bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dendrobine, an antagonist of β‐alanine, taurine and of presynaptic inhibition in the frog spinal cord
Authors: Kudo Yoshihisa , Tanaka Atsuko , Yamada Kiyoyuki 
Published: July 2012

The effects of dendrobine and nobiline, alkaloids isolated from Dendrobium nobile, on the electrical activity and on amino acid‐induced depolarizations of primary afferent terminals were tested on the frog isolated spinal cord and were compared with those of picrotoxinin and strychnine.
Dendrobine (3 × 10−5 m) caused a slight hyperpolarization in both dorsal and ventral roots and this hyperpolarization was accompanied by the augmentation of the dorsal root potential (DR‐DRP) and the ventral root potential and reflex (DR‐VRP and DR‐VRR). The amplitude of the dorsal root reflex (DR‐DRR) however, was reduced significantly. Nobiline (3 × 10−5 m) had no significant effect on either the root potentials or the reflexes.
Dendrobine (3 × 10−5 m) reduced the dorsal root potential induced by repetitive antidromic stimulation of ventral root (VR‐DRP) as well as diminishing the maximum rate of rise of the dorsal root potential induced by the stimulation of adjacent dorsal roots (DR‐DRP), during which time the amplitude of the DR‐DRP was seen to be augmented.
Dendrobine (3 × 10−5 m) reduced the β‐alanine‐ and taurine‐induced depolarizations of primary afferent terminals, while having little effect upon GABA‐ and glycine‐induced depolarizations.
Dendrobine (10−5 m) reversibly blocked the presynaptic inhibition caused by antidromic conditioning stimulation of the ventral root.
These effects of dendrobine were qualitatively similar to those of strychnine but were somewhat different from those of picrotoxinin, a molecule having the same picrotoxane skeleton.
The present results are discussed with reference to the likely neurotransmitters involved in presynaptic inhibition in the frog spinal cord, and with respect to the structure‐activity relationship of picrotoxane compounds as amino acid antagonists.
Accelerating effects of pentobarbitone on the inactivation process of the calcium current in Helix neurones
Authors: Nishi K. , Oyama Y. 
Published: July 2012

The effect of pentobarbitone on Ca2+ current (ICa), separated from other ionic currents was studied under voltage clamp using a suction pipette technique in Helix neurones.
Pentobarbitone depressed the maximal peak amplitude (MPA) of ICa in a concentration‐dependent manner without shifting the current‐voltage (I‐V) relationships along the voltage axis. Increases in external Ca2+‐concentration ([Ca2+]***o) overcame the inhibitory action of the agent on MPA.
Pentobarbitone markedly accelerated the decay phase of ICa which took a distinctly different time course from that of the control. The accelerating action of the agent on the decay phase of ICa was not overcome by increases in [Ca2+]o. In the presence of internal EGTA (20 mm), pentobarbitone also accelerated the decay of ICa.
Changes in pH of the external perfusing solution altered the potency of pentobarbitone in depressing MPA; in the presence of pentobarbitone (3 × 10−4 m) at pH of 7.0, 8.0 and 9.0, fractional inhibition was approx. 46%, 21% and 4%, respectively.
Internal application of pentobarbitone (10−4‐10−3 m) inhibited MPA, but exerted no effect on the decay phase of ICa.
Pentobarbitone (10−4 m) markedly accelerated the decrease of MPA of ICa induced by repetitive stimuli applied at an interval of 150 ms, indicating a use‐dependent depression of MPA.
Results provide evidence that pentobarbitone has a dual action on ICa, inhibiting MPA and accelerating the decay phase of ICa.
Actions of isosorbide dinitrate on smooth muscle cells of rabbit vascular tissues
Authors: Ishikawa S. , Ito Y. , Itoh T. , Kanmura Y. , Kuriyama H. , Makita Y. 
Published: July 2012

To investigate the mechanism of the anti‐anginal actions of isosorbide dinitrate (ISDN), the effects of this agent on smooth muscle cells of intact and skinned preparations of the rabbit mesenteric artery and vein, and of the coronary artery were studied.
ISDN (<10−5 m) had no effect on the membrane potential or resistance of smooth muscle cells of the mesenteric artery and vein under resting conditions, nor when the membrane was depolarized by the presence of various concentrations of [K]o or noradrenaline (NA). The amplitude of spike evoked by outward current pulse after pretreatment with 10 mm tetraethylammonium (TEA) in the mesenteric artery was slightly inhibited by application of 10−5 m ISDN.
The K‐induced and NA‐induced contractions in the mesenteric artery were not affected by 10−5 m ISDN, while those evoked in the mesenteric vein were inhibited in concentrations above 10−6m.
The amplitude and facilitation of excitatory junction potentials evoked by perivascular nerve stimulation in the mesenteric artery were not affected by 10−5 m ISDN.
In skinned muscles, the free calcium concentration (pCa)‐tension relationships observed in the mesenteric artery and vein were not affected by 10−5 m ISDN. This agent had no effect on Ca accumulation into and Ca release from the stores in muscle cells of the mesenteric artery and vein, in skinned preparations.
In the rabbit coronary artery, the membrane potential, resistance and spike evoked in the presence of 10 mm TEA were not affected by application of 10−5 m ISDN. The contraction evoked by excess concentrations of [K]o was not affected. The contraction evoked by a low concentration of acetylcholine (3 × 10−7 m) but by high concentrations (> 10−6m) was slightly inhibited by 10−5 m ISDN. A tonic contraction induced in 39 mm [K]o was reduced by 10−5 m nitroglycerine but not by 10−5m ISDN.
Thus in rabbit vascular tissues, ISDN mainly acts on the venous system in vitro. The induced vasodilatation may lead to a reduction in the venous return and hence, reduce oxygen consumption in the cardiac muscles. This effect of ISDN may relate to the anti‐anginal actions.
Electrophysiological studies of some semisynthetic cardiac glycoside derivatives in isolated papillary muscle of the guinea‐pig
Authors: Lüllmann H. , Niehus U. , Pulss W. , Ravens Ursula 
Published: July 2012

The effects of digitoxin, 3α‐methyl‐digitoxigenin‐3β‐monoglucoside (3α‐MDM), 3α‐methyl‐digitoxigenin (3α‐MD), proscillaridin, 4, 5‐methylene‐procillaridin (4, 5‐MP), and 3β‐hydroxy‐4, 5‐methylene‐A, B‐trans‐scillarenin (3β‐HMTS) on force of contraction and on the transmembrane action potentials were examined in isolated papillary muscles of guinea‐pigs.
All derivatives exhibited the typical cardiac glycoside effects: i.e. they increased the force of contraction and shortened the action potential duration at 20% (plateau phase) and 90% of repolarization. With digitoxin, 3β‐HMTS and 4, 5‐MP a transient prolongation in action potential duration was observed at the lower concentrations. The action potential amplitude and the resting membrane potential were reduced consistently only with the higher concentrations used.
The onset of the positive inotropic effects of 3α‐MDM, 3α‐MD and 3β‐HMTS was more rapid than that of digitoxin and proscillaridin. The increment in contractile force reached a maximum well before the full shortening effect on the action potential duration had developed. The shortening of the action potential is thought to be responsible for the biphasic nature of the positive inotropic effect.
With 3α‐MD and 3α‐MDM even toxic effects, e.g. increase in baseline tension, were completely reversible after washing in drug‐free solution.
The dose‐response curves for the positive inotropism can only be compared reliably once the equilibrium of drug action has been established. This steady state is probably reflected by the development of the full shortening in action potential duration.
Depolarizing responses to glycine, β‐alanine and muscimol in isolated optic nerve and cuneate nucleus
Authors: Simmonds M.A. 
Published: July 2012

Concentration‐dependent depolarizations were evoked by glycine and β‐alanine 5 × 10−4‐10−2m and by the γ‐aminobutyric acid (GABA) analogue, muscimol 10−6‐10−4m.
The maximal response to glycine was several‐fold higher than that to muscimol on optic nerve but the reverse was found on the dorsal funiculus fibres in the cuneate nucleus, β‐Alanine evoked a similar maximal response to glycine on optic nerve but a considerably higher maximum than glycine in the cuneate nucleus.
Strychnine was 19.5 times more potent as a glycine antagonist (pA2 = 6.58) than as a muscimol antagonist. Bicuculline was 156 times more potent as a muscimol antagonist than as a glycine antagonist. Other antagonists of muscimol, i.e. tubocurarine, Picrotoxin and leptazol, and potentiators of muscimol, i.e. pentobarbitone and flurazepam, had little or no effect on responses to glycine.
Responses to β‐alanine had pharmacological properties compatible with a mixed action on both GABA and glycine receptors.
The rat isolated optic nerve appears to be a useful preparation for studying the pharmacology of the neuronal glycine receptor plus chloride ionophore complex.
The relative significance of spinal and supraspinal actions in the antinociceptive effect of morphine in the dorsal horn: an evaluation of the microinjection technique
Authors: Clark S.L. , Edeson R.O. , Ryall R.W. 
Published: July 2012

Large quantities of morphine injected directly into the brainstem of spinal anaesthetized cats inhibited the noxious heat‐evoked excitation of dorsal horn neurones. The amounts required were similar to those that were required intravenously in cats with the spinal cord intact or transected.
When the spinal cord was intact the amount of morphine microinjected into the brainstem required to inhibit the excitation of dorsal horn neurones was about ten fold less than it was in spinal animals.
It is concluded that large, but not small doses of morphine microinjected into the brainstem can exert effects on the spinal cord after first entering the circulation. The effects of small doses are attributed to a local action in the brainstem which causes inhibition of spinal neurones either by activating descending inhibitory neuronal systems or by liberating endogenous substances which reach the spinal cord via the cerebro‐spinal fluid.
The concentrations of morphine achieved at various distances from the site of injection by the microinjection of μg quantities and the time courses of the concentration changes were calculated from diffusion equations, assuming diffusion coefficients of 3 or 5 × 106 cm2 s−1. The curves obtained closely approximated those obtained experimentally.
The concentrations achieved at distances up to 2 mm from the site of injection of 10 μg of morphine were calculated to exceed 10−4m and the time‐courses of these concentration changes were compatible with the time course of inhibition of spinal neurones, or the production of analgesia after microinjection. Such concentrations are vastly in excess of those achieved in the brain after the systemic administration of morphine in analgesic doses.
It is concluded that the local effects in the brainstem produced by the microinjection of pig quantities of morphine have no relevance to the mechanism of analgesia produced by systemic administration.
Effects of ovarian steroids upon responses mediated by adrenoceptors in separated layers of the myometrium and in the costo‐uterine muscle of the guinea‐pig
Authors: Hartley Margaret L. , Pennefather Jocelyn N. , Story Margot E. 
Published: July 2012

This study describes the effects of ovarian steroid hormones upon the responses to adrenoceptor agonists of isolated myometrium, separated into its longitudinal and circular layers, and of costo‐uterine muscle from guinea‐pigs. The preparations were field‐stimulated at 100 s intervals, and the adrenoceptor agonists phenylephrine and isoprenaline produced enhancement or inhibition of the evoked contractions.
Isoprenaline produced propranolol‐sensitive inhibitory effects in longitudinal and circular myometrium and costo‐uterine muscle preparations from animals from all experimental groups: i.e. from nonsteroid‐treated animals (ovariectomized and intact); intact animals treated with either oestrogen or progesterone alone; ovariectomized animals treated with oestrogen; ovariectomized and intact animals treated with progesterone following oestrogen priming; and from animals 1–4 days post‐partum. Longitudinal myometrial preparations from progesterone‐treated oestrogen‐primed and from post‐partum animals were most sensitive to this agonist.
Phenylephrine produced phentolamine‐sensitive excitatory effects in circular myometrial and costo‐uterine muscle preparations from animals from all the experimental groups. In contrast, propranolol‐sensitive inhibitory responses to phenylephrine occurred in longitudinal myometrial preparations taken from animals treated with progesterone following oestrogen priming, and from post‐partum animals. Longitudinal myometrium from animals from the remaining experimental groups exhibited phentolamine‐sensitive excitatory responses to phenylephrine.
The basis for the selective effect upon the longitudinal myometrium of exposure to progesterone following a period of oestrogen priming, is discussed. The results described are consistent with the possibility that in the longitudinal layer of guinea‐pig uterus exposed to progesterone following oestrogen priming there is an increase in the proportion of β‐adrenoceptors in this layer. This increase may reduce the likelihood of contractions arising via direct stimulation of α‐adrenoceptors in this layer in response to sympathetic activation during pregnancy.
Prostaglandin synthesis inhibitors: effect on angiotensin II‐ and oxytocin‐induced contractions in rat uterine smooth muscle
Authors: Hall M.M. 
Published: July 2012

Eicosatetraynoic acid, the acetylene analogue of arachidonic acid, which inhibits both the cyclo‐oxygenase and lipoxygenase pathways, reduced the contractile response of rat uterine smooth muscle to either angiotensin II or oxytocin.
Indomethacin, an inhibitor of cyclo‐oxygenase, did not reduce the response to angiotensin II but did abolish the contractile response to low doses of oxytocin.
Nordihydroguaiaretic acid, a lipoxygenase inhibitor, totally abolished the uterine response to either oxytocin or angiotensin II.
The contractile response to carbachol, a cholinoceptor agonist, was unaffected by pretreatment with any of the cyclo‐oxygenase or lipoxygenase inhibitors.
From these findings, it can be implied that some product of the arachidonate lipoxygenase pathway augments peptide‐induced contractions of the rat uterus.
Calcium antagonists: effects on cerebral blood flow and blood‐brain barrier permeability in the rat
Authors: Edvinsson L. , Johansson B.B. , Larsson B. , MacKenzie E.T. , Skärby T. , Young A.R. 
Published: July 2012

Because they affect isolated cerebral arteries, some calcium antagonists have been studied on the intact cerebral circulation of the rat.
Global cerebral blood flow (133Xe clearance technique) was measured in anaesthetized rats. Neither perhexiline (0.1 μg/kg to 1.0 mg/kg, i.v.) nor diltiazem (0.06–0.6 mg/kg, i.v.) had any significant effect on resting cerebral blood flow when measured 5 min after each dose. A high dose of nifedipine (1.0 mg/kg, i.v.) was administered during induced hypocapnia. Nifedipine failed to modify the hypocapnic vasoconstriction of the cerebral vasculature when compared to vehicle‐treated rats.
The possibility of discrete changes in regional cerebral blood flow was investigated. Local cerebral blood flow was measured in a number of brain regions by the [14C]‐ethanol technique 15 min after the administration of nifedipine (20 or 100 μg/kg, i.v.). Nifedipine had no apparent effect on regional blood flow in the rat brain.
Acute arterial hypertension increases protein leakage into the brain, a phenomenon susceptible to drugs that act on endothelial pinocytosis which is known to be calcium‐dependent. The increase in protein extravasation, induced by the intravenous administration of either angiotensin II or adrenaline, was unchanged in rats previously treated with either nimodipine (20 μg/kg, i.v.) or nifedipine (50 μg/kg, i.v.) when dissolved in ethanol alone. However, nifedipine (20 μg/kg, i.v.) when dissolved in a solution of polyethylene glycol and ethanol further enhanced the hypertension‐induced increase in brain albumin permeability.
In conclusion, we have been unable to demonstrate any apparent effects of various calcium antagonists on the intact cerebral circulation of the rat, despite the number of different experimental models used.
Formation of 6‐keto prostaglandin E1 in mammalian kidneys
Authors: Griffiths R.J. , Moore P.K. 
Published: July 2012

The metabolism of prostacyclin (PGI2) and 6‐keto prostaglandin F1α (6‐keto PGF1α) was studied in cell‐free homogenates of rat, rabbit and guinea‐pig kidney.
Rabbit kidney converted both PGI2 and 6‐keto PGF1α to a stable metabolite with chromatographic and biological activity identical to that of authentic 6‐keto PGE1. Activity was found in the kidney cortex but not medulla, was inhibited by NAD+ or NADP+ (5 mM) and showed an optimum temperature requirement of 37°C.
Guinea‐pig kidney converted PGI2 but not 6‐keto PGF1α to a labile, biologically active metabolite which was not 6‐keto PGE1.
No conversion of prostacyclin or 6‐keto PGF1α to biologically active metabolites occurred in cell‐free homogenates of rat kidney, liver and colon or guinea‐pig liver and colon.
6‐keto PGE1 rapidly lost spasmogenic activity on the rat stomach strip following incubation with rabbit or guinea‐pig kidney supernatant in the absence of added cofactors. No loss of activity occurred on incubation with rat kidney.
Rutin (50 μM) potently inhibited synthesis of 6‐keto PGE1 from added PGI2 by rabbit kidney cortex. This reaction was potentiated by a similar concentration of sulphasalazine, carbenoxolone, imidazole, papaverine or indomethacin.
The relevance of these findings for the possible physiological and pathological roles of 6‐keto PGE1 in the kidney is discussed.
Direct inhibitory effects of some ‘calcium‐antagonists’ and trifluoperazine on the contractile proteins in smooth muscle
Authors: Spedding M. 
Published: July 2012

Taenia preparations from the guinea‐pig caecum were treated with Triton X‐100 and glycerol to disrupt the plasma membrane. Disruption of the sarcolemma was confirmed by electronmicroscopy. The preparations contracted in response to low concentration of Ca2+ (10–40 μM) and the contractions were dependent upon exogenous adenosine triphosphate (ATP).
Nifedipine (100 μM), verapamil (100 μM) and diltiazem (100 μM) did not inhibit Ca2+‐induced activation of the contractile proteins.
In contrast, fendiline (100 μM), cinnarizine (100 μM), flunarizine (100 μM), pimozide (100 μM) and trifluoperazine (100 μM) significantly inhibited Ca2+‐induced contractions. The effects of cinnarizine (100 μM) were reversible.
These findings disclose further differences between calcium‐antagonists and suggest that certain of these agents have an intracellular site of action.
Evidence that the spasmogenic action of tetraethylammonium in guinea‐pig trachealis is both direct and dependent on the cellular influx of calcium ion
Authors: Foster R.W. , Small R.C. , Weston A.H. 
Published: July 2012

Tetraethylammonium (TEA, 1–8 mmol/l) evoked spasm of guinea‐pig trachealis which was unaffected by atropine (1 μmol/l), mepyramine (1 μmol/l) or tetrodotoxin (3 μmol/l).
The spasm evoked by TEA was markedly suppressed in Ca2+‐free Krebs solution while that evoked by acetylcholine was much less affected.
Extracellular electrical recording showed that exposure to Ca2+‐free Krebs solution suppressed both spontaneous electrical slow wave activity of the trachea and the spasm and slow waves induced by TEA. These effects were reversible.
TEA (2 and 8 mmol/1) increased the lanthanum‐resistant calcium fraction of trachea.
It is concluded that TEA acts directly on the smooth muscle of guinea‐pig trachea, that the spasm and electrical slow waves evoked are Ca2+‐dependent and that the cellular influx of Ca2+ is increased.
Increased inhibitory action against adenosine 5′‐triphosphate in the isolated taenia of the guinea‐pig caecum by substitution in the A‐ring of 2‐phenylisatogen
Authors: Foster H. , Hooper M. , Imam S.H. , Lovett G.S. , Nicholson J. , Swain C.J. , Sweetman A.J. , Weetman D.F. 
Published: July 2012

The ability of a series of 17 isatogen derivatives to relax smooth muscle, inhibit adenosine 5′‐diphosphate (ADP)‐stimulated respiration in isolated mitochondria and to antagonize the inhibitory effects of adenosine 5′‐triphosphate (ATP) on smooth muscle was measured.
Substitution in the 4‐ and 7‐positions of the A‐ring gave compounds that were strong inhibitors of mitochondrial ATP synthesis and potent, non‐specific smooth muscle relaxants. The compounds also possessed ATP‐receptor blocking activity.
Substitution in the 5‐ and 6‐positions of the A‐ring decreased both the relaxant effect on smooth muscle and inhibition of ATP synthesis, whilst enhancing ATP‐receptor antagonism.
In a series of 6‐substituted 2‐phenylisatogens, 6‐methoxy‐2‐phenylisatogen was the most effective ATP‐receptor antagonist. This compound also showed the greatest separation of the desired pharmacological activity (ATP‐receptor blockade) from the other two activities (smooth muscle relaxation and inhibition of mitochondrial ATP synthesis).
The effects of 3,4‐dihydro‐8‐(2‐hydroxy‐3‐isopropylaminopropoxy)‐3‐nitroxy‐2H‐1‐benzopyr an (K‐351) and its denitrated derivative on smooth muscle cells of the dog coronary artery
Authors: Kou K. , Suzuki H. 
Published: July 2012

Effects of 3,4‐dihydro‐8‐(2‐hydroxy‐3‐isopropylaminopropoxy)‐3‐nitroxy‐2H‐1‐benzopyran (K‐351) and its derivative, 3,4‐dihydro‐8‐(2‐hydroxy‐3‐isopropylaminopropoxy)‐3‐hydroxy‐2H‐1‐benzopyran (K‐351 (N‐)) on the electrical and mechanical properties of smooth muscles of the dog coronary and mesenteric arteries were investigated, and the findings were compared with data obtained with nitroglycerine.
In both proximal and distal regions of the coronary arteries, K‐351 and nitroglycerine reduced the resting tone and suppressed the contractions produced by high‐potassium solution or by current passage to the same extent, with no remarkable change in the electrical properties of the smooth muscle membrane.
In the proximal regions of the descending coronary artery, low and high concentrations of noradrenaline (NA) produced relaxation and contraction of the muscle, respectively. In the distal region, NA consistently relaxed the muscle with concentrations up to 10−5M. In both regions, the contraction or relaxation was suppressed by phentolamine or propranolol, respectively.
K‐351 suppressed the NA‐induced contraction. K‐351(N‐) potentiated the NA‐induced contraction and suppressed the relaxation, but these actions were weaker than those of propranolol. Nitroglycerine suppressed the NA‐induced contraction and the potency was weaker than that of K‐351.
In the mesenteric artery, K‐351 depressed excitatory junction potentials, spikes and contractions evoked by perivascular nerve stimulation, while K‐351(N—) potentiated or depressed mechanical responses, with no change in the electrical responses. Nitroglycerine also depressed the mechanical responses evoked by perivascular nerve stimulation with no change in the electrical responses.
These results suggest that K‐351 has a blocking action on postjunctional adrenoceptors, and also dilator actions similar to the actions of nitroglycerine on the dog coronary artery, while K‐351 (N—) possesses a weak β‐adrenoceptor blocking action.