bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of diltiazem on electrical responses evoked spontaneously or by electrical stimulation in the antrum smooth muscle cells of the guinea‐pig stomach
Authors: Ishikawa Shiro , Komori Kimihiro , Nagao Tetsuhiko , Suzuki Hikaru 
Published: July 2012

In circular smooth muscle cells of the guinea‐pig stomach (antrum), diltiazem (10−6 − 10−5 M) blocked the overshooting spike potential generated either spontaneously or by electrical stimulation in the presence of 2 mM tetraethylammonium chloride, but did not block the slow wave and the abortive spike potential.
The membrane was depolarized by high concentrations of diltiazem (more than 3 × 10−6 M), and this depolarization was associated with an increase in the membrane resistance.
The interval between slow waves was shortened to about 0.90 times the control (14.7 s) by 10−5 M diltiazem.
Transmural nerve stimulation evoked an inhibitory junction potential (i.j.p.) and enhanced the subsequently generated slow wave. Tetrodotoxin (3 × 10−7 M) blocked both responses but atropine (10−6 M) blocked only the latter.
Diltiazem (more than 10−6 M) increased the amplitude of the i.j.p. and depressed the enhancement of the slow wave produced by transmural nerve stimulation, presumably due to depolarization of the membrane. The latency for the i.j.p. remained the same in the presence of diltiazem (10−5 M).
It is concluded that in the guinea‐pig stomach, diltiazem blocks Ca‐influx during the generation of the overshooting spike potential, but not the Ca‐influx related to generation of the abortive spike potential or the slow wave. The cholinergic excitatory and the non‐adrenergic, non‐cholinergic inhibitory transmission may not be much affected by diltiazem.
The effects of adrenoceptor agonists and antagonists on plasma potassium concentration in anaesthetized guinea‐pigs, rabbits and rats
Authors: Coats Rachel A. 
Published: July 2012

An intravenous K+‐sensitive electrode has been used to monitor plasma [K+] changes induced by α‐ and β‐adrenoceptor agonists in anaesthetized guinea‐pigs, rabbits and rats. The effects of phentolamine and propranolol on these responses were studied.
In the guinea‐pig both α‐ and β‐adrenoceptor agonists produced a biphasic response consisting of an initial rapid increase in [K+] which was followed, within 1 min, by a fall below baseline. The antagonist studies indicated that in this species both phases of the response could be elicited by either α‐or β‐adrenoceptor activation.
In the rabbit the responses were both slower and smaller than those seen in the guinea‐pig and required larger agonist doses. In addition it was found that the increase in plasma [K+] was α‐adrenoceptor‐mediated while the subsequent fall was seen only with β‐adrenoceptor activation.
In the rat triphasic changes in plasma [K+] were seen consisting of an initial decrease which was α‐adrenoceptor‐mediated, followed by an increase and then a second fall which was elicited by β‐adrenoceptor stimulation. The increase in plasma [K+] was only slightly reduced by either α‐ or β‐adrenoceptor antagonists.
Apamin, a toxin from bee venom which blocks Ca2+‐activated K+‐channels, was found to block the hyperkalaemic phase of the response in the guinea‐pig and rabbit but had no effect in the rat.
It is concluded that there are marked species differences in the effects of adrenoceptor agonists on plasma [K+] in vivo.1
Cholinesterase activity and exposure time to acetylcholine as factors influencing the muscarinic inhibition of [3H]‐noradrenaline overflow from guinea‐ pig isolated atria
Authors: Fuder H. , Muscholl E. , Wolf K. 
Published: July 2012

Guinea‐pig isolated atria were incubated and loaded with [3H]‐noradrenaline. The release of 3H and of [3H]‐noradrenaline was induced by field stimulation (6–9 trains of 150 pulses at 5 Hz). The stimulation‐evoked overflows of 3H and of [3H]‐noradrenaline were determined.
In the absence of an inhibitor of acetylcholinesterase, acetylcholine (12 min preincubation before nerve stimulation, up to 10 μM) failed to inhibit the evoked [3H]‐noradrenaline overflow. In the presence of atropine, an increase by acetylcholine of evoked release was observed in the same atria. In contrast, the selective muscarinic agonist methacholine significantly decreased the evoked overflow. The inhibition was antagonized by atropine. Methacholine did not enhance release in the presence of atropine.
When present for only 2 min, acetylcholine 10 μM inhibited the evoked overflow and no facilitation of release was observed in the presence of atropine.
In the presence of physostigmine, acetylcholine (12 min preincubation, 1 and 10 μM) inhibited evoked [3H]‐noradrenaline overflow, but the overflow was increased by acetylcholine 10 μM in the presence of atropine.
In the presence of cocaine, corticosterone, phentolamine, propranolol and hexamethonium together, acetylcholine 1 μM inhibited the evoked [3H]‐noradrenaline overflow. The inhibition was significantly enhanced in the presence of physostigmine. It decreased with preincubation time of the agonist, despite the presence of physostigmine and constant replacement by new drug. Neither inhibition nor facilitation of evoked release was observed in the presence of atropine.
It is concluded that a muscarinic inhibition by acetylcholine (upon prolonged exposure time) may be masked by a concomitant facilitation of release and/or desensitization of the muscarinic inhibitory mechanism. Furthermore, degradation by acetylcholinesterase contributes in part to the ineffectiveness of acetylcholine as a presynaptic inhibitor. When a distortion of the overflow/release ratio was excluded, adrenergic and nicotinic effects were prevented, and acetylcholinesterase was inhibited, the fading of muscarinic inhibition by acetylcholine may have been exclusively due to a slow and moderate desensitization of the presynaptic muscarinic mechanism.
Relationship between the stereoselective negative inotropic effects of verapamil enantiomers and their binding to putative calcium channels in human heart
Authors: Ferry D.R. , Glossmann H. , Kaumann A.J. 
Published: July 2012

Ventricular preparations from patients with mitral disease and hypertrophic obstructive cardiomyopathy (HOCM) were set up to contract isometrically. Ventricular membrane particles were also prepared and putative calcium channels were labelled with [3H]‐nimodipine.
Positive staircase was induced by varying the rate of stimulation of isolated strips from 6 min−1 to 120 min−1 in the presence of 6–60 μm (—)‐adrenaline or (—)‐noradrenaline. (—)‐Verapamil 3–5 μm or (+)‐verapamil 20–30 μm reversed the force‐frequency relationship (i.e. caused negative staircase) in preparations from patients with mitral disease or HOCM.
In subendocardial strips of ventricular septum from 5 patients with HOCM paced at 60 min−1, both (—)‐verapamil and (+)‐verapamil caused cardiodepression. Half‐maximal cardiodepression was observed with 0.4 μm (—)‐verapamil and with 3 μm (+)‐verapamil.
[3H]‐nimodipine bound to ventricular membrane particles in a saturable, reversible fashion to a high affinity site with an equilibrium dissociation constant of 0.23 nm. The density of these sites was 95 fmol mg−1 of membrane protein. Binding of the tritiated 1,4‐dihydropyridine was stereoselectively inhibited by 1,4‐dihydropyridine enantiomers and nifedipine.
(—)‐Verapamil and (+)‐verapamil inhibited high affinity [3H]‐nimodipine binding in a negative heterotropic allosteric manner with (—)‐verapamil being 5 times more potent than (+)‐verapamil on an IC50 basis. At a given [3H]‐nimodipine concentration, (+)‐verapamil inhibited a greater fraction of specific [3H]‐nimodipine binding.
The allosteric mode of (+)‐verapamil inhibition of [3H]‐nimodipine binding was confirmed by kinetic studies. (—)‐Verapamil shifted (+)‐verapamil‐binding inhibition curves to the right in an apparently competitive fashion.
The inversion of staircase caused by both verapamil enantiomers suggests that they cause a use‐dependent channel blockade. The similar potency ratios for binding and for cardiodepression are indicative of a common locus of action for both verapamil enantiomers within the calcium channel.
Characterization of pre‐ and postsynaptic actions of (—)‐baclofen in the guinea‐pig hippocampus in vitro
Authors: Inoue Masumi , Matsuo Tadashi , Ogata Nobukuni 
Published: July 2012

The effects of (—)‐baclofen on evoked potentials in the hippocampus were examined through intracellular recordings from guinea‐pig brain slices.
The evoked responses were recorded in two fibre connections within the hippocampus: the Schaffer collateral/commissural‐CA1 pyramidal cell, and the mossy fibre—CA3 pyramidal cell.
The Schaffer collateral/commissural‐CA1 response was suppressed by (—)‐baclofen in concentrations over 2 × 10−5m, whereas (+)‐baclofen, an inactive isomer, in a concentration of 10−4m had no effect on the response.
A compound action potential of Schaffer collateral/commissural axons was unaffected by (—)‐baclofen even at 10−4m, a concentration that almost completely depressed the evoked response in the CA1 pyramidal cell.
The mossy fibre—CA3 response was not inhibited by (—)‐baclofen (10−4m).
The depressant action of (—)‐baclofen on the Schaffer collateral/commissural—CA1 response was unaffected by bicuculline (10−4m), whereas the direct membrane effects of (—)‐baclofen were antagonized by bicuculline (10−5m).
It is suggested that (—)‐baclofen may modulate neuronal transmission through presynaptic recognition sites possibly by decreasing transmitter release from nerve terminals and also may directly regulate the endogenous neuronal excitability through an activation of the postsynaptic recognition sites.
Responses of the pig isolated renal artery to transmural electrical stimulation and drugs
Authors: Ferguson D.R. , Johnson B.I. , Price N. 
Published: July 2012

Pig isolated renal arteries contract in response to addition of noradrenaline, 5‐hydroxytryptamine, histamine, angiotensin II, vasopressin and carbachol, whereas cholecystokinin, adenosine, and inosine produce relaxation.
Transmural stimulation of the tissue causes contraction of circular muscle in the arterial wall which produces apparent elongation of the vessel.
The effects of transmural stimulation are partially blocked by prazosin and potentiated by propranolol, indicating that noradrenaline acts through both α‐ and β‐adrenoceptors.
Guanethidine (10−5m) reduces the size of responses to transmural stimulation in the presence of both prazosin (10−6m) and propranolol (10−7m).
Both saralasin (10−7 m), and desensitization of angiotensin II receptors by prolonged contact with the peptide, produced a reduction in response to transmural stimulation, indicating that angiotensin II may be involved in neurotransmission. This effect was blocked by tetrodotoxin.
Transmural stimulation produces relaxation of renal arteries in the presence of maximal doses of saralasin, prazosin, and propranolol, suggesting that a third unidentified substance is also released from autonomic nerves.
On the type of receptor involved in the inhibitory action of adenosine at the neuromuscular junction
Authors: Ribeiro J. A. , Sebastião A.M. 
Published: July 2012

The effects of adenosine and adenosine analogues (1‐N6‐phenylisopropyladenosine (1‐PIA), d‐N6‐phenylisopropyladenosine (d‐PIA), N6‐cyclohexyladenosine (CHA), N6‐methyladenosine, 5′‐N‐ethyl‐carboxamide adenosine (NECA) and 2‐chloroadenosine) on evoked endplate potentials (e.p.ps) and on twitch tension were investigated in innervated sartorius muscles of the frog.
Adenosine and its analogues decreased, in a concentration‐dependent manner, the amplitude of both the e.p.ps and the twitch responses evoked by indirect stimulation. The order of potencies in decreasing twitch tension was: 1‐PIA, CHA, NECA > 2‐chloroadenosine > d‐PIA > n6‐methyladenosine, adenosine. 1‐PIA was about ten fold more potent than d‐PIA.
None of the adenosine analogues tested affected the twitch responses of directly stimulated tubocurarine‐paralyzed muscles.
In concentrations that did not modify neuromuscular transmission, theophylline and 8‐phenylth‐eophylline (8‐PT) but not isobutylmethylxanthine (IBMX), antagonized the inhibitory action of 2‐chloroadenosine at the neuromuscular junction. 8‐PT behaved as a competitive antagonist and was about forty fold more potent than theophylline.
It is concluded that the R‐type adenosine receptor at the neuromuscular junction should not be classified in the A1/A2 system. The possibility of calcium‐linked adenosine receptors having pharmacological profiles distinct from those originally defined as modulating adenylate cyclase is discussed.
Effects of Bay K 8644 on contraction of the human isolated bronchus and guinea‐pig isolated trachea
Authors: Advenier Charles , Naline Emmanuel , Renier Annick 
Published: July 2012

The effects of Bay K 8644, a dihydropyridine which increases calcium flux through the potential‐operated channels were studied on the contractions induced by histamine, acetylcholine, KCl and Ca2+ on human isolated bronchial strips and the results were compared to those obtained on guinea‐pig isolated tracheal spirals. Subsequently the contractant effects of Bay K 8644 in K+‐enriched medium and in the presence of Ca2+ 0.03 mM were investigated.
In Krebs normal calcium medium, Bay K 8644 did not significantly modify the EC50 of acetylcholine or histamine on the human bronchus, but in concentrations of 10−7 − 10−6 M it potentiated the effects of KCl on that preparation. It did not modify the EC50 of acetylcholine, histamine or KCl on the guinea‐pig trachea.
In Ca2+‐free Krebs medium with additional K + (30 mM), Ca2+ concentration‐response curves were displaced to the left by Bay K 8644 in the two preparations. Shifts were 0.52 ± 0.11 and 0.72 ±0.16 log units respectively with Bay K 8644 10−8 and 10−7 M on human bronchus (n = 4) and 0.67 ± 0.16 and 1.06 ± 0.19 log units respectively with Bay K 8644 10−7 and 10−6 M on the guinea‐pig trachea (n = 5).
In Krebs medium with Ca2+ 0.03 mM and K+ 30 mM, Bay K 8644 (10−8 to 10−6 M) contracted both the human bronchus and the guinea‐pig isolated trachea. This effect was competitively antagonized by nicardipine.
These results demonstrate the presence of dihydropyridine sites of action on human bronchus and confirm the minor role played by Ca2+ influx through potential‐operated channels in the contractile effects of acetylcholine or histamine. They also demonstrate the similar reactivity of human bronchus and guinea‐pig isolated trachea to Bay K 8644.
Comparison of the effects of BRL 34915 and verapamil on electrical and mechanical activity in rat portal vein
Authors: Hamilton T.C. , Weir Sheila W. , Weston A.H. 
Published: July 2012

The effects of the novel anti‐hypertensive agent BRL 34915, (±) 6‐cyano‐3,4‐dihydro‐2,2‐dimethyl‐trans‐4‐(2‐oxo‐1‐pyrrolidyl)‐2H‐benzo[b]pyran‐3‐ol, have been compared with those of verapamil on rat isolated portal vein.
BRL 34915 produced a concentration‐dependent reduction in mechanical responses to noradrenaline but had relatively little inhibitory effect on K+‐induced contractions. Verapamil reduced the magnitude of both noradrenaline and K+‐induced mechanical responses.
BRL 34915 delayed the appearance of the reduced noradrenaline contractions, a property not shared by verapamil.
BRL 34915 abolished spontaneous electrical and mechanical discharges and hyperpolarized the portal vein cells close to their calculated potassium equilibrium potential. Verapamil inhibited spontaneous electrical and mechanical discharges, effects associated with a small depolarization.
BRL 34915 produced a significant increase in the 86Rb efflux rate coefficient whilst verapamil was without effect on this parameter.
The inhibitory effects of BRL 34915 were rapid in onset and readily reversible by washing, whilst those of verapamil were slower in onset and only slowly reversible.
It is concluded that the inhibitory effects of BRL 34915 in rat portal vein are produced by the opening of potassium channels in the smooth muscle cells. This inhibits spike activity and in sufficient concentration holds the membrane potential at or close to the potassium equilibrium potential, thereby reducing the effects of excitatory agents.
The effect of clonidine on venous haemodynamics in cats and dogs
Authors: Bentley G.A. , Cullen L.K. , Reynoldson J.A. , Widdop R.E. 
Published: July 2012

Experiments were undertaken to investigate a possible action of clonidine on venous haemodynamics, using cats and dogs with autoperfused hindquarters. This provided an arterial input to the region independent of cardiac output. Venous capacitance in the hindquarters was indicated by blood flow in the abdominal vena cava, as measured by an electromagnetic flow probe around this vessel.
It was found that in both cats and dogs, clonidine given intravenously (5 μg kg−1 i.v.) or into the cisterna magna (1 μg kg−1 i.c.m.) reduced mean arterial pressure and heart rate, but did not decrease hindquarter perfusion pressure. With the exception of dogs given i.v. clonidine, this drug caused a decrease in inferior vena cava (IVC) blood flow and this closely paralleled the hypotensive effect. However, when clonidine was given i.v. to dogs, the decrease in IVC blood flow preceded the hypotension. At the doses used, the reduction in IVC blood flow was larger following i.v. than i.c.m. clonidine in both species, and in all cases, it remained below control levels for at least 30 min, in spite of the constant arterial input to the region.
In cats, dose‐response curves were constructed to noradrenaline and adrenaline given into the perfusion circuit (i.a.) before and after clonidine. Following i.v. and i.c.m. clonidine, there was a selective depression of the venoconstrictor actions of the catecholamines, but no change in the arterial pressor action.
Radiographic and latex studies in the dog and cat respectively were performed in order to visualize collateral blood flow that could account for the persistent decreases in IVC blood flow. In both species, intraspinal collateral flows were demonstrated which returned blood to the heart after ligation of the inferior vena cava below the renal veins. However, it was not possible to demonstrate radiographically any changes produced by clonidine in the collateral flow because of technical difficulties.
These results suggest that clonidine causes a selective reduction in sympathetic tone to the veins that is mediated at least partly by a central action, as well as an expansion of the collateral venous routes. This, together with the selective impairment of venoconstrictor responses to both noradrenaline and adrenaline, may account for the decrease in cardiac output that is most often reported following clonidine.
Effects of Bay K 8644 and nifedipine on femoral arteries of spontaneously hypertensive rats
Authors: Aoki Kyuzo , Asano Masahisa 
Published: July 2012

Vasoconstrictor effects of Bay K 8644 (an agonist known to increase Ca2+ influx through the voltage‐dependent Ca2+ channels) on femoral arteries of 6 week old spontaneously hypertensive rats (SHR) were investigated, and data compared with findings in age‐matched normotensive Wistar‐Kyoto rats (WKY).
The addition of Bay K 8644 (1 × 10−10 − 3 × 10−7 M) elicited a dose‐dependent contraction in SHR femoral artery in the absence of any contractile agent. Maximum contraction induced by this agonist was the same as the maximum induced by either K+‐depolarization or α‐adrenoceptor stimulation.
Bay K 8644 was less effective in eliciting a contraction in the WKY femoral artery.
Increased sensitivity to K+ was also observed in the SHR femoral artery. In contrast, contractions in response to α‐adrenoceptor stimulation were the same in the SHR as those in the WKY.
The addition of nifedipine, a Ca2+ channel antagonist, to an unstimulated preparation produced a dose‐dependent relaxation in femoral arteries from SHR, but not from WKY. When the arteries were contracted with 60 mM K+, nifedipine produced similar relaxations in the SHR as those in the WKY, suggesting that the Ca2+ channels in the SHR femoral arteries are more activated than those in the WKY femoral arteries.
Contractile responses of SHR femoral arteries to Bay K 8644 were antagonized competitively by nifedipine.
Contractile responses to Ca2+ determined in K+‐depolarized strips were also antagonized competitively by nifedipine. However, Schild plot analysis clearly demonstrated a different pA2 value for nifedipine, suggesting that there may be a difference in the state of voltage‐dependent Ca2+ channels in SHR femoral artery between the stimulation with Bay K 8644 and K+‐depolarization.
A comparison of the binding of σ opioids and phencyclidine, and the interaction with antipsychotic drugs in rat brain membranes
Authors: Downes C.P. , Lewis P.E. , Stone M.A. 
Published: July 2012

The present study investigates the relationship between binding at the s̀ site labelled by the prototypic s̀ ligand (+)‐[3H]‐N‐allylnormetazocine ((+)‐[3H]‐SKF10,047) and binding at the phencyclidine (PCP) site labelled by [3H]‐phencyclidine in rat whole brain membranes.
(+)‐[3H]‐SKF10,047 bound with a KD of 251 ± 66 nM. [3H]‐PCP bound with a KD of 180 ± 35 nM (KD ± asymptotic s.e.).
The potencies of a range of compounds to displace these ligands were only poorly correlated (r = 0.3). Furthermore selective displacement of (+)‐[3H]‐SKF10,047 but not of [3H]‐PCP was demonstrated using the non‐selective dopamine ligand haloperidol and the dopamine2‐selective ligand 3‐(3‐hydroxyphenyl)N‐n‐propylpiperidine (3PPP). These results indicate that the s̀ and PCP sites are different entities.
The relationship between binding at the s̀ site and dopamine receptors was investigated in rat whole brain membranes and in striatal membranes.
(±)‐SKF10,047 displaced [3H]‐haloperidol bound to whole brain membranes with a greater potency than it displaced [3H]‐haloperidol bound to striatal membranes. The opposite was true for the dopamine antagonist, clozapine, which showed greater potency in striatal membranes.
Comparison of [3H]‐haloperidol binding in whole brain and striatum gave only a poor correlation (r = 0.6). Hence, different binding sites would appear to exist in these brain regions, the binding of [3H]‐haloperidol to whole brain being predominantly to s̀ sites and the binding to striatum being predominantly to dopamine receptors.
Autonomic responses of the isolated, innervated trachea of the guinea‐pig: interaction with autonomic drugs, histamine and 5‐hydroxytryptamine
Authors: McCaig Dorothy J. 
Published: July 2012

Intraluminal pressure was measured in the isolated, fluid‐filled trachea of the guinea pig, with autonomic innervation on the right side intact. Increases or decreases in intraluminal pressure reflected excitatory or inhibitory responses respectively, in the tracheal smooth muscle.
Stimulation of the cervical vagus nerve evoked a cholinergic excitatory response. After cholinergic blockade with atropine, a non‐adrenergic, non‐cholinergic inhibitory response was obtained.
Stimulation of the cervical sympathetic trunk, or stellate ganglion, evoked β‐adrenergic inhibitory responses. In the presence of propranolol, sympathetic stimulation evoked α‐adrenergic excitatory responses which were of low amplitude (< 5% of cholinergic excitatory responses). In the presence of phentolamine but not prazosin, β‐adrenergic inhibitory responses were potentiated.
Neostigmine potentiated responses to vagal stimulation, increasing the amplitude and duration of response. At higher concentrations neostigmine (i) raised intraluminal pressure, a response blocked by atropine, and (ii) attenuated sympathetic inhibitory responses, an effect largely blocked by atropine.
Histamine increased intraluminal pressure and this response was attenuated by atropine. In the presence of histamine, vagal excitatory responses were attenuated. Sympathetic inhibitory responses at low frequencies of stimulation (up to 10 Hz) were inhibited by histamine.
5‐Hydroxytryptamine (5‐HT) increased intraluminal pressure also, an effect partially blocked by atropine. 5‐HT had no effect on vagal excitatory responses. Like histamine, 5‐HT attenuated sympathetic inhibitory responses at lower frequencies of stimulation.