bluuebunny/crossref_metadata_2025_split huggingface dataset:
CLONIDINE DEPENDENCE IN THE GUINEA‐PIG ISOLATED ILEUM
Authors: COLLIER HARRY O.J. , CUTHBERT NIGEL J. , FRANCIS DAVID L. 
Published: July 2012

Compared with the response of preparations incubated in solutions without clonidine, a three to four fold increase in the magnitude of the contracture of the longitudinal muscle to challenge with phentolamine (1.0 μm) was induced by incubating the guinea‐pig isolated ileum at 22°C for 24 h with clonidine (1.0 μm) in Krebs solution containing hexamethonium (70μm). Incubation of the ileum with clondine (1.0 μm) for 0.5 h at 37°C did not increase responsiveness to phentolamine.
The increase in responsiveness to phentolamine was directly related to the clonidine concentration in the incubation fluid over the range 0.01 to 1.0 μm.
The magnitude of the contracture to phentolamine of ilea incubated with clonidine (1.0 μm) (withdrawal contracture) was directly related to the challenge dose of phentolamine over the range 0.3tol.0μM.
Yohimbine (1.0 μm) or piperoxane (1.0 μm) elicited a response comparable to that elicited by phentolamine but propranolol (1.0 μm) was inactive.
Addition of phentolamine (1.0 μm) to clonidine (1.0 μm) in the incubation fluid abolished the increased response of the preparation to subsequent challenge with phentolamine. 6 Addition of hyoscine (0.5 μm) immediately after challenge with phentolamine restored the tension of the withdrawal contracture to its resting level.
Tetrodotoxin (3.0 μm) given before challenge, prevented phentolamine from eliciting a withdrawal contracture. 8 Ileal segments incubated with clonidine (1.0 μm) were unresponsive to challenge with naloxone (100 nM); and segments incubated with normorphine (1.0 μm) were unresponsive to phentolamine (1.0 μm), although responsive to naloxone.
Normorphine (1.0 μm) restored to resting level the tension of the clonidine withdrawal contracture; and clonidine (0.1 μm) restored to resting level the tension of the contracture to naloxone in ileal segments incubated with normorphine.
These experiments indicate that incubation with clonidine induces, in the final cholinergic motor neurones of the myenteric plexus of the isolated ileum, a dependence the withdrawal from which is expressed as a contracture in response to α‐adrenoceptor antagonists.
Although opiate receptors are not involved in clonidine dependence nor α‐adrenoceptors in opiate dependence, the findings that normorphine suppresses the clonidine withdrawal‐contracture and that clonidine suppresses the contracture of opiate‐dependent ileum to naloxone, suggest that the withdrawal effect studied in both clonidine and normorphine dependence in this preparation is mediated by release of acetylcholine from the final motor neurone.
THE EFFECTS OF SUBSTANCE P AND RELATED PEPTIDES ON α‐AMYLASE RELEASE FROM RAT PAROTID GLAND SLICES
Authors: BROWN C.L. , HANLEY M.R. 
Published: July 2012

The effects of substance P and related peptides on amylase release from rat parotid gland slices have been investigated.
Supramaximal concentrations (1 μ) of substance P caused enhancement of amylase release over the basal level within 1 min; this lasted for at least 40 min at 30°C.
Substance P‐stimulated amylase release was partially dependent on extracellular calcium and could be inhibited by 50% upon removal of extracellular calcium.
Substance P stimulated amylase release in a dose‐dependent manner with an ED50 of 18 nM.
All C‐terminal fragments of substance P were less potent than substance P in stimulating amylase release. The C‐terminal hexapeptide of substance P was the minimum structure for potent activity in this system, having 1/3 to 1/8 the potency of substance P. There was a dramatic drop in potency for the C‐terminal pentapeptide of substance P or substance P free acid. Physalaemin was more potent than substance P (ED50 = 7 nM), eledoisin was about equipotent with substance P (ED50 = 17 nM), and kassinin less potent than substance P (ED50 = 150 nM).
The structure‐activity profile observed is very similar to that for stimulation of salivation in vivo, indicating that the same receptors are involved in mediating these responses.
All the fragments of substance P tested were capable of eliciting a full amylase release response. This indicates that the apparent partial agonist action of the C‐terminal nonapeptide fragment on in vivo salivation is not explicable at the receptor level.
CONVULSANT AND POSSIBLE ANTICHOLINERGIC ACTIONS OF DENDROTOXIN IN THE AMPHIBIAN SPINAL CORD
Authors: COLLIER B. , PADJEN A.L. , QUIK M. , SMITH P.A. 
Published: July 2012

Dendrotoxin (DTOX)6, 6a and 5,6‐1, fractions of the venom isolated from the green mamba (Dendroaspis viridis) promoted both spontaneous and stimulus‐coupled rhythmic activity and antagonized the cholinergically mediated ventral root‐dorsal root potential (VR‐DRP) of frog spinal cord. The different time course and reversibility of these two effects indicates that the toxin has two entirely separate sites of action on the frog spinal cord.
Since DTOX 6 neither blocked nor enhanced responses of ventral and dorsal roots to glutamate, γ‐aminobutyric acid (GABA), β‐alanine, glycine or aspartate, it is unlikely that its convulsant action resulted from an alteration of the postsynaptic actions of inhibitory or excitatory amino acids.
An alteration in the threshold for action potential generation could perhaps contribute to the convulsant action of DTOX 6, although other mechanisms such as blockade of the release of unspecified inhibitory substances cannot be excluded.
In addition to the lack of effect on amino acid responses, DTOX failed to block the polysynaptic DR‐VRP or DR‐DRP pathways, which are mediated at least in part by amino acid neurotransmitters. Although this would be consistent with a specific action of DTOX at the cholinergic synapse of the VR‐DRP pathway, this site of action has not yet been demonstrated unequivocally. Other possible mechanisms whereby DTOX could block VR‐DRP are discussed.
ANTIBIOTIC‐ASSOCIATED COLITIS: AN in vitro INVESTIGATION OF THE EFFECTS OF ANTIBIOTICS ON INTESTINAL MOTILITY
Authors: LEES G.M. , PERCY W.H. 
Published: July 2012

Nine antibiotic compounds in common use were studied to determine their ability to affect intestinal motility in vitro, in the guinea‐pig ileum and rabbit colon.
Ampicillin, doxycycline, mecillinam and metronidazole were without effect over a concentration range which included typical serum levels found when these drugs are used therapeutically.
Clindamycin, gentamicin, kanamycin, pivmecillinam and trimethoprim were all found to inhibit evoked and reflex responses of the guinea‐pig ileum but only clindamycin and trimethoprim also affected evoked responses of the rabbit colon.
Kanamycin and gentamicin appeared to have a predominantly prejunctional action, pivmecillinam and trimethoprim a predominantly post‐junctional action. Clindamycin had a prejunctional action at low concentrations and long exposure times, and a post‐junctional action at high concentrations and short exposure times.
The concentration of each antibiotic required to inhibit the peristaltic reflex of the guinea‐pig ileum was less than that required to inhibit its responses to electrical stimulation or exogenous acetylcholine or histamine but greater than the serum levels associated with their respective use in therapeutic doses.
A sequence of events whereby antibiotic‐induced alterations in gastro‐intestinal motility could lead to the development of pseudomembranous colitis is proposed.
DOES CYCLIC 3′,5′‐ADENOSINE MONOPHOSPHATE ACT AS SECOND MESSENGER IN A VOLTAGE‐DEPENDENT RESPONSE TO 5‐HYDROXYTRYPTAMINE IN Aplysia?
Authors: PELLMAR TERRY C. 
Published: July 2012

The possibility that cyclic adenosine 3′,5′‐monophosphate (cyclic AMP) mediates a voltage‐dependent inward current elicited by 5‐hydroxytryptamine (5‐HT) in RB and LB cells of the abdominal ganglion of Aplysia was tested.
Intracellular injection of cyclic AMP elicited an inward current with a similar time course, potential dependence and ionic sensitivity as the response to 5‐HT.
Intracellular injection of guanylyl imidodiphosphate (GMP‐PNP), which activates adenylate cyclase, neither mimicked nor enhanced the 5‐HT‐evoked current. On the contrary, it reduced the current.
The phosphodiesterase inhibitors, Ro20–1724, isobutyl methylxanthine (IBMX) and theophylline, each antagonized the voltage‐dependent response to 5‐HT. To varying degrees they each induced an inward current.
The adenylate cyclase antagonist, dithiobisnitrobenzoic acic (DTNB), had no effect on the response to 5‐HT when applied either intracellularly or extracellularly. Intracellular injection of the phosphodiesterase activator imidazole also had no effect.
Tubocurarine and neostigmine did not reduce the voltage‐dependent inward current evoked by 5‐HT; methysergide elicited an inward current.
Although the observation that cyclic AMP and 5‐HT can evoke similar voltage‐dependent inward currents in RB and LB neurones of Aplysia might suggest a second messenger role for the cyclic nucleotide, the pharmacological data are inconsistent with this hypothesis.
THE BINDING OF [3H]‐PROSTACYCLIN TO MEMBRANES OF A NEURONAL SOMATIC HYBRID
Authors: BLAIR I.A. , MACDERMOT J. 
Published: July 2012

[3H]‐prostacylin bound to a washed membrane preparation of the NCB‐20 neuronal hybrid cell line.
Kinetic analysis of [3H]‐prostacyclin binding suggested a simple, non‐cooperative bimolecular interaction between the ligand and a single receptor population. The equilibrium dissociation constant was 16.6 nm, and binding at a saturating [3H]‐prostacyclin concentration enabled the receptor density of 2.57 × 105 receptor molecules per cell to be calculated.
At 20°C the rate constant for the forward reaction (k+1) was 2.26 × 105 m−1 s−1, and the rate constant for the dissociation of the ligand‐receptor complex (k‐1) was 3.85 × 10−3 s−1. Thus the dissociation constant (k‐1/k+1) was 17.0 nm.
Prostaglandin E1 and prostacyclin compete for a single receptor in these cells, and comparison of other prostaglandins as inhibitors of [3H]‐prostacyclin binding revealed some of the structural requirements for high‐affinity occupation of prostacyclin receptors.
LEUKOTRIENE B4: A MEDIATOR OF VASCULAR PERMEABILITY
Authors: BRAY M.A. , CUNNINGHAM F.M. , FORD‐HUTCHINSON A.W. , SMITH M.J.H. 
Published: July 2012

Intradermal injection of leukotriene B4 (LTB4) or prostaglandin E2 (PGE2), 1 to 100 ng per skin site produced little or no change in plasma exudation in the rabbit, guinea‐pig and rat.
Intradermal injection of LTB4 together with PGE2 produced a significant increase in plasma exudation in the rabbit, guinea‐pig and rat.
Intradermal injection of LTB4 or PGE2 together with bradykinin (500 ng) resulted in a significant potentiation of the plasma exudation produced by bradykinin alone in the rabbit and guinea‐pig.
LTB4 (1 to 10 ng) had no effect on blood flow in the rabbit skin, in contrast to PGE2 which was a potent vasodilator in this species.
It is concluded that LTB4 is a mediator of vascular permeability and that this effect can only be observed in the presence of a vasodilator such as PGE2.
THE EFFECT OF ANAESTHETICS ON THE UPTAKE AND RELEASE OF γ‐AMINOBUTYRATE AND D‐ASPARTATE IN RAT BRAIN SLICES
Authors: MINCHIN M.C.W. 
Published: July 2012

The effect of various concentrations of thiopentone, pentobarbitone, methohexitone, hydroxydione, alphaxalone/alphadolone, ketamine, α‐chloralose and urethane on the transport of radiolabelled γ‐aminobutyric acid (GABA) and D‐aspartate was investigated.
Uptake of the amino acids was weakly inhibited, if at all, by the anaesthetics and it is unlikely that such effects contribute significantly to their physiological function.
The spontaneous efflux of GABA and D‐aspartate was not detectably altered by any of the drugs tested.
Thiopentone, pentobarbitone, methohexitone and hydroxydione inhibited K+‐stimulated GABA and D‐aspartate release. The other anaesthetics had no effect on K+‐stimulated amino acid release.
The rank order of potency of the inhibitors of K+‐stimulated amino acid release did not correlate with their anaesthetic potency. Furthermore not all inhibitors appeared to be very effective at anaesthetic concentrations.
It is concluded that although it is possible that inhibition of excitatory transmitter release may be involved in the anaesthetic action of some anaesthetics, for many of the substances tested in this study such a mechanism does not appear to be implicated.
CHOLINE ACETYLTRANSFERASE ACTIVITY IN THE SYMPATHETIC NERVES OF THE RABBIT EAR ARTERY
Authors: FLORENCE VERENA M. , HUME W.R. , MATSUNAGA MARSHA L. 
Published: July 2012

No statistically significant difference in the activity of choline acetyltransferase (ChAT) was detected between sympathetically denervated and control rabbit ear artery (REA) tissue. This was interpreted as evidence against the hypothesis that endogenous acetylcholine plays an obligatory role in sympathetic postganglionic neurotransmission.
The values obtained for ChAT activity in the extraneuronal REA tissue were very low, but were greater than the boiled blank values.
Treatment with a specific inhibitor of ChAT did not reduce the REA values, while it did for rabbit iris. Addition of acetylcholinesterase to the REA assay reduced the activity of the collectable product to a markedly lesser degree than was observed with other tissues.
The specificity of the enzyme assay at the very low yield levels observed in the extraneuronal REA tissue was therefore questioned.
THE ROLE OF THE LOCAL ANAESTHETIC PROPERTIES OF β‐ADRENOCEPTOR BLOCKING AGENTS IN ANTAGONIZING CaCl2‐INDUCED ARRHYTHMIAS IN THE RAT
Authors: EVANGELISTA S. , MAGGI C.A. , MELI A. 
Published: July 2012

Eight β‐adrenoceptor blocking agents were compared for their ability to antagonize arrhythmias induced by bolus injections of CaCl2 in rats.
Only those β‐blockers possessing local anaesthetic properties were effective in antagonizing this type of arrhythmia and there was a highly significant correlation between antiarrhythmic and local anaesthetic properties.
Effects on adrenoceptors seem to play only a minor role in the genesis of this type of arrhythmia.
DUAL EFFECTS OF CATECHOLAMINES ON PRE‐ AND POST‐JUNCTIONAL MEMBRANES IN THE DOG TRACHEA
Authors: ITO YUSHI , TAJIMA KIKUO 
Published: July 2012

Effects of noradrenaline or isoprenaline on the membrane and contractile properties of the smooth muscle cell, or on the excitatory neuro‐effector transmission in the dog trachea, in vitro, were observed by use of microelectrodes and double sucrose gap methods.
Noradrenaline (<5 × 10−6 m) or isoprenaline (< 5 × 10−7 m) modified neither the membrane potential nor the membrane resistance. Increased concentrations of noradrenaline (> 5 × 10−5 m) depolarized and isoprenaline (> 5 × 10−7 m) hyperpolarized the membrane, and these actions were suppressed by phentolamine and propranolol respectively. Both catecholamines reduced the membrane resistance.
Noradrenaline (5 × 10−6 m) or isoprenaline (5 × 10−7 m) reduced the resting tension, raised the mechanical threshold required to produce the contraction and suppressed the amplitude of phasic contractions evoked by electrical depolarization of the membrane.
The action potential evoked by an outward current pulse in the presence of tetraethylammonium (TEA) was not affected by 5 × 10−6m isoprenaline, while the mechanical response was markedly suppressed.
The excitatory junction potential (e.j.p.) evoked by electrical field stimulation was blocked by atropine. Noradrenaline (5 × 10−7 m) or isoprenaline (5 × 10−8 m) suppressed the amplitude of e.j.p. with no change in the membrane potential or input membrane resistance. Depression in the amplitude of e.j.ps produced by noradrenaline or isoprenaline reduced the amplitude of phasic contractions evoked by e.j.ps.
These inhibitory actions of the catecholamines on mechanical responses and on e.j.ps were suppressed by pretreatment with propranolol (4 × 10−6 m).
Dog tracheal smooth muscles are innervated by cholinergic excitatory and adrenergic inhibitory systems. Electrical field stimulation produced excitation of both cholinergic and adrenergic nerve fibres, and propranolol (4 × 10−6 m) enhanced the amplitude of e.j.p. generated by excitation of cholinergic nerves when repetitive stimulation (10 stimuli at 20 Hz) was used, but not the amplitude of the e.j.p. evoked by a single stimulus.
5‐Hydroxytryptamine (6 × 10−6 m) produced a tonic contracture of the dog trachea. After pretreatment with atropine (4 × 10−6 m), field stimulation (50 μs in duration and repetitive stimuli at 20 Hz) induced reversal of the contracture induced by 5‐hydroxytryptamine and this was abolished by propranolol (5 × 10−6 m).
These results indicate that endogenous or exogenous catecholamines, in relatively low concentrations, predominantly activate β‐adrenoceptors in the pre‐ and post‐junctional membrane in the dog trachea, and induce muscle relaxation.
ROLE OF CENTRAL β‐ADRENOCEPTORS IN THE CONTROL OF PENTYLENETETRAZOL‐INDUCED CONVULSIONS IN RATS
Authors: LOUIS W.J. , PAPANICOLAOU JENNY , SUMMERS R.J. , VAJDA F.J.E. 
Published: July 2012

The role of central β‐adrenoceptors in the anticonvulsant effect of β‐adrenoceptor antagonists has been examined.
Oral administration of (−)‐and (+)‐propranolol (0.05–1 mg/kg) and (±)‐pindolol (0.025–0.5 mg/kg) produced a dose‐dependent decrease in duration of convulsions produced by pentylenetetrazol (PTZ 50 mg/kg, i.p.) in rats.
At the EC5+ level, (−)‐propranolol is seven times more effective than the (+)‐isomer.
Oral administration of (−)‐, (+)‐or (±)‐practolol (1–10 mg/kg) or (−)‐or (+)‐timolol (1–10 mg/kg), two β‐adrenoceptor antagonists that do not penetrate the blood brain barrier, had no significant effect on the duration of PTZ‐induced convulsions.
Intracerebroventricular administration of (−)‐propranolol (0.5 μg/kg) or (−)‐timolol (0.25 μg/kg) produced highly significant anticonvulsant effects whereas the (+)‐isomers at the same dose level were ineffective. (±)‐Pindolol (0.25 μg/kg) was also much more effective given by this route than when given orally. The (+)‐and (−)‐isomers of the β1‐adrenoceptor selective antagonist practolol (10 μg/kg) exerted only weak anticonvulsant effects.
This study provides evidence that β‐adrenoceptor antagonists exert an anticonvulsant effect through central β2‐adrenoceptors. At high dose levels, additional anticonvulsant activity is associated with membrane stabilization in those antagonists which possess this property.
EFFECTS OF CHLORPROMAZINE ON THE ELECTRICAL AND MECHANICAL PROPERTIES OF INTACT AND SKINNED MUSCLE CELLS OF GUINEA‐PIG MESENTERIC ARTERY
Authors: ITOH TAKEO , KURIYAMA HIROSI , SUZUKI HIKARU 
Published: July 2012

Effects of chlorpromazine on the contraction evoked in intact muscles, and of chlorpromazine or calmodulin on the contraction evoked in the saponin‐treated skinned muscles of the guinea‐pig mesenteric artery were investigated.
Chlorpromazine, above 5 × 10−7 m, depolarized the membrane and reduced the membrane resistance measured from the current‐voltage relationships at the depolarized and resting membrane potential levels.
The contraction evoked by excess [K]o, NaCl‐free Krebs and by caffeine was suppressed by application of chlorpromazine; contractions induced by the former two treatments were suppressed to a greater extent than those induced by the latter. Contractions induced by excess [K]o or NaCl‐free Krebs ceased in Ca‐free solution, but not those induced by caffeine, i.e. influxes of Ca across the membrane were more suppressed than was the release of Ca from the storage sites by chlorpromazine.
In skinned muscles, chlorpromazine suppressed and calmodulin enhanced the Ca‐induced contraction in a dose‐dependent fashion. The minimum concentration of chlorpromazine required to suppress the Ca‐induced contraction (10−5 m) was 10−6 m and that of calmodulin to enhance the Ca‐induced contraction was 10−7m.
After skinned muscles had been loaded with Ca, chlorpromazine or calmodulin itself did not induce the contraction by the release of stored Ca in the cell. However, calmodulin increased and chlorpromazine suppressed the accumulation of Ca into the storage site (presumably sarcoplasmic reticulum).
From the present results, it is suggested that chlorpromazine acts on the surface membrane and suppresses Ca‐influx, thus causing a relaxation of the mesenteric artery. However, when chlorpromazine or calmodulin was applied to skinned muscles, the former suppresses and the latter enhances the Ca accumulation into the storage site and the activation of contractile proteins. Thus chlorpromazine causes the relaxation of the vascular tissue. However, a lower concentration of chlorpromazine was required to suppress the Ca influx than to suppress the Ca accumulation into the storage site or the activity of calmodulin in contractile protein. Thus vasodilatation induced by chlorpromazine in vitro, is mainly due to the suppression of Ca influx.
IS RECEPTOR ACTIVATION INVOLVED IN THE MECHANISM BY WHICH (+)‐FENFLURAMINE AND (+)‐NORFENFLURAMINE DEPLETE 5‐HYDROXYTRYPTAMINE IN THE RAT BRAIN?
Authors: INVERNIZZI R. , KMIECIAK‐KOLADA K. , SAMANIN R. 
Published: July 2012

The effects of (+)‐fenfluramine, (+)‐norfenfluramine and reserpine on the concentrations of 5‐hydroxytryptamine (5‐HT) and 5‐hydroxyindoleacetic acid (5‐HIAA) in brainstem and telencephalon were studied in rats treated with methergoline, a 5‐HT antagonist.
Methergoline significantly reduced the effect of (+)‐norfenfluramine (5 mg/kg) on 5‐HT levels in telencephalon and brainstem but did not modify the effect of (+)‐norfenfluramine (2.5 mg/kg).
Neither the effect of (+)‐fenfluramine on 5‐HT levels nor the decrease of 5‐HT metabolism caused by (+)‐fenfluramine and (+)‐norfenfluramine was significantly modified by methergoline treatment.
Methergoline potentiated the effects of reserpine on brain indoles. The effect was particularly evident on 5‐HIAA levels in the brainstem, although significant effects were found on 5‐HT in the brainstem and 5‐HIAA in the telencephalon depending on the dose of reserpine used.
The results show that postsynaptic receptor activation may partially contribute to the depletion of brain 5‐HT caused by (+)‐norfenfluramine in the rat. This mechanism does not seem to play a significant role in the effect of (+)‐fenfluramine.
MECHANISM OF CADMIUM‐INDUCED CONTRACTION IN ILEAL LONGITUDINAL MUSCLE OF GUINEA‐PIG
Authors: ASAI FUMITOSHI , NISHIMURA MASAKAZU , SATOH EIKI , URAKAWA NORIMOTO 
Published: July 2012

The mechanism of cadmium (Cd2+)‐induced contraction was studied in isolated ileal longitudinal muscle of guinea‐pig.
CdCl2 (1 × 10−8 to 1 × 10−4 m) caused a transient contraction which subsided within approximately 6 min of application. The contraction was reproducible and dependent on the concentration. The dose‐response curve was bell‐shaped. A maximal response was observed at concentrations of 5 × 10−6 to 1 × 10−5 m.
The contractile effect was inhibited to some degree at 20°C or by tetrodotoxin (0.1 μg/ml), hyoscine (0.1 μg/ml) or hexamethonium (10 μg/ml), but completely inhibited by Ca2+‐removal from the medium.
Cd2+ increased the output of [14C]‐acetylcholine biosynthesized from [14C]‐choline by the preparation depending on the concentration. The increase terminated within the first 6 min and was reduced by tetrodotoxin (0.1 μg/ml) or by removal of Ca2+ from the medium.
Both the contractile and transmitter releasing effects of Cd2+ were dependent on the concentration of external Ca2+. Strontium ions were able to replace Ca2+ for Cd2+‐induced transmitter release.
It is suggested that Cd2+ contracts ileal longitudinal muscle through a release of cholinergic transmitter from the parasympathetic nerve terminals, which is dependent on external Ca2+. It also has a smaller hyoscine‐resistant contractile effect, presumably due to a direct action on smooth muscle cells.