bluuebunny/crossref_metadata_2025 huggingface dataset:
Renin‐like activity of the rat submaxillary gland: characterization and the effect of several drugs and stimuli
Authors: GUTMAN Y. , LEVY M. , SHORR J.
Published: July 2012

Renin‐like activity was found in rat submaxillary glands.

This activity was destroyed by boiling, was non‐dialyzable and showed an optimum at approximately 50° C.

Renin‐like activity in the submaxillary gland was not diminished 24 h after nephrectomy but was considerably reduced after ligature of the submaxillary duct.

Renin‐like activity in the submaxillary gland was reduced following food‐deprivation, water‐deprivation or hypovolemia.

Renin‐like activity in the rat submaxillary gland was increased after isoproterenol administration but not following pilocarpine.

Renin‐like activity in the rat submaxillary gland was increased considerably by administration of NaCl or KCl, as well as following adrenalectomy.

Chlorothiazide and ouabain increased submaxillary renin‐like activity but diazoxide did not affect this activity.
The effects of diphenylhydantoin and potassium on the biological activity of ouabain in the guinea‐pig heart
Authors: BASKIN S. I. , DUTTA S. , MARKS B. H.
Published: July 2012

Diphenylhydantoin (DPH) and potassium significantly prevent ouabain intoxication without preventing the inotropic effects of ouabain in the guinea‐pig isolated heart.

The antiarrhythmic effect of DPH and K on ouabain‐induced toxicity appears to be related to their ability to reduce ouabain accumulation by the myocardium and thereby prevent the intracellular Na and K changes which lead to the arrhythmic state.
Preferential release of newly synthesized 3H‐acetylcholine from rat cerebral cortex slices in vitro
Authors: MOLENAAR P. C. , NICKOLSON V. J. , POLAK R. L.
Published: July 2012

Slices of rat cerebral cortex after treatment with the irreversible cholinesterase inhibitor soman, were incubated for 5 min in a Krebs‐Henseleit solution containing 25 mm KCl and 3H‐choline. Subsequently incubation was continued in a medium containing non‐radioactive choline and this medium was replaced at 5 min intervals. The amounts of labelled and total acetylcholine (ACh) released into the medium and extracted from the slices were determined at intervals.

After the initial 5 min contact with 3H‐choline, 44% of the newly synthesized ACh contained a choline moiety originating from the choline in the medium. During the initial 5 min and the subsequent incubation part of the labelled ACh was released. While the rate of total ACh release remained constant, that of the release of labelled ACh was highest in the 5 min period following the initial incubation with 3H‐choline and then declined exponentially.

The ratio of labelled ACh/total ACh in the ACh released during the initial 5 min incubation with 3H‐choline and during the subsequent 5 min was about three times as high as that in the ACh extracted from the slices at the end of these incubation periods.

The ratio of labelled ACh/total ACh in superficial layers of the slices was not higher than that in the total slices.

The rates of release of labelled and unlabelled ACh decreased when calcium was omitted from the incubation medium and were restored when the calcium was added. This suggests that both labelled and unlabelled ACh were released from nerve endings. The efflux of 3H‐choline was not calcium dependent.

It is concluded that labelled ACh newly synthesized from externally applied 3H‐choline does not exchange immediately with all other ACh in the tissue and has a greater chance of being released than unlabelled ACh.
Some pharmacological effects of the nematocide, morantel
Authors: BAMGBOSE S. O. A. , MARQUIS V. O. , SALAKO L. A.
Published: July 2012

In isolated nerve‐muscle preparations as well as in nerve‐muscle preparations in intact anaesthetized animals, morantel exhibited neuromuscular blocking properties similar to those of depolarizing blockers. The drug also caused spastic paralysis of 3 day‐old chicks and contracture of the isolated toad rectus abdominis muscle.

Morantel caused contraction of the guinea‐pig and rabbit isolated small intestine. This effect was antagonized by atropine and hexamethonium.

Morantel caused an increase in the blood pressure of the anaesthetized rat and cat and contraction of the nictitating membrane of the anaesthetized cat. These effects were antagonized by hexamethonium.

It was concluded that morantel (like the related compound pyrantel) has acetylcholine‐like action and that its structure is consistent with such action.
Action of several β‐adrenoceptor blocking drugs in the pregnant sheep and foetus
Authors: TRUELOVE J. F. , PETTEN G. R. Van , WILLES R. F.
Published: July 2012

The effect of several β‐adrenoceptor blocking drugs on the pregnant ewe and foetus were studied. Bunolol, butidrine, oxprenolol, propranolol and USVP65‐24 all crossed the ovine placenta and produced a β‐adrenoceptor blockade in the ovine foetus. AH3474, AY21011 and sotalol did not cross the ovine placenta as assessed by the absence of a β‐blockade in the foetus when these compounds were administered to the pregnant ewe.

Of the β‐blocking compounds tested, only propranolol and oxprenolol produced a prolonged blockade in the foetus. The β‐blockade with propranolol was of 3 h duration in the ewe and 10 h duration in the foetus. Oxprenolol produced a β‐blockade of 3 h duration in the ewe and 8 h in the foetus.

The β‐blocking drugs which did cross the ovine placenta were more soluble in organic solvents (ether, chloroform, corn oil and olive oil) than those which did not cross the ovine placenta.
Interaction between tyramine and iproniazid on guinea‐pig atria
Authors: DE JALÓN P. D. GARCIA , MARTINEZ‐SIERRA R. , VELASCO A.
Published: July 2012

The inhibition of monoamine oxidase (MAO) by iproniazid may be antagonized by large doses of tyramine as shown by the restoration, or otherwise, of inotropic responses to tyramine in isolated atria from guinea‐pigs that had been treated with reserpine.
Effects of cocaine or denervation on responses of isolated strips of cat spleen to (‐)‐noradrenaline and (‐)‐isoprenaline
Authors: GRANATA A. R. , LANGER S. Z.
Published: July 2012

A study has been made of the effects of cocaine and sympathetic denervation on responses of the cat spleen to (–)‐noradrenaline and (–)‐isoprenaline.

Responses of isolated strips of spleen capsule to (–)‐noradrenaline or to (–)‐isoprenaline were not affected by reserpine‐pretreatment.

In adult cats, cocaine (1 and 10 μg/ml) or denervation produced a shift to the left of dose‐response curves to (–)‐noradrenaline, whereas they failed to modify dose‐response curves to (–)‐isoprenaline.

There was an increase in the maximum development of tension to (–)‐noradrenaline after denervation or in the presence of cocaine (10 μg/ml). These procedures did not increase the maximal responses to (–)‐isoprenaline.

Cocaine (10 μg/ml) did not affect dose‐response curves to (–)‐noradrenaline or (–)‐isoprenaline in the denervated spleen.

In the kitten spleen, cocaine (1 and 10 μg/ml) produced a shift to the left of dose‐response curves to (–)‐noradrenaline both in untreated and in reserpine‐pretreated tissues.

There was a small shift to the left in dose‐response curves to (–)‐isoprenaline in the presence of cocaine in the untreated but not in the reserpine‐pretreated kitten spleen.

It is concluded that the potentiation of responses to (–)‐noradrenaline in the cat's spleen is due to a prejunctional effect of cocaine.
The detection of differential β‐adrenoceptor blockade in the cat
Authors: PARKES M. W.
Published: July 2012

Tachycardia and bronchodilatation were produced by intravenous dimethyl‐phenylpiperazinium iodide (DMPP) in the spinal or pithed cat. Responses other than those involving β‐adrenoceptors were minimized by appropriate blocking agents.

With intact adrenals, both the tachycardia and bronchodilatation with 10 μg/kg DMPP were equal to those with 1 μg/kg adrenaline.

After adrenalectomy, tachycardia with 100 μg/kg DMPP was equal to that with 1·5 μg/kg adrenaline, but the bronchodilatation was equal to that with only 0·3 μg/kg. This difference may reflect the relative activity of the sympathetic supply to the organs.

After adrenalectomy, propranolol was 3 times as effective against bronchodilatation due to DMPP as against tachycardia. Practolol was inactive against bronchodilatation.

With intact adrenals, propranolol reduced both tachycardia and bronchodilatation due to DMPP equally. Propranolol also antagonized equally both effects of adrenaline in the pithed cat after adrenalectomy.

In the spinal cat, propranolol caused bradycardia and bronchoconstriction that persisted after adrenalectomy or pithing. It was reduced by pempidine and guanethidine and is attributed to spontaneous adrenergic neuronal activity.

The Appendix describes a device for cycle‐by‐cycle spirometry and correction for zero drift of a micromanometer, used in this study for the continuous recording of bronchial resistance.
Central noradrenergic neurones and the cardiovascular actions of clonidine in the rabbit
Authors: DOLLERY C. T. , REID J. L.
Published: July 2012

Clonidine (1 μg/kg), given by intracisternal injection to anaesthetized rabbits, lowered mean arterial blood pressure by 33 mmHg and heart rate by 32 beats/min.

In animals pre‐treated with 6‐hydroxydopamine (6‐OHD 500 μg/kg intracisternally) 7–10 days before, intracisternal clonidine (1 μg/kg) reduced mean arterial blood pressure by only 2·5 mmHg and heart rate by 4 beats/minute.

The hypotensive action of intravenous clonidine was reduced to 49% of control by pre‐treatment with intracisternal 6‐OHD. In unanaesthetized normal animals intravenous clonidine (30 μg/kg) lowered mean arterial blood pressure by 19·3 mmHg, while after 6‐OHD it fell only 94 mmHg.

These studies suggest that the central hypotensive effect of clonidine is dependent on the integrity of central monoaminergic neurones.
Effects of histamine on hepatic volume (outflow block) in anaesthetized dogs
Authors: GREENWAY C. V. , OSHIRO G.
Published: July 2012

Hepatic volume was recorded by plethysmography in dogs anaesthetized with sodium pentobarbitone. Histamine infusions into the hepatic artery or portal vein increased hepatic volume while hepatic sympathetic nerve stimulation decreased the volume. Simultaneous nerve stimulation and histamine infusion decreased hepatic volume.

The hepatic volume responses to histamine and nerve stimulation could not be explained on the basis of differences in the responses of the larger hepatic veins and the possibility of a histamine‐sensitive sphincter at the junction of the hepatic vein with the inferior vena cava was excluded. Differences in the responses of the hepatic arterial bed contributed to but did not explain the different hepatic volume responses.

It is suggested that histamine produced an intense and specific constriction of the sublobular veins with passive distension of post‐sinusoidal venules, sinusoids and portal venules while hepatic nerve stimulation produced a uniform and generalized constriction of both pre‐ and post‐sinusoidal vessels.

Intravenous infusions of histamine produced a marked hypotension but small variable effects on hepatic volume. It is concluded that hepatic pooling is not the cause of the hypotension produced by intravenous histamine and that significant hepatic pooling will only be produced by mechanisms which release endogenous histamine within the liver.
Changes in plasma levels of vasopressin and renin in response to haemorrhage in dogs
Authors: COUSINEAU D. , GAGNON D. J. , SIROIS P.
Published: July 2012

The rabbit rectum superfused with blood or Krebs solution was used to assay vasopressin in circulating blood and in plasma extracts respectively.

Vasopressin was released by a rapid fall in diastolic pressure of as little as 5 mmHg, and the amount of vasopressin released was proportional to the magnitude of the fall in diastolic pressure in the range studied. These results would indicate that vasopressin release follows the magnitude of the fall in diastolic pressure more closely than the actual decrease in blood volume in haemorrhagic hypotension.

It was shown that the time required to induce an increase in circulating vasopressin is inversely proportional to the severity of the fall in diastolic pressure; this suggested that the stimulation of neurosecretory reflex arc varies with the intensity of the stimulus.

The slight changes in plasma renin activity as well as the pattern of renin release suggested the unlikeliness of the influence of renin upon vasopressin secretion under these circumstances. On the contrary, the results suggested that the secretion of large amounts of vasopressin tended to inhibit renin release.
Structure‐activity relations for the inhibition of catecholamine uptake into synaptosomes from noradrenaline and dopaminergic neurones in rat brain homogenates
Authors: HORN A. S.
Published: July 2012

The effects of various phenylethylamine analogues on the inhibition of 3H‐noradrenaline and 3H‐dopamine uptake into homogenates of rat hypothalamus and corpus striatum respectively, were examined.

Phenolic hydroxyl groups and α‐methylation of the side chain were both found to enhance the affinity for the neuronal uptake sites.

Methoxylation, β‐hydroxylation and N‐methylation were all found to reduce the ability of a compound to inhibit catecholamine transport.

The noradrenaline and dopamine transport systems responded in a quantitatively different manner to the various phenylethylamine analogues. It was found that, in general, the noradrenaline uptake process was more sensitive to structural changes, both positive and negative, than the dopamine system.
An anti‐curare effect of hexamethonium at the mammalian neuromuscular junction
Authors: FERRY C. B. , MARSHALL A. R.
Published: July 2012

Experiments were performed on the isolated phrenic nerve and diaphragm preparation of the rat.

In preparations partly blocked with (+)‐tubocurarine, the twitch amplitude increased after hexamethonium. This enhancement was not seen in preparations partly blocked with Mg++ or with gallamine. High concentrations of hexamethonium produced failure of contraction.

Extracellular endplate potentials were recorded from blocked preparations. The administration of hexamethonium resulted in an increased amplitude of these potentials only in curarized muscle.

Hexamethonium had no anticholinesterase activity nor did it depolarize muscle cells or increase the quantal release of transmitter.

It is concluded that hexamethonium exerts a specific anti‐curare action. Experiments on the recovery of the twitch after washing out antagonists indicate that this process is limited by diffusion. The difference in rates of diffusion of hexamethonium and (+)‐tubocurarine does not account for their interaction. The basis of the anti‐curare action of hexamethonium is discussed.
Effects of angiotensin, catecholamines and cyclic AMP on calcium storage in aortic microsomes
Authors: BAUDOUIN‐LEGROS M. , MEYER P.
Published: July 2012

The binding of calcium observed in microsomal membranes derived from the intimal‐medial layer of rabbit aorta was specifically increased by the magnesium salt of adenosine triphosphate (Mg‐ATP). This calcium uptake was inhibited by potassium and sodium.

Angiotensin II, both in the presence and in the absence of Mg‐ATP, reduced the binding of calcium and increased the release of membrane‐incorporated calcium. These effects were dose‐dependent. Analogues of angiotensin II devoid of intrinsic activity, failed to alter the release of calcium.

Dibutyryl‐cyclic AMP increased the binding of calcium and reduced the rate of its release. The maximal effect was observed at the concentration of 10−5m.

(—)‐Noradrenaline reduced the binding of calcium; this effect was inhibited by phenoxybenzamine. Conversely, adrenaline like cyclic AMP, increased the calcium binding; the effect of adrenaline was suppressed by a β‐adrenoceptor blocking agent.

These observations demonstrate the existence of membranes in rabbit aorta capable of storing calcium. Excitatory drugs seem to affect directly and specifically the binding and release of calcium in these membranes.
Inhibition by γ‐hydroxybutyrate of chlorpromazine‐induced increase in homovanillic acid
Authors: ROTH R H.
Published: July 2012

γ‐Hydroxybutyrate and its lactone precursor, γ‐butyrolactone, when administered in anaesthetic doses block the increase in the cerebral concentration of homovanillic acid normally observed after administration of chlorpromazine or haloperidol.

Other hypnotics such as glutethimide, urethane, chloralose, chloral hydrate and thiopentone do not have this ability even when administered in anaesthetic doses.

The ability of γ‐hydroxybutyrate to block the neuroleptic‐induced increase in cerebral homovanillic acid is not due to a reduction in body temperature since a similar effect is observed in rats treated under conditions (32° C) in which body temperature remains normal.

Possible mechanisms for this action of γ‐hydroxybutyrate are discussed.
On the pharmacology of the γ‐aminobutyric acid receptors on the cuneo‐thalamic relay cells of the cat
Authors: KELLY J. S. , RENAUD L. P.
Published: July 2012

γ‐Aminobutyric acid (GABA) and glycine applied by iontophoresis were equipotent depressants of cuneo‐thalamic relay neurones isolated from the middle third of the cuneate nucleus of cats either decerebrated or anaesthetized with sodium pentobarbitone.

Glycine 13±2 nA and GABA 20±2 nA were equipotent depressors of hair cells (n = 22) and, bicuculline applied by iontophoresis caused a parallel shift to the right of the GABA but not the glycine log‐current response curves. The GABA equipotent dose‐ratio was 2·0 ± 0·2 for bicuculline currents of approximately 144 nA lasting about 11 min in cells excited either transynaptically by peripheral stimulation or postsynaptically by glutamate.

Although a maximal bicuculline current seldom caused a significant shift of the glycine‐log current response curve, many of our records show the onset of the glycine response to be slowed by doses in excess of 84 nA.

Bicuculline also antagonized depressions by β‐guanidinopropionic acid, and δ‐aminovaleric acid which mimicked the action of GABA.

When tested on the same neurone, bicuculline and picrotoxin applied by iontophoresis were equipotent and their effects appear to be additive.

The GABA sensitivity was not modified by repetitive (5 or 6) doses of i.v. bicuculline (0·2 mg/kg).

The antagonism of GABA by bicuculline and picrotoxin appears to be of sufficient specificity to enable the separate roles of GABA and glycine as putative inhibitory transmitters of cuneo‐thalamic relay cells to be determined.
Fate of angiotensin I in the toad Bufo melanostictus
Authors: NG K. K. F.
Published: July 2012

The effects of angiotensin I and II on the blood pressure of pithed toads and the disappearance of angiotensin I and II in the perfused organs of the toad were studied.

Angiotensin I was relatively inactive on the blood pressure of pithed toads; it exhibited less than 3% of the pressor activity of angiotensin II.

Angiotensin I was not converted to angiotensin II during passage through the lungs. There was also no evidence of net conversion during passage through the kidney and hind quarters.

During passage through the lungs, 33–50% of angiotensin I was removed and 25–50% was removed during passage through the hind quarters. No loss of activity was detected when angiotensin II passed through the kidneys.

Angiotensin II passed through the lungs and kidneys without loss but 25–50% disappeared during passage through the hind quarters.

The relatively low pressor activity of angiotensin I together with its lack of conversion to angiotensin II in isolated perfused organs suggest that the converting enzyme is absent in the toad, Bufo melanostictus.
The action of lanthanum and manganese on anaphylactic histamine secretion
Authors: FOREMAN J. C. , MONGAR J. L.
Published: July 2012

In the concentration range 1 nm to 1 μm, lanthanum inhibited the calcium‐dependent component of anaphylactic histamine release, but was without effect on the component which was independent of calcium.

The inhibition of anaphylactic histamine release by lanthanum can be reversed by increasing the calcium ion concentration. The pA2 for the lanthanum‐receptor interaction was found to be 7·6.

Lanthanum also inhibited the activation of anaphylactic histamine release by strontium ions.

The inhibition of anaphylactic histamine release by lanthanum was reversed by eluting the lanthanum from the cells.

In the concentration range 1 to 300 nm, lanthanum had no effect on the histamine release induced by compound 48/80 in a calcium‐free medium, but the effect of calcium on the histamine release by compound 48/80 was antagonized by lanthanum in this range of concentrations.

At concentrations of 10 μm and greater, lanthanum induced a release of histamine in the absence of antigen.

In the concentration range 0·5 to 40 mm, manganese inhibited the calcium‐dependent component of anaphylactic histamine release, but was without effect on the component which is independent of calcium. The inhibition of anaphylactic histamine release by manganese could be reversed by increasing the calcium ion concentration.
Some studies on the influence of chlordiazepoxide on the social interaction of golden hamsters (Mesocricetus auratus)
Authors: POOLE T. B.
Published: July 2012

The effects of a ‘minor’ tranquillizer (chlordiazepoxide) on the social behaviour of male golden hamsters were investigated.

Thirty‐six hamsters were divided into pairs. Each pair was placed in an arena measuring 1 m2; under these conditions the hamsters fought, but once a winner and loser emerged the relationship between the two animals became stabilized. The influence of 50 mg/kg chlordiazepoxide on this stable relationship was investigated and compared with normal behaviour in the arena.

Under the influence of chlordiazepoxide, hamsters showed a significant reduction in ‘aggression’, ‘defensive fighting’ and an increase in ‘investigation’.

When the data for winners and losers were analysed independently, the drug was seen to influence losers more than winners.

It is postulated that the primary influence of chlordiazepoxide is to reduce fear and as a result ‘investigation’ is probably affected indirectly as a behaviour pattern suppressed in an individual showing fear of its opponent.
Influence of reserpine‐induced depletion of noradrenaline on the negative feed‐back mechanism for transmitter release during nerve stimulation
Authors: ENERO MARIA A. , LANGER S. Z.
Published: July 2012

The effects of depletion of endogenous noradrenaline by reserpine‐pre‐treatment on [3H]‐noradrenaline overflow elicited by nerve stimulation were determined in the isolated nerve‐muscle preparation of the cat's nictitating membrane.

Reserpine pretreatment (0·3 mg/kg, s.c., 4 days prior to the experiment) reduced the noradrenaline levels in the smooth muscle of the nictitating membrane to about 10% of the control values while granular retention of [3H]‐noradrenaline had recovered to nearly 40% of the controls.

In the reserpine‐pretreated tissue the fraction release per shock induced by nerve stimulation was 2·2‐fold higher than the value obtained in the untreated tissues. This effect was correlated with the degree of depletion of the noradrenaline stores rather than with the decrease in the response of the effector organ.

Phenoxybenzamine, 2·9 μm reduced the responses to nerve stimulation to the same extent in control and in reserpine‐pretreated tissues. Yet, this concentration of phenoxybenzamine increased by 13‐fold the overflow of the labelled transmitter in the controls and only by 3‐fold in reserpine‐pretreated tissues.

The decrease in effectiveness of phenoxybenzamine in enhancing transmitter overflow after reserpine‐pretreatment appears to be due to the decrease in the total release of the transmitter.

The results obtained support the view that in reserpine‐pretreated tissues decreased transmitter output reduces the activation of the presynaptic α‐adrenoceptors which mediate the negative feed‐back mechanism that regulates transmitter release by nerve stimulation.
The local graft versus host reaction in the rat as a tool for drug mechanism studies
Authors: BECK FRANCES J. , LEVY L. , WHITEHOUSE M. W.
Published: July 2012

A local graft versus host reaction in rats permits the evaluation of drug action on (i) donor (parental) animals and (ii) recipient animals (F1 hybrid) prior to establishing a lymphoid cell graft to detect drugs which might attenuate immunocompetence over a prolonged period (e.g. steroids).

Treatment of the recipient animals after a lymphoid graft readily detects anti‐proliferative agents and may disclose other agents which interfere with the recognition of non‐self by viable graft cells.

Treatment of the cell graft in vitro before innoculation into the recipient animal permits the detection of alkylating agents, wihch effectively deactivate graft cells at non‐toxic concentrations.

Examples are given of how this reaction may be used to evaluate functionally the effects of chemical modification of the cell surfaces of lymphocytes and to detect active metabolites generated from a precursor drug (e.g. cyclophosphamide).

Some novel immunosuppressant drugs are described.
Effects of chlorpromazine on exploration and habituation in the rat
Authors: FILE SANDRA E.
Published: July 2012

The effects of chlorpromazine, 2 and 4 mg/kg, on exploration were investigated under two independent influences—food deprivation and time of day.

Rats had three 3‐minute trials in a hole‐board apparatus; hole‐investigation (head‐dips) and general motor activity were recorded.

On trial 1 chlorpromazine reduced exploration to half the control level, but on trial 3 it had no effect on motor activity or head‐dips.

General activity habituated from trial 1 to 3 in all groups, but some of the drug groups did not show significant habituation of head‐dips, due to the low level of responding on trial 1.
Possible modulating influence of frontal cortex on nigro‐striatal function
Authors: GLICK S. D. , GREENSTEIN S.
Published: July 2012

After administration of (+)‐amphetamine, rats with unilateral ablations of the frontal cortex rotated either ipsilaterally or contralaterally as a function of time after surgery.

At early postoperative intervals (1–7 days), rotation was towards the side of the lesion.

At later times (15–30 days), rotation was towards the intact side.

Repeated testing with amphetamine appeared to slow the time‐course of changes in rotational behaviour.

These results suggest that a dopaminergic nigro‐striatal system is modulated by the frontal cortex and that unilateral removal of the latter produces a denervation supersensitivity of the former.
The effect of N6‐2′‐0 dibutyryl 3′, 5′ cyclic adenosine monophosphate, imidazole and aminophylline on ganglionic transmission in the superior cervical ganglion of the cat
Authors: VARAGIĆ V. M. , ŽUGIĆ M.
Published: July 2012

Dibutyryl cyclic AMP, injected towards the superior cervical ganglion of the cat, produced no consistent responses.

Imidazole, injected towards the ganglion, regularly produced facilitation, both during intermittent and continuous preganglionic stimulation. This effect was dose‐dependent and lasted 2–10 minutes.

Aminophylline, injected towards the ganglion, regularly produced depression of ganglionic transmission, both during intermittent and continuous preganglionic stimulation. This effect was also dose‐dependent and lasted 1–4 minutes. Papaverine produced the same type of response as aminophylline.

Imidazole potentiated the ganglionic response to 1,1‐dimethyl‐4‐phenylpiperazinium iodide (DMPP), while aminophylline depressed it.

The results of the present experiments are consistent with the view that cyclic AMP may have a mediating role in the process of ganglionic transmission.
Prostaglandin E2 and the bovine sphincter pupillae
Authors: POSNER J.
Published: July 2012

The bovine isolated sphincter pupillae incubated in Krebs solution releases a biologically active substance tentatively identified as prostaglandin E2.

The prostaglandin did not appear to be of neural origin or to result merely from tissue degeneration.

The spontaneous release of prostaglandin E2‐like material was related to the tone of the sphincter. Output increased as tone was acquired after setting up the tissue and fell when various procedures were used to reduce the tone.

Low concentrations of E and F‐type prostaglandins produced slow, well‐sustained contractions of the atonic sphincter, prostaglandin E2 being the most potent of those tested. The responses to prostaglandin E2 were antagonized selectively by a prostaglandin antagonist SC‐19220 (a dibenzoxazepine derivative) which in higher concentrations caused dose‐dependent relaxations of the preparation.

Prostaglandins did not appear to modulate transmission from nerve to muscle in the sphincter.

The hypothesis that prostaglandin E2 might be produced to act as a local hormone causing tonic contraction of the sphincter pupillae is discussed.
The effects of E and A prostaglandins on gastric mucosal blood flow and acid secretion in the rat
Authors: MAIN I. H. M. , WHITTLE B. J. R.
Published: July 2012

The effects of prostaglandins E1, E2, A1 and A2 on gastric acid secretion and mucosal blood flow were studied by means of a [14C]‐aniline clearance technique in the anaesthetized rat.

During intravenous administration of these prostaglandins, in doses which almost completely inhibited pentagastrin‐ and histamine‐induced acid secretion, a fall in clearance was observed.

Clearance per unit acid secretion increased during prostaglandin administration, precluding a primary reduction in mucosal blood flow as the mechanism of the antisecretory action.

Prostaglandins increased clearance during basal secretion, indicating a direct vasodilator effect on the gastric mucosa.

The possibility that endogenous prostaglandins contribute to functional vasodilatation in the gastric mucosa and that exogenous prostaglandins may be of clinical value in the treatment of peptic ulcer is discussed.
Some effects of histamine in the depolarized rat uterus
Authors: BLYTH D. I.
Published: July 2012

The relaxant effect of histamine in the isolated rat uterus remained after the preparation was depolarized in a potassium Ringer.

The effect was abolished by the calcium‐chelating agent, ethyleneglycol bis‐aminoethyl ether‐tetraacetic acid (EGTA).

Histamine caused relaxation during calcium‐induced contractures in a depolarized uterus treated with EGTA, but did not produce relaxation during barium‐induced contractures.

While responses of a normally polarized rat uterus to acetylcholine were inhibited by histamine, those of a depolarized uterus were enhanced by histamine. The inhibitory effects of isoprenaline and papaverine on acetylcholine responses were maintained in depolarized preparations.

Both the enhancing effect of histamine on responses to acetylcholine and the relaxation of calcium‐induced contractures were abolished by burimamide, indicating that H2‐receptors mediate the effects of histamine in the depolarized tissue.

A reduction in the rate of exchange of calcium across the depolarized cell membrane was demonstrated with high concentrations of histamine.

The results are consistent with the hypothesis that in the rat uterus, the stimulation of H2‐receptors by histamine is accompanied by a reduction in calcium exchange across the membrane which may result in a decrease in the concentration of free intracellular calcium available to stimulate contraction of the myofilaments. Histamine may act by increasing the binding of calcium within the cell.
A comparison of phenylalkyl‐ and phenoxyalkyltrimethylammonium and triethylammonium salts; their apparent molal volumes at infinite dilution and effects on the frog rectus and guinea‐pig ileum preparations
Authors: BARLOW R. B. , FRANKS FIONA M.
Published: July 2012

The effects of phenoxyalkyltrimethylammonium and triethylammonium bromides on the frog rectus preparation and on the isolated guinea‐pig ileum in the presence of hexamethonium have been compared with those of analogous phenylalkyltrimethylammonium and triethylammonium bromides. Affinity constants have been measured when possible.

The apparent molal volumes at infinite dilution of some of the compounds have been measured from estimates of density made with an Anton Paar precision density meter.

An ether oxygen occupies at infinite dilution in water only about one‐third of the volume occupied by a methylene group.

The replacement of methylene by ether oxygen reduces nicotine‐like activity and affinity for nicotine‐sensitive receptors. The reduction in affinity may be partly due to the decrease in size.

The replacement of methylene by ether oxygen reduces activity and affinity at muscarine‐sensitive receptors but in some compounds there is a bigger reduction in affinity than would be expected simply from the reduction in size.

It is suggested that the affinity of these compounds largely depends on hydrophobic bonding and that effects on water structure in the environment of the receptor may also be involved in the actions of agonists.
Observations on ‘fade’: a complication of the contractile response of smooth muscle to a large dose of an agonist
Authors: FASTIER F. N. , PURVES R. D. , TAYLOR K. M.
Published: July 2012

A study has been made of the time course of contraction of guinea‐pig isolated ileum when suddenly exposed to a high concentration of acetylcholine, carbachol or histamine. With a sufficiently large dose there was a ‘fading’ of the abrupt initial contraction. A sustained contraction followed, provided that the agonist was not washed out of the organ bath.

The fade produced by giving large equipotent doses of acetylcholine and histamine simultaneously was substantially greater than that obtained by giving either agonist alone. It was comparable to that produced by a double dose of acetylcholine or histamine. This result does not support any explanation of fade based on receptor occupancy.

The extent of fade and the level of the sustained contraction were strongly affected by the calcium concentration of the bath fluid: the higher the calcium concentration the less was the fade. It is suggested that fade occurs when there is such intense stimulation of receptors that excitation‐contraction coupling becomes temporarily less efficient due to depletion of calcium from a store.
ANALYSIS OF THE EFFECTS ON BODY TEMPERATURE OF INTRACEREBROVENTRICULAR INJECTION IN ANAESTHETIZED DOGS OF GAMMA‐AMINOBUTYRIC ACID
Authors: DHUMAL V.R. , GULATI O.D. , RAGHUNATH P.R. , SIVARAMAKRISHNA N.
Published: July 2012

The cerebral ventricles of dogs under intravenous pentobarbitone sodium anaesthesia, were perfused with artificial cerebro‐spinal fluid (CSF) at a rate of 0.4–0.5 ml/min from the ventricular to the aqueductal cannulae. The effluent was collected from the aqueductal cannula in 20 min samples. The animals' temperatures were recorded from the rectum.

γ‐Aminobutyric acid (GABA) 0.1–5 mg when injected into the ventricles produced variable temperature effects. Doses of 0.1 and 0.5 mg always produced hyperthermia and 1 and 5 mg doses sometimes produced hyperthermia and sometimes hypothermia.

Intraventricular perfusion with 2‐bromolysergic acid diethylamide (BOL) and hyoscine did not block hyperthermia. Tests on the rat isolated stomach strip or the guinea‐pig isolated superfused ileum for the possible release, respectively, of 5‐hydroxytryptamine or acetylcholine by GABA were negative.

When tested for the presence of prostaglandin E(PGE)‐like substances on the isolated rat stomach strip, both the control effluent and the GABA effluent showed activity, the latter being much more potent. There was a temporal correlation between this effect and hyperthermia. Intraventricularly administered sodium salicylate converted the GABA‐induced hyperthermia to hypothermia and blocked the release of PGE‐like substances.

Hypothermia induced by GABA alone or in the presence of sodium salicylate was associated with the release of noradrenaline into the effluent.

Intraventricular administration of GABA in reserpinized dogs produced hyperthermia and not hypothermia. Similar results were obtained with phentolamine perfusion in normal dogs.

Perfusion with calcium‐free solution blocked both the noradrenaline‐releasing and hypothermic actions of GABA.

It is concluded that hyperthermia associated with intraventricular injections of GABA is due to the release of PGE‐like substance and hypothermia is due to the release of noradrenaline.
THE EFFECTS OF SOME PROSTAGLANDINS ON RESPIRATION IN ANAESTHETIZED CATS
Authors: McQUEEN D.S.
Published: July 2012

Some prostaglandins have been found to be capable of affecting respiration in anaesthetized cats.

Prostaglandins E1, E2, F2α, A1 and A2 all elicited increases in respiratory frequency when administered to cats anaesthetized with either pentobarbitone or α‐chloralose. This effect was abolished by bilateral vagotomy.

Prostaglandins of the E and A series, but not prostaglandin F2α, elicited increases in tidal volume which were accompanied by falls in systemic blood pressure in cats anaesthetized with pentobarbitone. The changes in blood pressure were also obtained in cats anaesthetized with α‐chloralose, but not the tidal volume changes.

It is unlikely that the prostaglandins influenced respiration by direct actions on arterial chemoreceptors or baroreceptors.

Mechanisms by which the prostaglandins may be acting to affect respiration are discussed.
THE EFFECT OF BRETYLIUM ON ENDOGENOUS AND NEWLY‐SYNTHESIZED NORADRENALINE IN THE MICROSOMAL FRACTION OF RAT HEART
Authors: ABBS E.T. , PYCOCK C.J.
Published: July 2012

Bretylium reduced the content of endogenous and newly‐synthesized noradrenaline (NA) and also reduced the specific activity of NA in the microsomal fraction of rat heart. Bretylium also decreased the endogenous NA content of the microsomal subfraction which equilibrated in the 0.7 M sucrose region of a density gradient; it was without effect on the NA content of other subfractions.
HYPOTENSIVE AND VASODILATOR ACTIONS OF SK&F 24260, A NEW DIHYDROPYRIDINE DERIVATIVE
Authors: FIELDEN R. , OWEN D.A.A. , TAYLOR E.M.
Published: July 2012

The blood pressure of conscious normotensive, Goldblatt‐hypertensive and genetic‐hypertensive rats and normotensive dogs was lowered by SK&F 24260 (1,4‐dihydro‐2,6‐dimethyl‐4‐(2‐trifluormethylphenyl)‐3,5‐pyridinedicarboxylic acid diethyl ester).

Tachycardia always accompanied the hypotension. In rats propranolol abolished the tachycardia but in dogs there was only a small reduction in the heart rate response.

In conscious dogs there was an increase in left ventricular output and a marked fall in total peripheral resistance.

SK&F 24260 dilated resistance vessels in rat hindquarters. Dilatation was caused by doses of SK&F 24260 some 50 times smaller than those of hydrallazine.

In preparations of cat skeletal muscle and intestinal vascular beds SK&F 24260 selectively dilated resistance vessels in preference to capacitance vessels and resembled hydrallazine rather than papaverine which has no such selectivity.

Pre‐capillary sphincter vessels were also dilated by SK&F 24260. Changes in fluid equilibrium caused by SK&F 24260 were consistent with selective dilatation of resistance vessels.
FLOW AND COMPOSITION OF SKIN AND MUSCLE LYMPH OF THE HIND LIMB OF THE RABBIT AFTER INJURY
Authors: BACH CATHERINE S. , LEWIS G.P.
Published: July 2012

Collection of skin lymph separately from muscle lymph has enabled us to repeat earlier experiments in which lymph was collected from the whole hind limb to determine whether the changes then observed were the result of changes occurring in the skin or the muscle or both.

After thermal and chemical injury, it appeared that most of the changes were due to leakage of enzymes from the muscle; after freezing, changes occurred in both skin and muscle lymph while ischaemia caused no significant changes in either skin or muscle lymph.

After mild thermal injury it took longer for the enzyme leakage to reach a maximum in muscle lymph than in skin lymph. It seems likely that the changes were buffered by the large tissue space of muscle.

Lactic dehydrogenase (LDH) activity appears to diffuse from muscle into skin since although intramuscular dimethyl sulphoxide (DMSO) causes the release of LDH into skin lymph, subcutaneous DMSO does not.

That proportion of muscle LDH released during injury might represent the unbound or ‘active’ portion since no matter how severe the injury only about 1% of the total muscle LDH was released into the lymph.
RELEASE OF PROSTAGLANDIN FROM THE RABBIT ISOLATED HEART FOLLOWING VAGAL NERVE STIMULATION OR ACETYLCHOLINE INFUSION
Authors: JUNSTAD M. , WENNMALM A.
Published: July 2012

Rabbit hearts were perfused by the Langendorff technique. The lipid fraction in the perfusate from the heart was isolated and analysed for prostaglandins by thin layer chromatography and quantitative assay on the rat isolated stomach strip.

Infusion of acetylcholine at a rate of 8 μg/min significantly increased the outflow of prostaglandins from the heart, from 1.8 to 6.2 ng/minute.

Addition of atropine (1 μg/ml) to the perfusing medium completely abolished not only the mechanical response but also the increase in outflow of prostaglandins caused by infusion of acetylcholine.

Bilateral stimulation of the parasympathetic nerves to the heart at 5 Hz also significantly increased the outflow of prostaglandins from the organ from 5.2 to 8.3 ng/minute.

Both prostaglandin E1 and E2 were isolated from the lipid fraction of the perfusate.

The role of prostaglandins in relation to autonomic neurotransmission in the heart is discussed.
A COMPARISON OF THE EXPERIMENTAL ANTI‐ARRHYTHMIC PROPERTIES OF ACEBUTOLOL: (M & B 17,803), PROPRANOLOL AND PRACTOLOL
Authors: BASIL B. , JORDAN R. , LOVELESS A.H. , MAXWELL D.R.
Published: July 2012

The β‐adrenoceptor blocking agent, acebutolol (M & B 17,803), has been compared with propranolol, practolol, lignocaine and quinidine for its ability to revert or prevent various types of experimental arrhythmias.

By intravenous infusion, acebutolol had one half the potency of propranolol in reverting an established ouabain‐induced ventricular arrhythmia in the anaesthetized dog. Practolol was ineffective in the conditions used.

High oral doses of acebutolol or propranolol significantly increased the arrhythmic dose of ouabain in the conscious rabbit. Similar doses of practolol produced a significant decrease (i.e. potentiation) in the dose of ouabain required to produce arrhythmia. Lignocaine and quinidine showed no or little activity in this test.

Propranolol, acebutolol and practolol were all effective in decreasing the frequency of ectopic beats induced by adrenaline and methylchloroform in the anaesthetized cat. Lignocaine and quinidine were only weakly effective.

Acebutolol and propranolol were equally effective either intravenously or orally in reducing the incidence of ventricular fibrillation produced by chloroform in mice.

It is suggested that the wide spectrum of experimental anti‐arrhythmic activity of acebutolol coupled with its cardioselectivity may make it an interesting compound in the treatment of cardiac arrhythmias in man.
LOWERING OF KININOGEN IN RAT BLOOD BY ADRENALINE AND ITS INHIBITION BY SYMPATHOLYTIC AGENTS, HEPARIN AND ASPIRIN
Authors: CASTANIA A. , ROTHSCHILD A.M.
Published: July 2012

(–)‐Adrenaline lowered the kininogen content and transitorily elevated the fibrinolytic activity of plasma following intravenous injection into the rat. Its effect on kininogen increased when administered by intravenous infusion.

Although less effective, (–)‐noradrenaline had a similar action to adrenaline; (±)‐isoprenaline was inactive and failed to inhibit the effect of adrenaline.

The effect of adrenaline on kininogen could be reproduced in vitro by incubation of whole blood, but not cell‐free plasma, with the catecholamine for 5 min at 37° C.

Propranolol or phenoxybenzamine, as well as heparin or acetylsalicylic acid (aspirin), blocked the reduction of rat blood kininogen by adrenaline in vivo and in vitro.
DISTRIBUTION OF PENTAZOCINE IN BLOOD AND BRAIN OF THE BABOON FOLLOWING INTRAVENOUS INJECTION
Authors: CORONEOS N.J. , KEANEY N.P. , McDOWALL D.G. , PICKERODT V.W.A. , GLYNN J.P. , ROBERTSON A.
Published: July 2012

In the baboon the blood levels of pentazocine between 1 and 60 min after intravenous injection of 0.5 mg/kg were measured by a gas chromatographic technique. From cerebral arteriovenous differences it was shown that the peak of the brain concentration occurred within 15 min and probably within 10 min of intravenous injection. At the time of peak concentration about 10% of the injected dose was in the brain, while the corresponding value at 60 min was 2%.

The concentration of pentazocine in the brain was an order of magnitude greater than the concentration in cerebral venous blood both at 5 min and 60 min after injection. No major brain interregional differences were demonstrated. Cerebrospinal fluid from the cisterna magna did not yield values from which the cerebral concentration of pentazocine could be predicted.
EFFECTS OF Gymnodinium breve TOXIN ON THE SMOOTH MUSCLE PREPARATION OF GUINEA‐PIG ILEUM
Authors: GRUNFELD Y. , SPIEGELSTEIN M.Y.
Published: July 2012

The effects of Gymnodinium breve neurotoxin (GT) on smooth muscles were studied using the guinea‐pig isolated ileum.

The toxin caused strong spasmogenic effects at 1–4 μg/ml, characterized by prolonged tonic contraction with superimposed pronounced pendular movements. Tachyphylaxis was observed upon administration of successive doses.

Atropine blocked the contractile response elicited by GT, whereas mepyramine and hexamethonium failed to do so. These findings tentatively suggested a cholinergic involvement at a post‐ganglionic site of action.

In the presence of tetrodotoxin the effects of GT were abolished, excluding direct action of the toxin on the smooth muscle.

It is concluded that GT exerts its spasmogenic effects through stimulation of the post‐ganglionic cholinergic nerve fibres.
UNCOUPLING ACTIVITY OF THE ANTHELMINTIC OXYCLOZANIDE IN RODENTS
Authors: VEENENDAAL G.H. , DE WAAL M.J.
Published: July 2012

The uncoupling activity of oxyclozanide in warm blooded animals has been studied in whole animals, isolated tissue in vitro and on mitochondrial preparations. The onset of post mortem rigidity in mice and rats is accelerated and a contracture of striated muscle is produced. Oxyclozanide (1 μM) stimulated rat liver mitochondrial respiration and stimulated an ATP‐ase activity.
EFFECT OF ETHER ANAESTHESIA ON PHARMACOKINETICS OF N‐(2 HYDROXY ETHYL) 2‐PHENYL ETHYL CARBAMATE: INHIBITION OF ITS ENTEROHEPATIC CIRCULATION
Authors: OBIANWU HOPÉ O.
Published: July 2012

The effect of the ether anaesthesia on the plasma half‐life of N‐(2 hydroxy ethyl) 2‐phenyl ethyl carbamate has been studied in rats.

The plasma half‐life of the carbamate was considerably shorter in animals anaesthetized with ether prior to drug administration than in control rats.

The longer plasma half‐life of the carbamate in control animals was shown to be due to enterohepatic circulation.

Inhibition of this phenomenon by ether was responsible for the shorter plasma half‐life of the carbamate in animals anaesthetized with this agent before drug administration.

The possible mechanisms by which the ether‐induced effect is brought about are discussed.