggested that muscarinic receptors in the rat urinary bladder may be divided into: (1) junctional receptors that are resistant to atropine and may be indirectly affected by TEA and (2) extrajunctional receptors that are blocked by atropine and may be directly affected by TEA.
ALTERATION OF MEDULLARY RESPIRATORY UNIT DISCHARGE BY IONTOPHORETIC APPLICATION OF PUTATIVE NEUROTRANSMITTERS
Authors: KIRSTEN EDWARD B. , SATAYAVIVAD J. , ST. JOHN WALTER M. , WANG S.C. 
Published: July 2012

Cats with midcollicular decerebration were vagotomized, paralyzed and artificially ventilated. Phrenic nerve activity was recorded as an index of central respiratory rhythm. Medullary respiratory neurones and non‐respiratory cells located in approximation to the ventral respiratory nucleus were tested for their responsiveness to iontophoretically applied γ‐aminobutyric acid (GABA), acetylcholine (ACh) and glutamate.
GABA tended to inhibit, whereas ACh and glutamate excited activity both of respiratory and non‐respiratory units. Some phase‐spanning respiratory unit activities were converted to phasic discharge patterns linked to either inspiration or expiration concomitant with application of low GABA doses. Appropriate applications of GABA also resulted in a complete cessation of the respiratory or non‐respiratory neuronal activities.
While application of ACh or glutamate induced continuous firing in phasic, phase‐spanning respiratory neurones, the periodic discharge patterns of inspiratory or expiratory units was not altered by ACh or, in many instances, by glutamate. Only at high doses of glutamate was the phasic discharge of some inspiratory or expiratory units converted to tonic activity.
These observations suggest that strong inhibitory processes serve to maintain the phasic firing pattern of respiratory units. These data also support the concept that active‐inhibitory phase‐switching mechanisms serve to define respiratory rhythmicity.
THE EFFECTS OF PIPEROXAN ON UPTAKE OF NORADRENALINE AND OVERFLOW OF TRANSMITTER IN THE ISOLATED BLOOD PERFUSED SPLEEN OF THE CAT
Authors: BLAKELEY A.G.H. , SUMMERS R.J. 
Published: July 2012

The competitive α‐adrenoceptor blocking agent, piperoxan, in concentrations up to 2 × 10−4m, produced large dose‐dependent increases in transmitter overflow from the isolated blood perfused spleen of the cat following nerve stimulation at 10 hertz.
At concentrations greater than 2 × 10 −4 m, piperoxan produced a rise in perfusion pressure, a contraction of the splenic capsule, and a marked dose‐dependent decrease in transmitter overflow.
Phenoxybenzamine (10−4m) and desmethylimipramine (3 × 10−5m) produced further increases in transmitter overflow when added after piperoxan.
Piperoxan (5.8 to 6.6 × 10−6m) had no effect on the recovery of 3H in the venous blood following the close arterial infusion or injection of [3H]‐(−)−noradrenaline, indicating that the drug does not inhibit uptake of the amine.
Piperoxan produced dose‐dependent inhibition of responses of the splenic vasculature to close arterial injection of 1 μg of (—)‐noradrenaline but was much less effective at inhibiting responses to nerve stimulation. At 2 × 10 −6m piperoxan produced a considerable reduction of the response to injected noradrenaline but potentiated the response to nerve stimulation.
In isolated strips of cat splenic capsule, piperoxan produced a shift to the right of the dose‐response curve to noradrenaline with no change of the maximum response. There was no evidence of a postsynaptic sensitizing effect of the type observed in the rat vas deferens.
OCCURRENCE OF H,‐ AND H2‐HISTAMINE RECEPTORS IN THE GUINEA‐PIG GALL BLADDER in situ
Authors: IMPICCIATORE M. 
Published: July 2012

Histamine has a dual action on the in situ gall bladder of the guinea‐pig: a spasmogenic and a relaxant effect mediated through Hr and H2‐receptor stimulation respectively.
The contracturant action, mimicked by 2‐(2‐aminoethyl) thiazole (a specific Hx‐receptor agonist), is blocked by mepyramine and the relaxation, mimicked by dimaprit (a specific H2‐receptor agonist), is inhibited by cimetidine.
SOME OBSERVATIONS ON THE DEVELOPMENT OF ADRENERGIC INNERVATION IN RABBIT INTESTINE
Authors: GULATI O.D. , PANCHAL D.I. 
Published: July 2012

Stimulation of periarterial nerves to the ileum of 1 to 12 day old rabbits with supramaximal voltages and frequencies of 1, 2, 5, 10 and 20 Hz with square wave pulses of 2–5 ms duration for 30–40 s produced responses that were initially contractor. In the course of the first week, the responses changed from motor to inhibitory, the change occurring first at the highest rates of stimulation. By the 7th day of life, almost all responses were inhibitory.
The motor responses were potentiated by physostigmine and blocked by hyoscine suggesting that they were mediated by acetylcholine.
In preparations from rabbits older than 3 days, motor responses could be converted to inhibitory ones by prior exposure to noradrenaline (NA, 1 (ig/ml) for 20 min. This procedure also significantly increased the responses which were already inhibitory.
The ability of the ileum to take up NA increased with age. This uptake was blocked by cocaine.
The following explanations are possible: (a) changeover from cholinergic to adrenergic transmission in sympathetic fibres; (b) existence of ‘parasympathetic’ splanchnic nerves or a permanent cholinergic ‘sympathetic’ component of splanchnic nerves and (c) temporal delay in the development of adrenergic nerves (compared with cholinergic nerves) in the intestine.
RECIRCULATION OF PROSTACYCLIN (PGI2) IN THE DOG
Authors: DUSTING G.J. , MONCADA S. , VANE J.R. 
Published: July 2012

The inactivation of prostacyclin (PGI2) in the circulation of anaesthetized dogs has been studied by the blood‐bathed organ bioassay technique.
Spiral strips of bovine coronary and rabbit coeliac or mesenteric artery detected concentrations of PGI2 of 2 to 5 ng/ml. These tissues were insensitive to concentrations at least 200 fold higher of 15‐oxo‐PGI2 and 6‐oxo‐PGFlat.
PGI2 assayed on bovine coronary artery, rabbit coeliac artery or rat stomach strip, had a half life in blood of 3.0 + 0.3 min, indicating non‐enzymatic degradation.
No disappearance could be detected by bovine coronary artery when PGI2 was infused across the lungs (0.1 to 0.5 (ig kg−1 min−1). However, PGI2 was partially inactivated in passage through vascular beds of hindquarters and liver.
Of PGI2 infused into the aorta 35 to 65% escaped inactivation in one complete circulation. Therefore, endogenous PGI2 released from the lungs may function as a circulating hormone.
β‐ADRENOCEPTOR BLOCKING DRUGS AND ISOPRENALINE: CENTRAL EFFECTS ON CARDIOVASCULAR PARAMETERS
Authors: COHEN Y. , LINDENBAUM A. , MIDOL‐MONNET MICHELE , PORQUET D. , WEPIERRE J. 
Published: July 2012

The central hypotensive activity of (+)‐ and (—)‐propranolol (100 μg), pindolol (100 μg) and isoprenaline (1 and 4 μg) injected intracerebroventricularly (i.c.v.) was studied in rats anaesthetized with urethane and chloralose. Blood pressure, cardiac output and heart rate were measured; systolic stroke volume and peripheral vascular resistance were calculated.
(+)‐ and (—)‐Propranolol and pindolol induced a fall of blood pressure but (+)‐propranolol was less active. The heart rate was reduced more by (—)‐propranolol than by (+)‐propranolol or (—)‐pindolol. The decrease of systolic stroke volume was greater for (—)‐propranolol and pindolol than for (+)‐propranolol. Peripheral vascular resistance was reduced to the same level but with different time courses, (—)‐propranolol having a longer effect than (+)‐propranolol and pindolol.
Isoprenaline induced a hypotensive effect, while cardiac output and heart rate increased; the systolic stroke volume remained stable but peripheral vascular resistance was significantly decreased.
These results suggest that different central regulatory centres are involved in the control of cardiac function and peripheral vascular tone.
PHARMACOLOGICAL ASPECTS OF NEUROMUSCULAR TRANSMISSION IN THE ISOLATED DIAPHRAGM OF THE DYSTROPHIC (Rej 129) MOUSE
Authors: HARRIS J.B. , RIBCHESTER R.R. 
Published: July 2012

Some aspects of the pharmacology of neuromuscular transmission have been studied in the isolated diaphragm of the normal and dystrophic mouse.
The effects of (+)‐tubocurarine and atropine on the indirectly elicited twitch responses of the dystrophic diaphragm were indistinguishable from normal.
Intracellular recording techniques revealed no significant differences between the rise time, time to half decay, frequency and amplitude of miniature endplate potentials (m.e.p.ps) recorded in dystrophic muscle fibres, compared to those recorded in normal muscle fibres.
Transmitter null potential, the size of the available store of transmitter, the probability of release of the transmitter, and the characteristics of endplate potentials (e.p.ps) of dystrophic muscle fibres did not differ from normal.
The quantum contents of e.p.ps generated in response to nerve stimulation of 0.1 to 100 Hz were consistently larger in dystrophic muscle fibres than in normal muscle fibres, but the differences were not statistically significant under the conditions of the experiment.
VENTILATORY DEPRESSION IN NAIVE AND TOLERANT RATS IN RELATION TO PLASMA MORPHINE CONCENTRATION
Authors: BOWEN S.R. , CARPENTER F.G. , SOWELL J.G. 
Published: July 2012

The disappearance of morphine from specially formulated pellets containing 75 mg morphine base was measured for 10 days after they were implanted into adult rats; the morphine content decreased at a rate of 5 mg pellet daily.
From the 2nd to the 6th day of implantation the plasma morphine concentration increased but by the 10th day had declined to only one half the concentration found on day 6.
Six and 24 h after the pellets were removed from 6 day implanted animals the plasma concentration of morphine amounted to only one quarter to one sixth of the amount in the plasma, respectively, of animals with pellets intact.
The pulmonary minute volume of naive and implanted rats was depressed by morphine in proportion to the plasma morphine concentration. Less depression was produced by intravenous morphine in the implanted rats than in the naive animals; the greater morphine tolerance displayed by the implanted animals could be shown by the third day of implantation and appeared to be maintained to the 10th day.
The pulmonary minute volume of implanted rats on the 6th day was much less than the pulmonary minute volume of naive rats. Six and 24 h after the pellets were removed the pulmonary minute volume increased as the plasma morphine concentration decreased.
The effects on the pulmonary minute volume produced by the slow release of morphine from the implanted pellets was not changed by the development of tolerance while the effects of morphine produced by rapid injection were diminished by the development of tolerance; the different effects of morphine are accordingly linked to the mode of administration.
We conclude that the action of morphine on the pulmonary minute volume in tolerant rats following rapid injection is fundamentally different from its action following its slow release from implanted pellets, possibly due to differences in access to an undefined neuronal site.
SHAPE CHANGE OF BLOOD PLATELETS—A MODEL FOR CEREBRAL 5‐HYDROXYTRYPTAMINE RECEPTORS?
Authors: GRAF M. , PLETSCHER A. 
Published: July 2012

In blood platelets of rabbits isolated by a stractan gradient and incubated in a protein‐poor medium, tryptamine, 5‐hydroxytryptamine (5‐HT) and derivatives, quipazine and mescaline caused a shape change. This shape change was inhibited by low concentrations of methysergide.
The most potent antagonists of the 5‐HT‐induced shape change included ergoline derivatives and neuroleptic drugs, which showed high stereoselectivity.
(‐f)‐Lysergic acid diethylamide ((+)‐LSD), psilocine and some N',N′‐dimethylated tryptamines acted as mixed agonist‐antagonists.
The compounds found to be agonists or mixed agonist‐antagonists on platelets have previously been shown to act also as 5‐HT agonists in the central nervous system (CNS).
With regard to 5‐HT antagonists, the 5‐HT receptors of platelets reacted differently from those described earlier in brain areas with dense 5‐hydroxytryptaminergic innervation, but showed similarities to 5‐HT receptors investigated previously in spinal cord, cerebral cortex and possibly reticular formation.
It is concluded that platelets may be considered with caution as models for some, but not for all, 5‐HT receptors in the CNS.
THE CHARACTERISTICS OF [3H]‐CLONIDINE BINDING TO ANα‐ADRENOCEPTOR IN MEMBRANES FROM GUINEA‐PIG KIDNEY
Authors: JARROTT B. , LOUIS W.J. , SUMMERS R.J. 
Published: July 2012

[3H]‐clonidine binds to membranes prepared from guinea‐pig kidney.
At 25°C the binding is rapid and saturable.
Scatchard analysis of the binding data showed that the Kd for [3H]‐clonidine binding in kidney membranes is 8.54 nM and the density of binding sites 12.5 pmol/g wet wt. tissue.
Hill plots of the binding data showed that there were no cooperative site interactions associated with binding.
[3H]‐clonidine binding could be displaced by drugs, the most potent being drugs with a high affinity for the α‐adrenoceptor. The neuroleptic drugs (+)‐butaclamol, ds‐clopenthixol and ds‐flupen‐thixol at high concentration also displaced [3H]‐clonidine binding.
Drugs acting as agonists or antagonists of β‐adrenoceptors, histamine receptors, acetylcholine receptors as well as prostaglandins E1 E2, Flα and F2α, angiotensin II, arginine vasopressin, naloxone, nalorphine and pargyline had little effect on binding.
It is likely that the binding site labelled by [3H]‐clonidine in guinea‐pig kidney membranes is an α‐adrenoceptor similar in some pharmacological aspects to an a2‐adrenoceptor.
ASSESSMENT OF THE EFFECTS OF VASOACTIVE INTESTINAL PEPTIDE (VIP) ON BLOOD FLOW THROUGH AND SALIVATION OF THE DOG SALIVARY GLAND IN COMPARISON WITH THOSE OF SECRETIN, GLUCAGON AND ACETYLCHOLINE
Authors: SHIMIZU T. , TAIRA N. 
Published: July 2012

The vascular bed of the submandibular gland in situ was perfused with blood through the glandular artery at a constant pressure in anaesthetized dogs. All drugs were administered intra‐arterially.
Vasoactive intestinal peptide (VIP), secretin and acetylcholine produced a dose‐dependent increase in blood flow through the artery (vasodilatation) but glucagon was almost ineffective.
Dose‐blood flow response curves for VIP and secretin were parallel, and VIP was about 100 times as potent as secretin on a molar basis. Dose‐blood flow response curves for acetylcholine were flatter than those for VIP and secretin. Acetylcholine was approximately as potent as secretin on a molar basis.
No tachyphylaxis developed to the vasodilator action of VIP.
The vasodilator responses to VIP and to electrical stimulation of the chordolingual nerve were scarcely modified by (—)‐hyoscyamine in doses that fully antagonized the vasodilator response to acetylcholine.
VIP, secretin and glucagon were ineffective in eliciting salivary secretion.
The possibility that VIP is released from parasympathetic vasodilator nerves and mediates the atropine‐resistant vasodilatation in the dog submandibular gland is discussed.
OUABAIN RECEPTOR BINDING OF HYDROXYPROGESTERONE DERIVATIVES
Authors: CHOW EDWIN , KIM RYUNG‐SOON SONG , LABELLA FRANK S. , QUEEN GARY 
Published: July 2012

A specific and sensitive radioreceptor assay has been devised which is based on high affinity, saturable binding of 9 nm [3H]‐ouabain to the total particulate fraction isolated from dog heart. Ouabain and other cardiac glycosides, including the aglycones, were about equipotent in their ability to displace [3H]‐ouabain from its receptor, the IC50s ranging from 10 to 30 nm.
The only other substances found to compete significantly in the assay were derivatives of hydroxy‐progesterone having a 17α‐acetate substituent: chlormadinone acetate, megestrol acetate, cyproterone acetate and medroxyprogesterone acetate, with IC50s of 2, 7.4, 9 and 21 μm, respectively. Prednisolone‐3,20‐bisguanyl‐hydrazone, reported to have inotropic activity, gave an IC50 of 6.4 μm. Cyproterone‐17α‐OH was less active (IC50 90 μm) than cyproterone‐17α‐acetate.
A large number of peptide and protein hormones, steroid hormones and their metabolites, amines, and drugs were inactive.
THE ORAL ACTIVITY OF Δ′‐TETRAHYDROCANNABINOL AND ITS DEPENDENCE ON PROSTAGLANDIN E2
Authors: FAIRBAIRN J.W. , PICKENS JOAN T. 
Published: July 2012

Δ′‐trans‐Tetrahydrocannabinol (THC) is more active orally in mice than previously thought, as cataleptic responses occur at doses from 0.06mg/kg upwards, with peak activity at 2 to 4 h after dosing. These doses and peaks correspond well with the effects in man.
Comparison with chlorpromazine in mice shows that chlorpromazine and THC are equipotent as cataleptics during the first 2 h after dosing; thereafter the THC activity increases to a peak when it is 5.67 times as active as chlorpromazine.
The cataleptic effect of THC is abolished by aspirin, indomethacin, diflunisal and phenylbutazone which inhibit the biosynthesis of prostaglandins and is restored by exogenous prostaglandin E2 (PGE2) but not PGE1 and PGF2. This suggests that the effect of THC depends upon the presence of PGE2.
In contrast, the cataleptic effect of chlorpromazine is not affected by pretreatment with aspirin.
THC is very much less active intraperitoneally than orally; our results suggest this is not due to poor absorption or extraction into fat depots.
Cannabidiol has no cataleptic effect.
INHIBITION OF GUINEA‐PIG LYMPHOCYTE ACTIVATION BY HISTAMINE AND HISTAMINE ANALOGUES
Authors: BEETS J.L. , DALE M. MAUREEN 
Published: July 2012

The incorporation of [3H]‐thymidine into guinea‐pig lymphocytes stimulated by a plant lectin (concanavalin A), soluble antigen (tuberculin (P.P.D.)) and syngeneic hepatoma cells, was partially inhibited (50%) by histamine in vitro.
The effect of histamine on both mitogen and antigen dose‐response curves suggests a non‐competitive, probably physiological antagonism.
The inhibitory dose range of histamine lay between 10 nm and 30 μm with an ID50 of approximately 400 nm.
The potency order for histamine analogues for the inhibition of lymphocyte activation was histamine ≥ 4‐methylhistamine > 2‐methylhistamine > 3‐methylhistamine. This is in accord with the mediation of the response through an H2‐receptor.
H2‐receptor antagonists reversed the inhibitory effect of histamine in a dose‐related manner, but both metiamide and burimamide, in high concentrations, augmented lymphocyte activation in their own right. This precluded the determination of affinity constants and made it impossible to state with certainty that the inhibition of lymphocyte activation by histamine was mediated by an H2‐receptor.
ACTIONS OF PROSTAGLANDIN PRECURSORS AND OTHER UNSATURATED FATTY ACIDS ON CONDUCTION TIME AND REFRACTORY PERIOD IN THE CAT HEART in situ
Authors: BAYER B.‐L. , FÖRSTER W. 
Published: July 2012

The effect of arachidonic, dihomo‐γ‐linolenic, linoleic, α‐linolenic and oleic acid, given by intravenous infusion, on conduction time and functional refractory period have been studied in the cat heart in situ.
The prostaglandin precursors, arachidonic acid and dihomo‐γ‐linolenic acid, prolonged the conduction time and the functional refractory period. Linoleic acid was also effective but to a lesser degree. α‐Linolenic acid and oleic acid showed no or only a weak effect in this respect.
Pretreatment with indomethacin diminished or abolished the actions of the three effective fatty acids but not those of prostaglandin E2.
The results suggest that the effects of prostaglandin precursors on conduction time and refractory period are responsible for their antiarrhythmic effectiveness and that these effects are attributable to their endogenous conversion into prostaglandins.
THE EFFECTS OF H1‐ AND H2‐RECEPTOR AGONISTS AND ANTAGONISTS ON TOTAL LUNG RESISTANCE, DYNAMIC LUNG COMPLIANCE AND IRRITANT RECEPTOR DISCHARGE IN THE ANAESTHETIZED DOG
Authors: DIXON M. , JACKSON D.M. , RICHARDS I.M. 
Published: July 2012

The effects of histamine and 4 methylhistamine (i.v.) alone, and in the presence of chlorpheniramine or cimetidine, on total lung resistance (RL), dynamic lung compliance (Cdyn) and irritant receptor activity have been studied in dogs anaesthetized with chloralose.
Histamine produced dose‐related increases in RL and irritant receptor activity with associated falls in Cdyn which were blocked by chlorpheniramine but unaffected by cimetidine.
4 Methylhistamine produced small insignificant changes in R1 and Cdyn and small significant increases in irritant receptor activity which were reduced with chlorpheniramine but unaffected by cimetidine.
The results suggest that histamine increases irritant receptor activity, either directly or indirectly, via H1‐receptors.
DECREASED BINDING OF DRUGS AND DYES TO PLASMA PROTEINS FROM RATS WITH ACUTE RENAL FAILURE: EFFECTS OF URETER LIGATION AND INTRAMUSCULAR INJECTION OF GLYCEROL
Authors: BOWMER C.J. , LINDUP W.E. 
Published: July 2012

The decreased binding of drugs and dyes to plasma proteins from male and female rats with acute renal failure has been investigated using equilibrium dialysis at 37°C.
Acute renal failure induced by bilateral ligation of the ureters produced a greater than threefold increase in the unbound fraction of o‐methyl red relative to normal rat plasma. Unbound dye concentration in plasma from sham‐operated control rats was also significantly increased but to a lesser extent.
Glycerol‐induced acute renal failure produced a significant increase in the unbound fractions of o‐methyl red, methyl orange, bromocresol green (BCG), 2‐(4′‐hydroxybenzeneazo) benzoic acid (HABA), phenytoin and salicylic acid. A marginally significant increase in unbound warfarin concentration was observed.
Glycerol‐induced renal failure had no effect on total plasma protein concentration and experiments with o‐methyl red and salicylic acid indicated that a direct effect of glycerol was not responsible for the diminution of binding.
Glycerol‐induced acute renal failure, which produced decreases in drug and dye binding similar to those reported for human uraemic plasma, provides a convenient non‐surgical animal model for the investigation of this phenomenon.