bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of 5‐hydroxytryptamine on [3H]‐acetylcholine release from guinea‐pig striatal slices
Authors: Bianchi Clementina , Siniscalchi Anna , Beani Lorenzo 
Published: July 2012

The effect of 5‐hydroxytryptamine (5‐HT) on spontaneous and electrically‐evoked tritium efflux was studied in guinea‐pig caudate nucleus slices preloaded with [3H]‐choline.
5‐HT, 10–300 μmol1−1, temporarily increased the spontaneous tritium efflux (as well as the endogenous acetylcholine (ACh) release) and, after 15 min perfusion, inhibited it. The facilitatory effect of 5‐HT on spontaneous efflux was increased while the inhibitory effect did not occur in slices taken from dopamine‐depleted guinea‐pigs.
The increase in spontaneous tritium efflux by 5‐HT was blocked by methiothepin, methysergide (pA2 8.7) and by the selective 5‐HT2 antagonist, ritanserin (pA2 6.7).
The inhibition of spontaneous tritium efflux by 5‐HT was prevented by methysergide and methiothepin but not by ritanserin and (−)‐propranolol.
5‐HT, 100 μmol1−1, inhibited the electrically‐evoked tritium efflux and this effect was unchanged in dopamine‐depleted slices.
The inhibition of electrically‐evoked tritium efflux by 5‐HT was blocked by methiothepin and methysergide but not by (−)‐propranolol or ritanserin.
These results suggest that 5‐HT may exert a rapid and transient (excitatory) and a more prolonged (inhibitory) control over striatal cholinergic neurones.
A comparison of bradykinin‐ and capsaicin‐induced myocardial and coronary effects in isolated perfused heart of guinea‐pig: involvement of substance P and calcitonin gene‐related peptide release
Authors: Manzini Stefano , Perretti Francesca , de Benedetti Laura , Pradelles Philippe , Maggi Carlo Alberto , Geppetti Pierangelo 
Published: July 2012

Bradykinin and capsaicin were compared for their ability to elicit functional effects and to release sensory neuropeptides from guinea‐pig isolated perfused hearts.
Both bradykinin (10 μm) and capsaicin (1 μm) produced a marked increase in coronary flow, a large positive chronotropic effect and a significant reduction in contractile strength. These actions were associated with a marked release of substance P‐like immunoreactivity (SP‐LI) and calcitonin gene‐related‐like immunoreactivity (CGRP‐LI). The percentage of the tissue content of SP‐LI and CGRP‐LI released by each agent was similar, although bradykinin was less effective than capsaicin. The ratio of SP‐LI/CGRP‐LI released by both agents was similar to that present in cardiac tissue.
Neuropeptide release could be evoked only once with capsaicin but at least four times with bradykinin. Also, functional responses to capsaicin underwent desensitization. After either in vitro or systemic capsaicin pretreatment, the release of SP‐LI and CGRP‐LI by bradykinin was reduced and the positive chronotropic effect of bradykinin was significantly reduced, while the increase in coronary flow and negative inotropic responses remained unchanged.
Pretreatment with indomethacin (10 μm) strongly antagonized the release of SP‐LI and CGRP‐LI by bradykinin and reduced the increase in heart rate.
These findings suggest that activation by bradykinin (probably through indirect mechanisms) of capsaicin‐sensitive sensory nerves in the heart, leads to a local release of sensory neuropeptides. These neuropeptides, in turn, could participate in determining the complex functional effects of this kinin on cardiac performance.
What confers specificity on glycine for its receptor site?
Authors: Tokutomi Naofumi , Kaneda Makoto , Akaike Norio 
Published: July 2012

The structural requirements for activation of the glycine receptor were studied in isolated ventromedial hypothalamic neurones of rats by use of a ‘concentration‐clamp’ technique under single‐electrode voltage‐clamp conditions.
α‐Amino acids (l‐α‐alanine, and d‐α‐alanine, and l‐serine), and glycine‐methylester, glycine‐ethylester and β‐amino acids (β‐alanine and taurine) produced a transient inward Cl− current, which was similar to that induced by glycine.
The responses to individual α‐ and β‐amino acids were selectively antagonized by strychnine, but were not affected by bicuculline, picrotoxin or the taurine antagonist, TAG (6‐aminomethyl‐3‐methyl‐4H,1,2,4‐benzothiadiazine‐1,1‐dioxide hydrochloride), suggesting that α‐ and β‐amino acids activate the same glycine receptor.
β‐Amino acids were slightly more potent than the α‐amino acids in causing cross‐desensitization of the glycine response.
From the results of the structure‐activity analysis of the optical isomers of α‐alanine, serine and cysteine, a tentative structure of the glycine receptor is proposed.
Heterogeneity of nucleoside transport inhibitory sites in heart: a quantitative autoradiographical analysis
Authors: Parkinson Fiona E. , Clanachan Alexander S. 
Published: July 2012

The distribution of nucleoside transport inhibitory sites in rat and guinea‐pig cardiac sections was investigated by use of [3H]‐nitrobenzylthioinosine ([3H]‐NBMPR) autoradiography. The distribution of these sites was heterogeneous in guinea‐pig sections and homogeneous in rat sections.
The areas of high density of nucleoside transport inhibitory sites found in guinea‐pig cardiac sections were compared to the distribution of an endothelial cell marker, von Willebrand Factor, determined by radioimmunocytochemistry. These two markers were co‐localized suggesting that coronary endothelial cells from guinea‐pig have a high density of NBMPR binding sites and thus may have a high nucleoside transport capacity.
Nucleoside transporter subtypes with differing affinity for NBMPR or dipyridamole were investigated by quantitative autoradiography. Sites in rat tissues had high affinity for NBMPR (KD = 0.6 nm) but were of low sensitivity to dipyridamole (Ki = 3.1 μm). In guinea‐pig sections, areas of high and low [3H]‐NBMPR binding site density were analyzed separately. In both areas, sites had high affinity for NBMPR (KD = 1.4 nm, 4.5 nm, respectively) and dipyridamole (Ki = 108 nm, 245 nm, respectively).
While differences in density of nucleoside transport inhibitory sites are detectable between distinct regions of the heart, subtypes differing in affinity for NBMPR or dipyridamole were not evident. Therefore, more detailed structure activity studies are required to determine if subtypes of these sites exist within a single heart.
Inotropic and chronotropic effects of N6‐substituted derivatives of cyclic AMP as assessed in guinea‐pig isolated right atria and papillary muscle
Authors: Kawada Tomie , Yoshida Yutaka , Imai Shoichi 
Published: July 2012

The inotropic and chronotropic actions of N6‐substituted adenosine 3″:5″‐cyclic monophosphate (cyclic AMP) derivatives (N6‐R cyclic AMPs) were studied in guinea‐pig isolated right atrial preparations and in the papillary muscle preparations from guinea‐pig right ventricle.
All the N6‐R cyclic AMPs except N6‐C14H29 produced positive inotropic effects in papillary muscle. The C5H11, C6H13, C7H15, C8H17 and C9H19 compounds were the most potent as inotropic agents, the potency being lower with compounds having longer or shorter N6‐side chains than these.
In right atria N6‐C2H5‐C7H15 cyclic AMPs produced negative chronotropic effects. However, after treatment of the preparations with 8‐phenyltheophylline the negative chronotropic effects were either much attenuated or abolished, indicating the involvement of adenosine receptors.
All the N6‐R cyclic AMPs except N6‐C14H29 were more potent activators of bovine myocardial protein kinase than cyclic AMP. The partition coefficients between octanol and an aqueous phase of N6‐R cyclic AMPs became greater as the numbers of carbon atoms increased, and there appeared to be a relationship between partition coefficient and inotropic potency. It was concluded that membrane penetrativeness rather than potency as activators of protein kinase determined the potencies of N6‐R cyclic AMPs as positive inotropic agents.
Derivatives such as N6‐C7H15 cyclic AMP, which have positive inotropic activity without any marked negative chronotropic effect, may be useful as cardiotonic agents in heart failure.
The cardiovascular pharmacology of ICI 170777 ((6RS)−6‐methyl‐5‐(pyrid‐4‐yl)−3H,6H‐1,3,4‐thiadiazin‐2‐one) a novel compound with positive inotropic and vasodilator effects
Authors: Collis M.G. , Keddie J.R. , Rouse W. 
Published: July 2012

This paper describes the cardiovascular effects of ICI 170777, a novel compound which enhances cardiac contractility and causes arterial and venous dilatation.
The positive inotropic effects of ICI 170777 on the heart were demonstrated by an increase in left ventricular dP/dtmax in the anaesthetized and conscious dog, and by an increase in tension development in isolated papillary muscles from the cat.
In the anaesthetized dog, the positive inotropic effects of ICI 170777 and of isoprenaline were attenuated by atenolol (5 mg kg−1, i.v.). Atenolol displaced the dose‐response curve to ICI 170777 to the right by 4 fold but displaced the isoprenaline dose‐response curve to the right by 247 fold. In vitro, however, atenolol (10 μm) had no significant effect on the positive inotropic response to ICI 170777. In the ganglion‐blocked anaesthetized dog, infusion of a low dose of ICI 170777 which had no effect on the basal left ventricular dP/dtmax, selectively potentiated the positive inotropic effects of isoprenaline. These results indicate that ICI 170777 has both a non‐adrenoceptor‐mediated positive inotropic effect on the heart and also facilitates the β‐adrenoceptor‐mediated control of contractility.
In the denervated and perfused hind‐limb of the dog, ICI 170777 reduced arterial perfusion pressure and increased limb circumference at a constant arterial flow and venous pressure. This indicates that ICI 170777 has direct dilator actions on both arterial and venous vessels. In this preparation, diazoxide exerted an arterial selective vasodilator effect and sodium nitroprusside was a relatively selective venous dilator. ICI 170777 exhibited a balanced arterial and venous dilator effect which was intermediate in profile between that of diazoxide and that of sodium nitroprusside.
In the conscious dog, low doses (2–5 mg kg−1, orally) of ICI 170777 evoked an increase in left ventricular dP/dtmax with no significant effect on heart rate or blood pressure. At a higher dose (10 mg kg−1, orally) it also reduced blood pressure and caused a significant increase in heart rate. The duration of the positive inotropic effect of 5 mg kg−1 (orally) of ICI 170777 was 10–12 hours. This response did not diminish following repeated administration of the compound.
The positive inotropic action and balanced arterial and venous dilator effect of ICI 170777 indicate that the compound may be useful in the treatment of congestive heart failure, a disorder that is characterized by decreased cardiac contractility and enhanced arterial and venous constrictor tone.
Prevention of physostigmine‐, DFP‐, and diazinon‐induced acute toxicity by monoethylcholine and N‐aminodeanol
Authors: Patterson T.A. , Terry A.V. , Kosh J. W. 
Published: July 2012

Choline, and the choline analogues monoethylcholine (MEC) and N‐aminodeanol (NAD) were examined for prophylactic activity in acute acetylcholinesterase inhibitor toxicity in mice. The rank order of potency of the compounds was MEC > NAD > choline.
Simultaneous administration of MEC (60 mg kg−1) or NAD (200 mg kg−1) with physostigmine reduced lethality to 17 and 13% respectively. MEC (60 mg kg−1) completely protected against di‐isopropylfluorophosphate (DFP) and diazinon toxicity, and NAD reduced lethality to 17% for both agents. Choline (200 mg kg−1) exhibited only negligible antidotal activity against the inhibitors.
In vitro concentrations of choline, MEC, and NAD, similar to the estimated concentration obtained in vivo in the acute toxicity study, produced mixed inhibition of mouse brain acetylcholinesterase. The inhibition was dose‐related and was additive to the inhibition produced by the cholinesterase inhibitors.
All three analogues reduced ligand binding at the nicotinic, M1, and M2 receptors. The rank order of potencies for the analogues at each receptor was nicotinic: (choline > MEC > NAD), M1: (MEC > choline > NAD), and M2: (MEC > choline > NAD).
It is proposed that the analogues prevent acetylcholinesterase inhibitor toxicity peripherally by interacting with acetylcholinesterase, and/or by competing with acetylcholine for binding to cholinoceptors.
Divalent cation dependence of the inhibition by phenothiazines of mediator release from mast cells
Authors: Peachell Peter T. , Pearce Frederick L. 
Published: July 2012

The divalent cations calcium, strontium and barium — and in that order of decreasing effectiveness — were capable of supporting the stimulated release of histamine from rat peritoneal mast cells (RPMC).
The responsiveness of mast cells to stimulation in the presence of divalent cations was, in general, markedly enhanced when the cells were first depleted of their intracellular calcium stores.
The putative calmodulin antagonists, chlorpromazine, promethazine, thioridazine (phenothiazines) and W‐7 (a naphthalene sulphonamide) all inhibited histamine release in the presence of divalent cations in both untreated cells and in RPMC depleted of their intracellular calcium.
Histamine release induced by antigen, compound 48/80 and ionophore A23187 was inhibited by this class of compounds most effectively in the presence of extracellular barium, less so in the presence of strontium and least so in calcium‐containing media.
In the experimental situation where the extracellular calcium concentration was reduced (< 1 mm), the phenothiazines inhibited the stimulated release of histamine more effectively.
In toto, these results suggest that strontium and barium, as well as calcium, can support histamine release from RPMC by directly interacting with an intracellular divalent cation‐binding site that may be calmodulin. As a consequence, one mechanism by which the phenothiazines and W‐7 may modulate the secretory response could reflect an antagonism of a divalent cation interaction at that same site, although other additional potential sites of inhibitory action are indicated, dependent on the stimulus employed for secretion.
Depression of maximum rate of depolarization of guinea‐pig ventricular action potentials by metabolites of encainide
Authors: Hemsworth Paul D. , Campbell Terence J. 
Published: July 2012

Standard microelectrode methods have been used to record action potentials from guinea‐pig ventricular myocardium and dog Purkinje fibres, and to study the effects of the two major metabolites of encainide, O‐desmethyl encainide (ODE) and 3‐methoxy‐O‐desmethyl encainide (MODE).
In concentrations similar to those found in patients during chronic encainide therapy, neither ODE nor MODE produced significant depression of maximum rate of depolarization () of action potentials in unstimulated tissue. Repetitive stimulation, however, was associated with depression of which increased with increasing driving rates (rate‐dependent block, RDB). At the fastest rate studied (interstimulus interval = 300 ms) ODE 1 μm depressed by 47.5 ± 5.7% and MODE 1 μm, reduced by 52.2 ± 12%.
The onset and offset kinetics of this rate‐dependent block were very slow. Full development of RDB during a train required over 100 action potentials and the time constants of recovery of from RDB were 86.4 ± 37 s for ODE and 100.4 ± 18 s for MODE. The amount of RDB and its rate of onset increased with drug concentration. The recovery time constants were independent of interstimulus interval or drug concentration. Both metabolites also produced rate‐dependent depression of conduction velocity in canine Purkinje fibres, but no evidence of selective depression of conduction of interpolated premature potentials was seen.
Early afterdepolarizations occurred spontaneously in three preparations in the presence of MODE, 1 μm and one preparation in ODE, 1 μm.
It is concluded that these metabolites of encainide may play a role in producing both its antiarrhythmic and its proarrhythmic effects.
Investigation of the vasoconstrictor action of subarachnoid haemoglobin in the pig cerebral circulation in vivo
Authors: Byrne J.V. , Griffith T.M. , Edwards D.H. , Harrison T.J. , Johnston K.R. 
Published: July 2012

Angiographic techniques have been used to study the influence of intracisternally injected haemoglobin on the diameters of the main intrathecal and representative extrathecal (ascending pharyngeal and facial) cranial arteries of the anaesthetized pig.
Intracisternal injection of haemoglobin caused concentration‐dependent decreases in the diameters of intra‐ but not extrathecal arteries suggesting that haemoglobin possesses local vasoconstrictor activity.
When infused into one ascending pharyngeal artery, acetylcholine (ACh) caused slight dilatation of the intrathecal arteries but no change in the diameters of the ascending pharyngeal and facial arteries. The dilator response induced by ACh in the intrathecal arteries was converted into frank constriction after intracisternal injection of haemoglobin (cerebrospinal fluid concentration approximately 2 × 10−5 m).
These findings are consistent with the hypothesis that subarachnoid haemoglobin can induce cerebral artery constriction by acting as an extraluminal ‘sink’ for intimally released endothelium‐derived relaxing factor (EDRF) and may be relevant to the pathogenesis of vasospasm after subarachnoid haemorrhage in man.
Cholecystokinin‐octapeptide constricts guinea‐pig and human airways
Authors: Stretton C.D. , Barnes P.J. 
Published: July 2012

Cholecystokinin‐octapeptide (CCK‐OP, 10−10‐3 × 10−6 m) produced a concentration‐dependent contractile response in guinea‐pig trachea which was enhanced by both the mechanical removal of the epithelium and by indomethacin (10−5 m), with an EC50 of 6.18 ± 0.10 × 10−8 m.
Sub‐threshold concentrations of CCK‐OP, which did not alter the resting tone of the smooth muscle, did not alter responses produced to electrical field stimulation (EFS) or to vagal nerve stimulation in an intact tracheal tube preparation. Atropine (2 × 10−6 m) did not alter the concentration‐response curve to CCK‐OP, indicating that CCK‐OP contraction is not mediated by cholinergic mechanisms.
The inhibition of neutral endopeptidase (endopeptidase‐24.11).by phosphoramidon (10−5 m) gave a leftward shift in the CCK‐OP concentration‐response curve in tissues with intact epithelium obtained from normal animals, but had no effect in tissues denuded of epithelium or in tissues obtained from animals which had been actively sensitized and challenged with ovalbumin (OA).
CCK‐OP‐induced contractile responses were antagonized by the CCK‐receptor antagonists dibutyryl cyclic guanosine monophosphate (pA2 = 4.3) and L‐364,718 (pA2 = 9.6).
CCK‐OP induced bronchoconstriction in large, but not small, human airways and was antagonized by the CCK‐receptor antagonist L‐364,718. CCK‐OP had no effect on cholinergic neural responses elicited by EFS in human airways.
β‐Adrenoceptor blocking effects of a selective β2‐agonist, mabuterol, on the isolated, blood‐perfused right atrium of the dog
Authors: Akahane Kunio , Furukawa Yasuyuki , Ogiwara Yasuhiro , Haniuda Masayuki , Chiba Shigetoshi 
Published: July 2012

Effects of (±)−1‐(4‐amino‐3‐chloro‐5‐trifluoromethyl‐phenyl)−2‐tert.‐butylamino‐ethanol hydrochloride (mabuterol) on pacemaker activity and atrial contractility were investigated in the isolated and blood‐perfused right atrium of the dog.
Mabuterol, injected into the sinus node artery of the isolated atrium, dose‐dependently increased atrial rate and contractile force at doses of 0.01–10 nmol but the responses to over 10 nmol of mabuterol gradually decreased and mabuterol at higher doses induced biphasic cardiac responses, i.e., negative followed by positive cardiac responses.
The maximal increases in atrial rate and contractile force induced by mabuterol were 41.4% and 12.9%, respectively, of the maximal chronotropic and inotropic effects of isoprenaline.
Positive chronotropic and inotropic responses to mabuterol were dose‐dependently inhibited by a selective β2‐adrenoceptor antagonist, ICI 118,551. These responses were only slightly attenuated by atenolol.
Mabuterol (1–300 nmol) dose‐dependently inhibited both dobutamine‐ and procaterol‐induced positive chronotropic and inotropic responses.
These results indicate that mabuterol causes weak positive chronotropic and inotropic effects on the perfused canine right atrium by activating β2‐adrenoceptors, and that higher concentrations non‐selectively block both β1‐ and β2‐adrenoceptors.
Developmental disappearance of excitatory α1 adrenoceptor function in the oesophagus of chick embryo
Authors: Miyazaki Hideto , Taneike Tetsuro , Ohga Akira 
Published: July 2012

Developmental change in the response to noradrenaline (NA) and 5‐hydroxytryptamine (5‐HT) was investigated in the chick oesophagus between 9 and 21 days of incubation and 4 days after hatching.
NA (5 μm) produced a significant contraction in the oesophagus at 9 days of incubation. The NA‐induced contraction progressively decreased with development and changed to an inhibition of spontaneous contraction or a small relaxation by 17 days of incubation.
The NA‐induced contractile response was inhibited by phentolamine (2.7 μm) and prazosin (0.55 μm). Phenylephrine (5 μm) but not clonidine (5–50 μm), also induced a contraction at early stages. The relaxation response to NA was sensitive to the β‐receptor blocker, carteolol (3.4 μm).
Pretreatment with carteolol unmasked the contractile responses to NA in preparations at 17–19 days of incubation. However, even in the presence of carteolol, the contraction produced by NA decreased and disappeared by the time of hatching. This change in response to NA is accompanied by a decline in the pD2 value. The response to phenylephrine (5 μm) followed the same pattern as that to NA.
The maximum binding sites of [3H]‐dihydroergocryptine to the crude membrane preparation from oesophagus changed little at 13, 17 and 21 days of incubation.
Isoprenaline (Iso, 0.01–20 μm) caused a carteolol‐sensitive relaxation in the carbachol‐contracted oesophagus after 13 days of incubation. The sensitivity (pD2 value) to Iso decreased slightly up to 17 days of incubation.
5‐HT (10 μm) caused a contraction in the oesophagus after 13 days of incubation and the amplitude of the response increased up to 17 days of incubation. The response to 5‐HT was abolished by methysergide (1 μm) but not by tetrodotoxin (0.78 μm) or atropine (1 μm) at every stage tested.
These results suggest that the response to NA changed from an α1‐adrenoceptor‐mediated contraction to a β‐receptor‐mediated relaxation during the embryonic period, resulting partly from the decline and disappearance of excitatory α1 ‐receptor function in the chick oesophagus.
Effect of chronic intra‐accumbens administration of the TRH analogue CG3509 on histamine‐induced behaviour in the rat
Authors: Bristow L.J. , Bennett G.W. 
Published: July 2012

The present study has investigated the effect of chronic intra‐accumbens administration of the thyrotrophin‐releasing hormone (TRH) analogue, CG3509, on CG3509‐ and histamine‐induced spontaneous motor activity and brain TRH‐like immunoreactive (TRH‐LI) levels in the rat.
Chronic intra‐accumbens administration of CG3509 (5 × 5 μg over 3 days) induced: (a) a significant (P <0.05) reduction in intra‐accumbens CG3509 (0.5 μg)‐induced hyperactivity, (b) reduced levels of TRH‐LI in the nucleus accumbens but not other brain regions, (c) a marked increase (107%, P < 0.01) in histamine‐induced non‐locomotor hyperactivity.
The present results demonstrate that alteration of central TRH function following treatment with a TRH analogue enhances the effect of intra‐accumbens histamine on behavioural hyperactivity, possibly via changes in H1 receptors and suggest that the neuropeptide, TRH and histamine interact in behavioural arousal mechanisms in rat brain.