bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic Transition in Central and Eastern Europe: Comparisons and Lessons
Authors: Balcerowicz Leszek
Published: January 2008

Abstract

There are three features which distinguish the global transition in Central and Eastern Europe: both economic and political systems are the focus of radical transformation, this institutional revolution has been largely peaceful, and a pluralistic political system emerged faster than capitalism in the economic sphere. The initial conditions, for example the inherited economic structure, the macroeconomic situation and the type of economic system, have an important impact upon the pace and effects of the subsequent market‐oriented reform. There are four important reasons why the state should concentrate its activity on the sphere of its natural competence. These reasons are even more important in economies of transition. The speed of the subordinate processes of transition differs which gives rise to important issues of phasing. Macroeconomic stabilisation, microeconomic liberalisation and privatisation should be implemented at a speed close to maximum. The Polish economic reform shows that a radical and comprehensive economic program introduced in an initially socialist economy, under extremely difficult macroeconomic conditions, can be successful in spite of powerful external shocks.
Absence Penalties and Work Attendance
Authors: Balchin Jeffrey , Wooden Mark
Published: January 2008

This article extends previous economic treatments of the work attendance decision by providing a more complete specification of the absence penalty function. In particular, the penalty for absence is modelled as a function of both the opportunity cost of dismissal for excessive absence and the level of threat of dismissal chosen by management to control absence. Moreover, since the probability of dismissal is itself a function of the absence rate, a simultaneous system is posited. Strong support for the model is found in workplace‐level data collected as part of the 1989–90 Australian Workplace Industrial Relations Survey.
Are Terms of Trade Rises Inflationary?
Authors: Gruen David , Dwyer Jacqueline
Published: January 2008

This article explores the relationship between the terms of trade and inflation. It shows, both analytically and empirically, that the exchange rate response to a change in the terms of trade is crucial to the inflation outcome. It demonstrates the existence of a ‘threshold’ exchange rate response. Our best estimate is that a rise in the terms of trade is inflationary if the associated rise in the real exchange rate is less than about 1/3–1/2 of the rise in the terms of trade. However, if appreciation of the real exchange rate is larger than this, the consequent fall in the domestic price of importables is large enough that the terms of trade rise reduces inflation, at least in the short run.
DIE ROTFÄRBUNG VON HOCHGEBIRGSSEE‐ORGANISMEN
Authors: BREHM Von V.
Published: January 2008

In Hochgebirgsseen treten auf der ganzen Erde wie auch in den Gewässern der Polarzone bei bestimmten Tiergruppen rote Pigmente auf, über deren Entstehung und Bedeutung im Laufe der letzten 50 Jahre verschiedene Ansichten geäussert wurden. Die elf hierüber aufgestellten Hypothesen werden in konkreten Fällen angeführt und zur Discussion gestellt, da keine dieser Annahmen experimentell gestützt ist und demnach alle der Nachprüfung von chemischer und physiologischer Seite bedürfen.

Red pigments are found in certain groups of animals occurring in mountain lakes in all parts of the world and in polar waters. In the course of the last half century various opinions have been expressed concerning the origin and significance of this red coloration. In this article eleven hypodieses have been reviewed. None of these has an experimental basis and all therefore require to be tested chemically and physiologically.
HORMONES IN CRUSTACEA
Authors: KLEINHOLZ L. H.
Published: January 2008

Colour changes in crustaceans are controlled by a secretion originating in the eye‐stalk. The glandular tissue is probably Hanström's sinus gland, although the X‐organ may also be concerned in this function. Retinal pigment migration is similarly regulated by a hormone from the eye‐stalks. Physiological evidence points to the existence of at least two pigmentary hormones, one for the chromatophores and another for the retinal pigment. No conclusion can yet be made concerning the exact numbers of these hormones. Cyclic activity of these pigmentary effectors under constant environmental conditions is explained on a nervous‐hormonal basis.

There is no evidence that calcium metabolism is under specific hormonal control. The reserve pre‐moulting calcium may be regulated by an eye‐stalk hormone that is also suspected of inhibiting ecdysis. The viability effect reputedly regulated by eye‐stalk hormone may be due to nervous injury rather than to a specific active substance.

Maintenance of the secondary sex characters has been thought to be controlled by the sex hormones. The evidence, coming chiefly from studies of parasitic and radiation castrations, is not wholly reliable because of metabolic disturbances introduced under these conditions. Direct evidence from injection of glandular extracts is lacking.
THE EVOLUTION OF EPIPHYSES AND OF ENDOCHONDRAL BONE
Authors: HAINES R. WHEELER
Published: January 2008

1. The most primitive type of epiphysial mechanism known is found in bony fishes, and from this type all others are easily derivable. The cartilaginous epiphyses contain a mass of undifferentiated cells, a growth zone of flattened cells, and a zone of hyper‐trophied cells derived from them. Endochondral bone and marrow are well developed. Temporary cessation of growth may occur with loss of differentiation in the growth zone and the formation of a closing plate of endochondral bone shutting off the marrow from the epiphysial cartilage.

2. In some modern fishes, Chondrostei and Dipnoi, endochondral bone and marrow have been lost, in others a secondary centre of calcification may be found in the epiphysis, but these changes are peculiar specializations.

3. In primitive tetrapods, including all typical early fossil forms and the living Crocodilia and Chelonia, the cells of the growth zone are arranged more or less regularly in columns, and the endochondral bone, guided by these columns, again has a regular arrangement.

4. Of the modern amphibians the Urodela have lost the regular arrangement of the cells of the growth cartilage, and have reduced the amount of their endochondral bone, while the Anura have developed a peculiar match‐head type of epiphysis with a calcified secondary centre.

5. In Sphenodon a large calcified secondary centre is developed between the articular cartilage and the growth cartilage. By separating these cartilages it allows each to adopt the most advantageous position, the one for the formation of the joint surface, and the other for directing the arrangement of the trabeculae of the endochondral bone.

6. All other groups are specialized in one direction or another. Bony secondary centres which strengthen the epiphyses are found in typical Lacertilia except in some small forms which have lost them, in the tibia of Aves and in Mammalia. Cartilage canals, developed primarily for the nutrition of the cartilaginous epiphyses, are found in Varanidae, Aves and Eutheria, and possibly in Anura, while the Monotremata have a very peculiar cartilage canal system whose development is not yet understood. These features are the result of very detailed parallelisms in evolution.

7. Intratendinous centres of ossification, formed by ossification of tendons where these are inserted into epiphysial cartilage, are distinguished structurally from typical epiphysial centres.
THE PRESENT STATUS OF THE NEURONE THEORY
Authors: NONIDEZ JOSÉ F.
Published: January 2008

During the last decade certain authors have considered the classical neurone theory to be obsolete and have resuscitated the long‐rejected hypothesis of a nervous syncytium, mainly on histological evidence. Bauer believes in connexions between embryonic neuroblasts, serving as pathways for the growth of nerve fibres which thus develop intraprotoplasmically. This concept must be regarded as entirely hypothetical. Anastomoses found between neuroblasts and nerve fibres growing in tissue culture are emphasized by the reticularists, but this is not overwhelmingly against the neurone theory since such anastomoses are by no means universal and they depend on the part of the nervous system cultured and on the properties of the medium. Claims by Bauer on the continuity of nerve cells with each other and with neuroglia disagree with the demonstrated existence of free dendrites and of synapses withneurones. Reticularists also maintain the continuity of neurones in the autonomic system, but this too is open to serious criticism on histological grounds. Moreover, autonomic ganglia afford good material for the demonstration of synaptic endings both in ‐fixed and living preparations. The reality of independent neurones is confirmed by the degeneration of synaptic boutons in the central nervous system after the destruction of nerve tracts, and by the degeneration and regeneration of preganglionic fibres in autonomic ganglia, in which the loss and recovery of function are confirmed experimentally. The existence of the synapse in confirmed by the delay in impulse transmission, varying with the type of synapse, and by the nicotine block to impulses from preganglionic fibres to autonomic ganglia. The recent criticisms of the neurone theory are based on preparations made exclusively by the Biel‐schowsky technique, unsupported by experimental work, and the several workers disagree widely in their evidence. Boeke claims that the finer divisions of the autonomic system contain a meshwork of neurofibrils clearly distinguishable from the surrounding connective tissue; this structure is not found, however, with other neurofibrillar methods but appears with silver carbonate which does not stain nervous structures. Stohr believes in a fine terminal reticulum of the autonomic and sensory systems surrounding every cell in the body. Again other competent histologists, working with techniques which do not stain connective tissue fibres, have failed to confirm Stohr, whose claims are moreover unsupported experimentally. The reticularists cannot agree among themselves on their substitute for the neurone theory and it would seem wise to retain this concept until better proof is offered of the syncytial nature of the nervous system.
PIGMENTS IN THE COELENTERATA
Authors: FOX D. L. , PANTIN C. F. A.
Published: January 2008

(i) The nature, variety and significance of coelenterate pigments is discussed. They may be grouped under: miscellaneous pigments, the pyrrolic series, purines, melanins, carotenoids. (2) The nature of several well‐known pigmentations is not fully understood. Chief of these are the deep blues and browns of pelagic coelen‐terates, possibly due to carotenoid‐protein compounds; and the remarkable stable colours of the spicules of Alcyonaria. The latter appear to be combined with calcium and iron. (3) Of the pyrrolic series haematins are common. They play little part in coloration and are probably simply part of the intracellular respiratory system. Bile pigments also occur and attention is drawn to the interesting pigment of this kind present inCalliactis parasitica.(4) Purines only contribute white to the colour pattern of some anemones. They occur as uric acid and possibly as other purines. (5) Black and brown melanins occur inMetridium senileand probably in other anemones. Even white anemones may possess a complete tyrosinase system. (6) It seems that coelenterate colours are due chiefly to carotenoids. These are found in species from all parts of the phylum. Though the evidence is incomplete, the carotenoids are in some cases known to be derived from the food (Hydra, actinians). Sometimes at least, however, they are altered to ‘animal’; carotenoids, as in the ‘metridene’ fromMetridium.Different colour varieties may form chemically different carotenoids. (7) Detailed study of actinians shows a surprisingly complex pigment situation. An individual may possess several distinct carotenoids, and different varieties of the same species are characterized by different series of pigments. (8) Little is known of the biochemical significance of the pigments. There are indications that the presence of carotenoids is in some cases related to light intensity. There is also evidence that these pigments are of importance in gamete formation and in regeneration. The biochemical significance of the varietal colour differences is not known. Attention is drawn to Stephenson's observations on the importance of range of colour and of colour pattern in relation to morphological axes of differentiation. (9) The genetic significance of the existence of colour varieties is discussed. True polymorphism with respect to colour is common in coelenterates. No genetic explanation can be offered without further experiment. The resemblance of the colour systems ofMetridiumto the blood group systems in man is commented on. Attention is drawn to the widespread character of colour polymorphism in the lower invertebrates.
PREDATOR VIGILANCE AND GROUP SIZE IN MAMMALS AND BIRDS: A CRITICAL REVIEW OF THE EMPIRICAL EVIDENCE
Authors: ELGAR MARK A.
Published: January 2008

One commonly cited benefit to animals that forage in groups is an increase in the probability of detecting a predator, and a decrease in the time spent in predator detection. A mathematical model (Pulliam 1973) predicts a negative relationship between group size and vigilance rates. Over fifty studies of birds and mammals report a negative correlation between group size and vigilance behaviour and most conclude that the relationship at least partly explains why individuals forage in groups. This review evaluates the strength of these conclusions based on their evidence. Those variables that may confound the relationship between vigilance and group size are outlined, and their control is assessed for each study. The variables I consider to be important include the density and type of food; competition between individuals; the proximity to both a safe place and the observer; the presence of predators; the visibility within the habitat; the composition of the group; the ambient temperature and the time of day. Based on these assessments, most of the studies fail to adequately demonstrate an unambiguous relationship between vigilance behaviour and group size. Nevertheless, many studies reveal interesting features of the relationship between vigilance and group size that should provide fruitful avenues for future research.
DIFFERENCES IN THE FORAGING OF JUVENILE AND ADULT BIRDS: THE IMPORTANCE OF DEVELOPMENTAL CONSTRAINTS
Authors: MARCHETTI KAREN , PRICE TREVOR
Published: January 2008

Juvenile birds differ from conspecific adults in their diet and methods of prey capture and prey handling. Juvenile‐adult differences in foraging result from (1) immaturity of the beak, skeleto‐muscular and neurological systems and (2) the time required to learn foraging skills. These conclusions are largely based on field observations. More experimental studies to assess the relative importance of the various constraints are needed.

Juvenile birds appear to be under strong selection to reach adult form and function as rapidly as possible. Remaining differences between juveniles and adults are largely attributable to constraints. In contrast to many other taxa there are few examples in which juvenile‐adult differences in foraging have been accentuated by selection on the juvenile behaviours.
THE INFLUENCE OF BENSERAZIDE ON CHANGES IN MONOAMINE OXIDASE ACTIVITY IN SOME RAT TISSUES FOLLOWING TREATMENT WITH L‐DOPA
Authors: CALLINGHAM B. A. , LYLES G. A.
Published: January 2008

This study was designed to see whether or not increases in monoamine oxidase (MAO) specific activity that follow chronic treatment of rats with L‐dihydroxyphenylalanine (L‐DOPA) could be modified by benserazide (Ro 4‐4602), an inhibitor of L‐aromatic amino acid decarboxylase, and to compare the properties of the increased MAO activity with those of control animals.

Male Wistar rats were treated with L‐DOPA (250 mg/kg) and benserazide (40 mg/kg) either alone or in combination for 10 days.

The activity of MAO in homogenates of heart, kidney, liver and brain was measured with 5‐hydroxytryptamine (5‐HT) and benzylamine (BZ).

The significant increases in MAO specific activity seen in heart and kidney following L‐DOPA treatment could be reduced or prevented by benserazide.

Use of the selective MAO inhibitor clorgyline showed that the increases in MAO specific activity, when measured with either 5‐HT or BZ were due to an increase in the number of active centres of MAO‐A, in the rat heart.

There was a significant increase in the V max of the enzyme reaction with 5‐HT, in the rat heart and kidney homogenates.

It is concluded that L‐DOPA increases the specific activity of MAO‐A in rat heart and kidney as a result of its decarboxylation.
THE EFFECTS OF SOME DOPAMINE ANTAGONISTS ON CHOLINERGIC MECHANISMS IN THE GUINEA‐PIG ILEUM
Authors: FOSBRAEY P. , HIRD M. F. , JOHNSON E. S.
Published: January 2008

Activation of prejunctional muscarinic and opiate receptors on cholinergic neurones of the guinea‐pig ileum by acetylcholine (ACh) or morphine was seen as an inhibition of twitch responses to transmural electrical stimulation. These inhibitory responses were antagonised by metoclopramide and DL308‐IT but no other antagonist used blocked the morphine responses apart from sulpiride in very high concentrations (100 μM and above).

Prejunctional and postjunctional responses to ACh on the guinea‐pig ileum were measured in the presence of increasing concentrations of some muscarinic and dopamine antagonists. Atropine, hyoscine, chlorpromazine, cis‐flupenthixol and thioridazine showed no selectivity in their antagonism of either response to ACh. Benzhexol selectively antagonised the postjunctional response whereas metoclopramide and DL308‐IT showed greater selectivity for the prejunctional effect which they antagonised competitively. Sulpiride, a compound chemically related to metoclopramide, blocked neither the prejunctional nor postjunctional ACh responses. Clozapine antagonised the postjunctional ACh responses whilst apparently potentiating the prejunctional inhibition by ACh.

It was concluded that pharmacological differences may exist between prejunctional and postjunctional muscarinic receptors for ACh and that the antipsychotic actions of dopamine antagonists are unlikely to involve blockade of prejunctional ACh or opiate receptors.
EFFECTS ON BLOOD PRESSURE OF NORADRENALINE AND ISOPRENALINE ADMINISTERED INTO THE THIRD VENTRICLE OF THE BRAIN OF ANAESTHETIZED AND CONSCIOUS CATS
Authors: DAY M. D. , POYSER R. H. , SEMPIK J.
Published: January 2008

Noradrenaline administered into the third ventricle of the brain (IIIv) of both conscious and anaesthetized cats induced increases in blood pressure accompanied by small and variable heart rate effects. The pressor responses were reduced after autonomic ganglion blockade indicating their likely central origin.

Noradrenaline when administered either into a lateral cerebral ventricle (i.c.v.) in conscious and anaesthetized cats or into the cisterna magna (i.c.) in anaesthetized cats induced falls in blood pressure accompanied by bradycardia.

Pressor responses to IIIv noradrenaline in conscious cats were partly blocked by either propranolol or thymoxamine indicating a possible involvement in the responses of excitatory adrenoreceptors of both α and β types.

Pressor responses induced by IIIv isoprenaline in conscious cats were blocked by propranolol but not by thymoxamine suggesting the effect is mediated solely via excitatory β‐adrenoreceptors.

In anaesthetized cats prior i.c. administration of noradrenaline reduced the pressor responses induced by IIIv noradrenaline.

In conscious cats i.v. clonidine reduced pressor responses to IIIv noradrenaline without depressing peripheral vascular noradrenaline sensitivity.

The results suggest the involvement of excitatory and inhibitory α‐adrenoreceptors and of excitatory β‐adrenoreceptors in central blood pressure control. It is also concluded that activation of inhibitory α‐adrenoreceptors in the hind brain region can suppress the cardiovascular effects of stimulating excitatory α‐ and β‐adrenoreceptors located in the region of the third ventricle.
FACTORS INFLUENCING THE MAGNITUDE AND DURATION OF RESPONSES TO ENDOGENOUS AND EXOGENOUS NORADRENALINE IN RABBIT PULMONARY ARTERY AND PORTAL VEIN
Authors: PATON D. M.
Published: January 2008

In the rabbit portal vein, cocaine potentiated responses to (–)‐noradrenaline, and prolonged relaxation following transmural stimulation. Neither process was altered by hydrocortisone and U‐0521, oxytetracycline or 4‐aminopyridine alone or in combination with cocaine. These findings indicated that neuronal uptake was principally responsible for the inactivation of noradrenaline in this tissue.

In the rabbit pulmonary artery, the rate of relaxation following transmural stimulation was prolonged by cocaine and by hydrocortisone and U‐0521, and further prolonged by the combination of all three drugs. These findings suggest that both neuronal and extra‐neuronal uptake are responsible for the inactivation of noradrenaline in this tissue.

4‐Aminopyridine potentiated responses to (–)‐noradrenaline and prolonged relaxation after transmural stimulation in pulmonary artery possibly as a consequence of a postjunctional action in this tissue.

The rabbit portal vein was less sensitive to (–)‐noradrenaline and relaxed more after transmural stimulation than the pulmonary artery. It is suggested that this reflects the denser noradrenergic innervation and smaller neuromuscular distance present in the portal vein.
THE USE OF THE RAT RIGHT VENTRICLE STRIP IN STUDIES ON NORADRENERGIC TRANSMISSION
Authors: DOGGRELL SHEILA A. , VINCENT LYNN
Published: January 2008

The possibility of using contractility studies with the rat right ventricle strip to assess the effects of drugs on all aspects of noradrenergic transmission has been examined.

The force of the contractile responses to field stimulation at 0.5 and 2, but not 5 Hz, markedly decreased with time. About 55% of the tissues responded directly to (−)‐isoprenaline, 1 × 10−6M (123 tissues from 220 tested) in the absence of other stimuli. In these tissues the force of the contractile responses remained constant and the rate increased with time. Thus it is essential to provide time controls in studies with rat right ventricle.

Under conditions in which the responses to (−)‐isoprenaline, 1 × 10−6M, alone were unaffected the responses to field stimulation at 5 Hz were inhibited by 66 and 86% by 9 × 10−6M tetrodotoxin and 1 × 10−5M guanethidine, respectively. (+)‐Propranolol and timolol (both at 1 × 10−6M), but not phentolamine, 1 × 10−6M, inhibited responses to (−)‐isoprenaline, 1 × 10−6M alone and responses to field stimulation at 5 Hz. This demonstrates that the responses to field stimulation are largely due to activation of noradrenergic nerves, the released noradrenaline acting at postsynaptic β‐adrenoreceptors.

Although nortriptyline is a potent inhibitor of the neuronal uptake of noradrenaline, at 1 × 10−6M it had no effect on the contractile responses to field stimulation at 5 Hz and inhibited responses to (−)‐isoprenaline, 1 × 10−6M, alone and at a higher concentration (1 × 10−5M) nortriptyline abolished both responses. It is suggested that the rat right ventricle preparation may be useful in examining the effects of drugs on noradrenergic transmission in the heart.
CENTRAL CATECHOLAMINERGIC LESIONS IN THE DEVELOPING RAT: EFFECTS ON CARDIAC NORADRENALINE LEVELS, TURNOVER AND RELEASE
Authors: DESKIN R. , SLOTKIN T. A.
Published: January 2008

The role of the central nervous system in regulating cardiac sympathetic tone was examined in developing rats with neonatal central catecholaminergic lesions produced by intracisternal 6‐hydroxydopamine treatment.

Lesioned animals showed a persistent deficit in both cardiac noradrnaline levels and spontaneous turnover rate as evaluated by alpha‐methyl‐p‐tyrosine treatment.

Despite these deficits, tyramine was fully capable of releasing cardiac noradrenaline and short‐term centrally‐mediated release also could be elicited by exposure to cold or by swimming exercise.

The alterations in cardiac noradrenaline content produced by the central lesions may result from long‐term reductions in sympathetic tone which do not necessarily compromise short‐term response capabilities of the sympathetic system.
THE RELEASE OF ENDOGENOUS CATECHOLAMINES IN THE CAT HYPOTHALAMUS IS AFFECTED BY SPINAL TRANSECTION AND DRUGS WHICH CHANGE THE ARTERIAL BLOOD PRESSURE*
Authors: DIETL H. , EISERT A. , KRAUS A. , PHILIPPU A.
Published: January 2008

In anaesthetized cats, posterior and anterior hypothalamic areas were superfused with CSF through double‐walled cannulae. The release of endogenous catecholamines (dopamine, noradrenaline and adrenaline) was determined in the superfusate by a radioenzymatic assay.

Transection of the brain caudal to the hypothalamus almost abolished the release of catecholamines in the posterior hypothalamic area, while that in the anterior hypothalamic area was moderately decreased. A circular transection around the hypothalamus greatly reduced the release of catecholamines in the anterior hypothalamic area. It is concluded that the catecholaminergic nerve endings of the anterior hypothalamic area do not originate entirely from cell bodies located in the brain stem.

Spinal transection elicited a pressor response which was followed by a fall of the arterial blood pressure. The pressor response was associated with increased rates of release of the catecholamines in the anterior hypothalamic area, while the release of catecholamines in the posterior hypothalamic area was reduced. The fall of blood pressure enhanced the rates of release of the catecholamines in the posterior hypothalamic area and reduced their release in the anterior hypothalamic area.

Chlorisondamine i.v. caused a fall of blood pressure which was associated with an increased release of catecholamines in the posterior hypothalamic area and a decrease in the rates of release in the anterior hypothalamic area whilst i.v. tramazoline elicited a pressor response and enhanced the rates of release of the catecholamines in the anterior hypothalamic area.

It is concluded that pronounced changes in the arterial blood pressure affect the release of catecholamines in opposite direction in the two hypothalamic areas to counteract the blood pressure change.
BETA‐ADRENORECEPTORS OF THE CAT NICTITATING MEMBRANE
Authors: VARMA D. R. , NICKERSON M.
Published: January 2008

The relaxant effects of isoprenaline, salbutamol, adrenaline and noradrenaline on the partially contracted isolated nictitating membrane of the cat were determined in the absence and the presence of α‐adrenoreceptor blockade.

It was possible to demonstrate significant relaxant effects of isoprenaline and salbutamol in the absence as well as in the presence of α‐adrenoreceptor blockade. However, the relaxant effects of adrenaline and noradrenaline could not be demonstrated in the absence of α‐adrenoreceptor blockade.

Molar concentrations (EC30) of isoprenaline, salbutamol and adrenaline causing 30% relaxation of the tone did not significantly differ from each other; EC30 of each of these agents was significantly less than that of noradrenaline.

β1‐Adrenoreceptor antagonist metoprolol was less potent than β2‐antagonist H 35/25 in antagonizing the effect of salbutamol; metoprolol was more potent than H 35/25 in antagonizing noradrenaline. Both these agents were effective antagonists of isoprenaline; however, metoprolol and H 35/25 in combination produced greater antagonism of isoprenaline than did each antagonist separately.

It is concluded that the cat nictitating membrane possesses both β1‐ and β2‐adrenoreceptors which are responsible for the relaxant effects of sympathomimetic agents. A study of these receptors is, however, complicated by concomitant stimulation of α‐adrenoreceptors.
PHARMACOLOGICAL INVESTIGATION OF α‐ADRENORECEPTORS IN GUINEA‐PIG SPLENIC CAPSULE
Authors: DIGGES K. G. , McPHERSON G. A. , SUMMERS R. J.
Published: January 2008

A study has been made of α‐adrenoreceptors in the smooth muscle of the guinea‐pig splenic capsule.

In this preparation, noradrenaline (NA), adrenaline (Adr) and α‐methyl‐NA were full agonists, while phenylephrine, dopamine and the catechol‐imidazolidine (3,4‐dihydroxyphenylamino)‐2‐imidazolidine, (DPI) were partial agonists.

The imidazolidines clonidine and oxymetazoline showed no agonist activity, but both inhibited the agonist activity of NA. pA2 values calculated from Arunlakshana and Schild plots were 6.88 and 6.95 for clonidine and oxymetazoline respectively. Slopes of the Schild plots were close to unity, indicating competitive antagonism.

The α‐adrenoreceptor antagonists phentolamine, prazosin and yohimbine also inhibited the agonist activity of NA with mean pA2 values of 8.32, 9.22 and 6.90 respectively. Slopes of Schild plots were significantly less than 1, suggesting that the inhibition was not truly competitive in nature.

The irreversible α‐adrenoreceptor antagonist phenoxybenzamine at low concentrations (10–9M) shifted the log concentration‐response curve to NA to the right and greatly reduced the maximum response.

It is suggested that the adrenoreceptors in the guinea‐pig splenic capsule are probably of the α1‐type, and that this tissue possesses relatively few spare receptors.
HYPOTHALAMIC SUPERFUSION WITH HISTAMINE AGONISTS AND ANTAGONISTS MODIFIES THE PRESSOR RESPONSE TO HYPOTHALAMIC STIMULATION*
Authors: PHILIPPU A. , WIEDEMANN K.
Published: January 2008

To investigate the effect of hypothalamic application of histamine agonists and antagonists on the pressor response to hypothalamic stimulation, the posterior hypothalamus of anaesthetized cats was superfused with drugs through a push‐pull cannula and electrically stimulated with the non‐insulated tip of the cannula.

Superfusion of the posterior hypothalamic area with histamine enhanced the pressor response to hypothalamic stimulation. The most pronounced effect of histamine was found, when the caudal region of the posterior hypothalamic area was superfused. The enhancing effect of histamine was abolished when the hypothalamus was pre‐superfused with metiamide; it was slightly inhibited by pre‐superfusion with mepyramine.

Dimaprit also enhanced the pressor response to hypothalamic stimulation; the effect of this drug was abolished by metiamide, whilst hypothalamic pre‐superfusion with mepyramine was ineffective.

Superfusion of the hypothalamus with 2‐methylhistamine did not change the pressor response to hypothalamic stimulation.

The enhancing effect of histamine was abolished by hypothalamic pre‐superfusion with phentolamine, phenoxybenzamine or propranolol.

It is concluded that histamine enhances the pressor response to hypothalamic stimulation mainly by acting on H2‐receptors of the posterior hypothalamus. The inhibition of the effect of histamine by α‐and β‐adrenoreceptor blocking agents indicates the involvement of catecholaminergic systems of the hypothalamus.
PHARMACOLOGICAL CHARACTERISTICS OF SPINAL α‐ADRENORECEPTORS IN RATS
Authors: CONNOR HELEN E. , DREW G. M. , FINCH L. , HICKS P. E.
Published: January 2008

Spinal α‐adrenoreceptors involved in cardiovascular control have been investigated using selective α‐adrenoreceptor agonists and antagonists in urethane‐anaesthetized rats.

Intrathecal injections of clonidine, α‐methylnoradrenaline, guanfacine and M7 at the C7‐T1 level reduced blood pressure and heart rate. In contrast, phenylephrine, 5‐hydroxytryptamine and procaine had little or no effect. These results suggest the involvement of spinal α2‐adrenoreceptors.

The fall in blood pressure produced by clonidine appeared to be attributable to a reduction in heart rate and stroke volume. Lower body vascular resistance was unchanged.

The clonidine‐induced bradycardia was antagonised by prazosin, WB4101, piperoxan or yohimbine. Their relative potencies suggest that α1‐ rather then α2‐adrenoreceptors mediate this response.

Piperoxan and yohimbine clearly prevented the clonidine‐induced fall in blood pressure; prazosin and WB4101 also appeared to antagonise clonidine but these results were complicated by the fact that these antagonists themselves reduced blood pressure.

It was difficult to interpret these results simply in terms of α1‐ or α2‐adrenoreceptors. Thus spinal α‐adrenoreceptors may be different from peripheral α1‐ or α2‐adrenoreceptors.
STUDIES ON THE PRE‐ AND POSTJUNCTIONAL ACTIVITIES OF α‐ADRENORECEPTOR AGONISTS AND THEIR CARDIOVASCULAR EFFECTS IN THE ANAESTHETIZED RAT
Authors: DOXEY J. C. , FRANK LEONIE W. , HERSOM A. S.
Published: January 2008

The selectivity of a number of agonists for peripheral α1‐ and α2‐ adrenoreceptors was determined and related to their cardiovascular effects in pentobarbitone‐anaesthetized rats.

In isolated tissues, presynaptic α2‐ and postsynaptic α1‐adrenoreceptor activity was determined on the rat vas deferens and anococcygeus muscle respectively. Xylazine, guanabenz, guanoxabenz and guanfacin were more selective, whilst lofexidine, tiamenidine, naphazoline, oxymetazoline and St 91 were less selective than clonidine for presynaptic α2‐adrenoreceptors.

The anococcygeus muscle of the pithed rat was used to determine the α‐adrenoreceptor selectivity of the compounds in vivo. The selectivities were similar to those obtained in vitro.

Following intravenous administration to pentobarbitone‐anaesthetized rats guanabenz and guanfacin caused small transient pressor responses and a prolonged secondary hypotension. In contrast oxymetazoline and St 91 produced marked initial pressor responses and the secondary reduction in blood pressure was absent. Clonidine and tiamenidine produced marked initial pressor responses followed by secondary hypotensive effects. All compounds reduced heart rate.

Intracerebroventricular (i.c.v.) administration of clonidine, guanabenz and guanfacin elicited falls in blood pressure and heart rate. In contrast blood pressure was either unaffected or elevated following i.c.v. administration of St 91, oxymetazoline and tiamenidine.

It is concluded that in the normotensive rat, central α2‐adrenoreceptors play a major role in the hypotensive effects of clonidine and related compounds.
RELEASE OF 3H‐ADRENALINE FROM AN ISOLATED INTACT PREPARATION OF THE RABBIT ADRENAL GLAND: NO EVIDENCE FOR RELEASE MODULATORY α‐ADRENORECEPTORS
Authors: COLLETT A. R. , STORY D. F.
Published: January 2008

The possibility that catecholamine secretion from the rabbit adrenal gland is subject to modulation by a mechanism involving α‐adrenoreceptors was investigated in an isolated preparation of the gland.

Intact left adrenal glands from the rabbit were perfused with Krebs‐Henseleit solution through their vasculature. The adrenal catecholamine stores were radiolabelled with 3H‐adrenaline and subsequently, efflux of the radiolabel was elicited by stimulation of an attached segment of splanchnic nerve (60 s at 5 Hz). In some experiments, efflux of radiolabel was elicited by perfusion with potassium‐enriched Krebs‐Henseleit solution (30 mM).

Radioactivity released in response to nerve stimulation was accounted for almost entirely by (3H)‐adrenaline. Stimulation‐induced (S‐I) efflux was abolished by 0.1 μM tetrodotoxin and by omission of calcium from the perfusion medium and was reduced by approximately 55% by 100 μM hexamethonium.

S‐I efflux was enhanced to approximately 150% of control S‐I efflux in the presence of 10μM phenoxybenzamine; however, 3 μM phentolamine and yohimbine in concentrations of 0.1 and 1.0 μM had no effect; in a higher concentration (10μM) yohimbine reduced S‐I efflux by approximately 50%. It is likely that the effect of phenoxybenzamine in enhancing S‐I efflux is due to blockade of reuptake of 3H‐adrenaline since cocaine (30 μM) enhanced release to a similar extent.

S‐I efflux was not altered in the presence of the α‐adrenoreceptor agonists noradrenaline (0.1 μM), clonidine (1 μM) or oxymetazoline (10 μM).

Release of radiolabel evoked by perfusion with 30 mM potassium solution was unaltered in the presence of phentolamine (3 μM) or clonidine (1 μM).

These findings do not support the existence in the rabbit adrenal gland of a mechanism involving α‐adrenoreceptors through which catecholamine secretion may be modulated.
FUNCTIONAL ROLE OF CARDIAC PRESYNAPTIC α2‐ADRENORECEPTORS IN THE BRADYCARDIA OF α‐ADRENORECEPTOR AGONISTS IN PENTOBARBITONE‐ AND URETHANE‐ANAESTHETIZED NORMOTENSIVE RATS
Authors: DE JONGE A. , SANTING P. N. , TIMMERMANS P. B. M. W. M. , VAN ZWIETEN P. A.
Published: January 2008

The relative potencies of 6 α‐adrenoreceptor agonists, with differing physicochemical properties, at cardiac presynaptic α‐adrenoreceptors were determined by measuring their ability to reduce the tachycardia produced by stimulation of the cardiac sympathetic nerves in pithed rats. The compounds studied were clonidine, B‐HT 933 (azepexole), oxymetazoline, St 91, naphazoline and DPI.

The bradycardia produced by the same compounds in bilaterally vagotomized, urethane‐ or pento‐barbitone‐anaesthetized normotensive rats were also compared. The relative order of presynaptic potency appeared similar to that observed for the bradycardic activity of the compounds in urethane‐ and pento‐barbitone‐anaesthetized rats. In pentobarbitone‐anaesthetized rats all compounds evoked a maximal effect of 18–20% reduction in heart rate. In urethane‐anaesthetized rats, however, a difference was observed between clonidine and azepexole on the one hand and oxymetazoline, St 91, naphazoline and DPI on the other hand. The former induced a 20–22% reduction in cardiac frequency, whereas the latter diminished heart rate by 10–16% only. In vagotomized, bilaterally adrenalectomized, urethane‐anaesthetized rats, clonidine, St 91, naphazoline and azepexole evoked a 25% reduction in heart rate, whereas a 20% reduction was observed for DPI and oxymetazoline.

A radio‐enzymatic determination of plasma catecholamines demonstrated that under urethane‐anaesthesia plasma adrenaline concentrations were significantly elevated over the values observed in pentobarbitone‐anaesthetized rats. This rise in plasma adrenaline was related to the amount of urethane used. In urethane‐anaesthetized, bilaterally adrenalectomized rats, plasma adrenaline was not significantly elevated.

These findings demonstrate the involvement of cardiac presynaptic α2‐adrenoreceptors in the acute bradycardia, evoked by the α‐adrenoreceptor agonist upon intravenous application to pentobarbitone‐anaesthetized, normotensive rats. In urethane‐anaesthetized rats, however, the functional role of the cardiac presynaptic α2‐adrenoreceptors may be obscured as a result of the high plasma adrenaline levels observed in these animals.
PRESYNAPTIC DOPAMINE RECEPTORS MEDIATE THE INHIBITORY ACTION OF DOPAMINE AGONISTS ON STIMULATION‐EVOKED PRESSOR RESPONSES IN THE RAT
Authors: CLAPHAM J. C. , HAMILTON T. C.
Published: January 2008

1 The effects of the dopamine agonists TL‐99, M‐7 (N, N‐dimethyl analogues of aminotetralins) and N, N‐dinpropyldopamine (NNPD) on stimulation‐evoked pressor responses and tachycardia in pithed Sprague‐Dawley rats were investigated when pressor responses to the compounds per se had subsided. Various antagonists were used to characterise the effects of the dopamine agonists.

2 M‐7 (3 μg/kg i.v.) and NNPD (1 mg/kg i.v.), but not TL‐99 (1–30 μg/kg i.v.), inhibited pressor responses evoked by low frequency electrical stimulation of the spinal cord in the pithed rat.

3 M‐7 (3 μg/kg i.v.), but neither NNPD (1 mg/kg i.v.) nor TL‐99 (1–30 μg/kg), inhibited tachycardia evoked by low frequency electrical stimulation of the spinal cord in the pithed rat.

4 The inhibition of stimulation‐evoked pressor responses by M‐7 and NNPD was prevented by pimozide, metoclopramide and sulpiride but not by yohimbine, atropine, cimetidine or propranolol.

5 The inhibition of stimulation‐evoked tachycardia by M‐7 was prevented by yohimbine (and to a certain extent by sulpiride) but not pimozide, metoclopramide, atropine or cimetidine.

6 Pressor responses elicited by TL‐99, M‐7 and NNPD were selectively antagonised by yohimbine, but not by prazosin, indicating that these responses were mediated by stimulation of vascular postsynaptic α2‐adrenoreceptors.

7 This study demonstrates that, in the rat, presynaptic dopamine receptors exist on sympathetic pre‐ or postganglionic nerve endings to blood vessels, but not on sympathetic pre‐ or postganglionic nerve endings to the heart, where inhibition by M‐7 of stimulation‐evoked tachycardia is mediated by stimulation of presynaptic α2‐adrenoreceptors.
POSITIVE CHRONOTROPIC RESPONSES PRODUCED BY α‐ADRENORECEPTORS IN THE PITHED RAT
Authors: TUNG L‐H. , RAND M. J. , DRUMMER O. H. , LOUIS W. J.
Published: January 2008

Phenylephrine (1–100 γg/kg, intravenously) produced dose‐dependent increases in heart rate and blood pressure in the pithed rat.

The positive chronotropic response to phenylephrine (10 μg/kg) was reduced in a dose‐dependent manner by propranolol (0.01–0.3 mg/kg), but higher doses of propranolol (up to 3 mg/kg) did not reduce the response by more than about 50%. The residual response was virtually abolished by phentolamine (0.3 mg/kg) or prazosin (3 μg/kg). Labetalol (3 mg/kg) which has both α‐ and β‐blocking activity, also abolished the positive chronotropic response.

The pressor response to phenylephrine (1–30 μg/kg) was enhanced by propranolol (1 mg/kg) and abolished by phentolamine (1 mg/kg) and prazosin (30 μg/kg). Labetalol (3 mg/kg) reduced the response to phenylephrine by 73%.

Propranolol (0.3 mg/kg) completely blocked the chronotropic and vasodepressor effects of isoprenaline (0.1 μg/kg).

It is concluded that phenylephrine acts on both α1‐ and β1‐adrenoreceptors to produce an increase in heart rate, on α1‐adrenoreceptors to produce vasoconstriction and on β2‐adrenoreceptors to produce vasodilation. This latter effect is usually masked by the predominant vasoconstrictor action.
ANALYSIS OF THE ANTAGONISM BY PRAZOSIN OF NORADRENALINE AND PHENYLEPHRINE INDUCED CONTRACTIONS OF THE RAT ANOCOCCYGEUS MUSCLE*
Authors: ADENEKAN O. O. , TAYO F. M.
Published: January 2008

Blockade of α‐adrenoreceptors was analyzed with prazosin in the rat anococcygeus muscle contracted with noradrenaline (NA) and phenylephrine (PHE).

Prazosin (1.1 times 10–8– 8.8 times 10–7M) competitively blocked phenylephrine‐induced contractions (pA2= 8.93 ± 0.04, slope = 0.85 ± 0.07) whilst its antagonism of NA was non‐competitive (pA2= 8.45 ± 0.04, slope = 0.46 ± 0.03).

At higher concentrations, (1.76 times 10–5– 5.28 times 10–6M) prazosin competitively antagonized NA‐induced contractions (pA2= 7.58 ± 0.11, slope = 0.93 ± 0.09).

Phentolamine also reduced the effect of NA competitively (pA2= 8.11 ± 0.09, slope = 0.82 ± 0.26).

It is concluded that low concentrations of prazosin selectively blocked an α1‐adrenoreceptor component of NA‐mediated response whilst higher concentrations of prazosin non‐selectively blocked both α1‐ and α2‐adrenoreceptors.
DESENSITIZATION OF β‐ADRENORECEPTORS IN GUINEA‐PIG TRACHEA: A PROSTAGLANDIN MEDIATED PHENOMENON
Authors: BERTI F. , DAFFONCHIO L. , FOLCO G. C. , OMINI C. , VIGANO T.
Published: January 2008

The formation and release of PGE2‐like material (PGE2‐lm) from guinea‐pig isolated trachea and human bronchi following relaxation with isoprenaline (I) was investigated.

When airway smooth muscle precontracted with pilocarpine is relaxed by I, PGE2‐lm is released in the bathing fluid. Under conditions of β‐adrenoreceptor desensitization, a greater amount of PGE2‐lm is formed and the responsiveness of guinea‐pig tracheal spirals to cumulative doses of I is diminished.

Inhibition of cyclo‐oxygenase with indomethacin does not modify the relaxation induced by I but prevents the occurrence of refractoriness to I as well as formation and release of PGE2‐lm. Addition of exogenous PGE2 to guinea‐pig tracheas which were treated with indomethacin is able to restore the capacity of I to cause tachyphylaxis.

It is concluded that PGE2 which does not mediate the relaxation induced by I in airway smooth muscle, is responsible for the onset of desensitization of the β‐adrenoreceptor.
MODULATION BY β‐ADRENORECEPTORS OF SPONTANEOUS CONTRACTIONS OF RAT URINARY BLADDER
Authors: MAGGI C. A. , MELI A.
Published: January 2008

Propranolol (0.1 mg/kg i.v.) but not metoprolol (0.2 mg/kg i.v.) pretreatment increased the spontaneous motility triggered by progressive filling of rat urinary bladder without a concomitant effect on bladder capacity, except at high filling volumes. Compared to controls, the spontaneous motility of urinary bladder in propranolol pretreated rats displayed a higher frequency, indicating the existence of a tonic sympathetic inhibition.

β‐adrenoreceptor stimulation by isoprenaline (0.1–10 μg/kg i.v.) or terbutaline (0.1–1 mg/kg i.v.) in vivo produced a dose dependent inhibition of bladder spontaneous motility which was antagonized by propranolol (0.1 mg/kg i.v.) but not by metoprolol (0.2 mg/kg i.v.). Propranolol (0.2 mg/kg i.v.) pretreatment did not antagonize the inhibition of bladder motility produced by intravenous papaverine (0.5 mg/kg).

Propranolol (0.1 mg/kg i.v.) significantly antagonized the isoprenaline‐induced tachycardia (β1 mediated) and fall in diastolic blood pressure (β2 mediated) while metoprolol (0.2 mg/kg i.v.) antagonism was confined to β1 mediated responses.

Isoprenaline (0.25–1.5 μM) inhibited in a concentration dependent manner field stimulation induced contractions of rat detrusor muscle strips as did tetrodotoxin (0.5 μM). Hexamethonium (50 μM) had no inhibitory effect.

Our in vivo findings support the view that β2‐adrenoreceptors are responsible for modulating bladder motility mainly by suppressing the onset of spontaneous contractions.
A COMPARISON OF THE MUSCARINIC ANTAGONIST ACTIONS OF PANCURONIUM AND ALCURONIUM
Authors: DALTON D. W. , TYERS M. B.
Published: January 2008

In the pithed rat, muscarine (2.5–10μg/kg i.v.) normally produced bradycardias, but tachycardias were seen in the presence of pancuronium (0.1–1.0mg/kg i.v.) and alcuronium (0.1–5.0mg/kg i.v.).

The tachycardia was probably a result of muscarinic receptor stimulation, because it was antagonized by atropine (10μg/kg i.v.) and pirenzepine (10–30μg/kg i.v.). The location of these muscarinic receptors is probably within the sympathetic ganglia since the tachycardias were inhibited by pretreatment with propranolol (1mg/kg i.v.) or reserpine (5mg/kg i.p. 24 h prior to study).

In the rat isolated atria preparation, pancuronium was 86 times more potent as an antagonist of the effects of muscarine than in the rat isolated superior cervical ganglion. The mechanism of action in both tissues may be non‐competitive.

Pancuronium selectivity antagonized atrial inhibitory muscarinic responses compared to excitatory muscarinic responses in sympathetic ganglia in the rat.