bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of charybdotoxin, a blocker of Ca2+ ‐activated K + channels, on motor nerve terminals
Authors: Anderson A.J. , Harvey A.L. , Rowan E.G. , Strong P.N. 
Published: July 2012

The contribution of Ca2+‐activated K+ currents (IK,Ca)to the control of electrical excitability of motor nerve terminals and the control of acetylcholine release was assessed by studying the effects of the specific K(Ca) channel blocking toxins charybdotoxin and apamin. Electrical activity of the terminal regions of motor nerves was assessed by extracellular recording from an electrode placed in the perineural sheaths of nerves in the mouse triangularis sterni and frog cutaneous pectoris preparations. Acetylcholine release was monitored by intracellular recording of endplate potentials (e.p.ps).
Charybdotoxin (20–300 nm), but not apamin (10nM‐2.5 μm), selectively reduced the amplitude of an IK,Ca unmasked by prior blockade of the delayed rectifier K+ current with 3,4‐diaminopyridine (3,4‐DAP).
In the combined presence of 3,4‐DAP and charybdotoxin, large Ca2+‐dependent plateau responses developed, but only moderate and transient increases in acetylcholine release occurred.
In the absence of 3,4‐DAP, charybdotoxin did not alter the electrical activity of, or the transmitter release from motor nerve terminals.
A possible role of the charybdotoxin‐sensitive IK,Ca in the control of transmitter release is discussed.
Alfaxalone potentiates and mimics GABA‐induced contractile responses in the guinea‐pig isolated ileum
Authors: Ong Jennifer , Kerr David I.B. , Johnston Graham A.R. 
Published: July 2012

Alfaxalone (1–100 nM) potentiated γ‐aminobutyric acidA (GABAA)‐receptor‐mediated contractile responses in the guinea‐pig isolated ileum, with a leftward shift of the GABA concentration‐response curve, and a significant potentiation of the GABA‐induced contractions over the lower concentration‐range for GABA (3–30 μM). Alfadalone on the other hand, did not affect contractile responses to GABA.
Picrotoxinin (10 μM) induced a non‐parallel rightward shift of the GABA concentration‐response curve, with a 50% depression of the maximum response to GABA. Alfaxalone (100 nM) potentiated the responses to GABA in the presence of picrotoxinin (10 μM) over the GABA concentration‐range of 10–100 μM, causing a leftward shift of the concentration‐response curve, but without affecting the depression of the maximum response by picrotoxinin.
Bicuculline methochloride (10 μM) caused a parallel rightward shift of the GABA concentration‐response curve; the ratio of this shift was unchanged in the presence of alfaxalone (100 μM), although the latter itself displaced the curve leftwards.
Alfaxalone (1–100 mM) also induced a similar potentiation of contractile responses to 3‐amino‐1‐propanesulphonic acid (3‐APS), a GABA agonist not subject to uptake. Such concentrations of alfaxalone were ineffective against contractile responses to exogenous acetylcholine.
Higher concentrations of alfaxalone (1 μM and above), however, elicited a GABA‐like ileal contraction, sensitive to both picrotoxinin (10 μM) and bicuculline (10 μM).
In conclusion, alfaxalone potentiated GABAA‐receptor‐mediated contractile responses in the guinea‐pig isolated ileum by acting at a modulatory site on GABAA‐receptor‐chloride‐ionophore complexes of GABA‐sensitive myenteric neurones, whilst high concentrations of alfaxalone exhibited a GABA‐mimetic action at GABAA‐receptors in the ileum. It is suggested that more than one site may exist where steroids interact with the GABAA‐receptor‐ionophore complexes.
Presence of a substance P‐like peptide in an acid extract of the intestinal bulb of the carp (Cyprinus carpio)
Authors: Kitazawa Takio , Kondo Hiroshi , Temma Kyosuke 
Published: July 2012

The effect of an acid extract of the carp intestinal bulb (ECI) on guinea‐pig ileum longitudinal smooth muscle (GPLM) and carp intestinal bulb longitudinal smooth muscle (CIBLM) was examined.
ECI caused a concentration‐dependent contraction of GPLM and CIBLM. This ECI‐induced response was reduced by atropine to 30–40% of the control, indicating that part of the contracting activity of ECI is attributable to acetylcholine. The atropine‐resistant contracting activity of ECI was not mediated by histamine, 5‐hydroxytryptamine, ATP, ADP, angiotensin II, neurotensin, vasoactive intestinal peptide or an opioid peptide.
The active material mediating the atropine‐resistant contracting activity is probably a peptide, because the contraction in response to ECI was abolished on incubation with pepsin or α‐chymotrypsin.
[D‐Pro2, D‐Trp7,9]‐substance P, [D‐Pro4, D‐Trp7,9]‐substance P (4–11) decreased the atropine‐resistant contracting activity of ECI as did desensitization induced by substance P.
On a Sephadex G 25 column, the active material was eluted as one peak. The active fractions were pooled and then applied to another Sephadex G25 column to compare the Ve/Vo value for the active material with those for peptides of known molecular weights. The molecular weight of the active material was estimated to be 1200–1700 (1410 ±70, n = 6).
The results indicate the presence of a substance P‐like peptide in the carp intestinal bulb.
Contribution of β1‐ and β2‐adrenoceptors of human atrium and ventricle to the effects of noradrenaline and adrenaline as assessed with (−)‐atenolol
Authors: Lemoine H. , Schönell H. , Kaumann A.J. 
Published: July 2012

(−)‐Atenolol was used as a tool to assess the function of β1 and β2‐adrenoceptors in human heart. Right atrial and left ventricular preparations from patients undergoing open heart surgery were set up to contract isometrically. Membrane particles were prepared for β‐adrenoceptor labelling with [3 H]‐(−)‐bupranolol and adenylate cyclase assays.
The positive inotropic effects of (−)‐noradrenaline were antagonized to a similar extent by (−)‐atenolol in atrial and ventricular preparations. (−)‐Atenolol consistently antagonized the effects of (−)‐adrenaline to a lesser extent than those of (−)‐noradrenaline in atrial preparations. In ventricular preparations (−)‐atenolol antagonized the effects of low concentrations of (−)‐adrenaline to a lesser extent than those of high concentrations.
pKB values (M) of (−)‐atenolol, estimated with non‐linear analysis from the blockade of the positive inotropic effects of the catecholamines, were 7.4 for β1‐adrenoceptors and 6.0 for β2‐adrenoceptors.
(−)−Atenolol inhibited the binding of [3 H]‐(−)‐bupranolol to ventricular β1‐adrenoceptors with a pKD (M) of 5.9 and to ventricular β2‐adrenoceptors with a pKD of 4.6.
(−)‐Atenolol inhibited the catecholamine‐induced adenylate cyclase stimulation in the atrium and ventricle with pKB values of 5.8‐6.4 for β1 and pKB values of 4.7‐5.7 for β2‐adrenoceptors. The binding and cyclase assays suggest a partial affinity loss for (−)‐atenolol inherent to membrane preparations.
β1 ‐Adrenoceptors mediate the maximum positive inotropic effects of (−)‐noradrenaline in both the atrium and ventricle of man. β2‐Adrenoceptors appear to be capable of mediating maximal positive inotropic effects of (−)‐adrenaline in atrium. In contrast, ventricular β2‐adrenoceptors mediate only submaximal effects of (−)‐adrenaline.
Elevation of intracellular cyclic AMP concentration fails to inhibit adrenaline‐induced hyperpolarization in amphibian sympathetic neurones
Authors: Zidichouski J.A. , Kehoe M.P. , Wong K. , Smith P.A. 
Published: July 2012

The effect of drugs on the adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) content of desmethylimipramine (DMI)‐treated bullfrog paravertebral sympathetic ganglia was studied by radioimmunoassay. The adrenaline‐induced hyperpolarization (Adh) in this tissue was recorded by means of the sucrose‐gap technique.
In the presence of propranolol (1 μm) and DMI (0.5 μm), adrenaline (1 μm) significantly reduced the concentration of cyclic AMP in forskolin‐treated ganglia. This effect was prevented by pertussis toxin (5 μg ml−1).
The relative potency for drugs which increased ganglionic cyclic AMP content was: 50 μm forskolin ≤ 5 mm fluoride > 2 mm fluoride > 2 mm isobutylmethylxanthine (IBMX) > 5 mm caffeine. In contrast, their relative potency for inhibition of the Adh was: 2 mm IBMX > 5 mm fluoride > 5 mm caffeine > 2 mm fluoride > 50 μm forskolin. The Adh was unaffected by pertussis toxin (5 μg ml−1).
Although the Adh was slightly reduced by the extracellular application of 8‐bromo (8‐Br) cyclic AMP, the majority of the data suggest that the transduction mechanism underlying the Adh is independent of the intracellular cyclic AMP concentration and provide an example of an α2‐adrenoceptor‐mediated response that occurs independently of inhibition of adenylate cyclase.
An evaluation of the structure‐activity relationships of a series of analogues of mephenesin and strychnine on the response to pressure in mice
Authors: Bowser‐Riley F. , Daniels S. , Hill W.A.G. , Smith E.B. 
Published: July 2012

A range of compounds structurally related to the centrally acting muscle relaxant mephenesin and to the chemical convulsant strychnine were synthesized and tested for their ability to alter the threshold pressures for the onset of high pressure convulsions in mice.
The ability of both groups of compounds to alter the threshold pressures for convulsions was found to be dependent on the nature of a simple molecular skeleton. Thus, compounds that possessed a negatively polarized group located both in the same plane as and some 4.5 A from an aromatic nucleus increased the thresholds whereas compounds with a positively polarized group at the same location reduced the thresholds.
These findings support the suggestion that pressure elicits convulsions via a selective action on a receptor protein complex rather than via some general perturbation of the lipid regions of cellular membranes.
Evidence that the hypertrophic action of clenbuterol on denervated rat muscle is not propranolol‐sensitive
Authors: Maltin C.A. , Hay S.M. , Delday M.I. , Reeds P.J. , Palmer R.M. 
Published: July 2012

The effect of propranolol on the clenbuterol‐induced protein anabolism in innervated and denervated soleus and plantaris muscles of the rat was studied.
The response to the β‐agonist, clenbuterol, in both innervated and denervated muscles, was not significantly inhibited by the β‐antagonist, propranolol.
The results provide further evidence to suggest that the action of clenbuterol on skeletal muscle protein accretion may not be directly mediated by β‐adrenoceptors.
Differential susceptibility of cholinergic and noncholinergic neurogenic responses to calcium channel blockers and low Ca2+ medium in rat urinary bladder
Authors: Bhat M.B. , Mishra S.K. , Raviprakash V. 
Published: July 2012

The influence of calcium channel blockers and low Ca2+ medium on the neurogenic responses to single pulse electric field stimulation in rat urinary bladder has been examined.
Single pulse stimulation evoked a biphasic contractile response consisting of a fast component with a time to peak of 0.72 ± 0.05 s and a slow component that reached a maximal tension at 2.8 ± 0.21 s, possibly mediated by two different neurotransmitters.
Atropine (3 × 10−6m) selectively inhibited the slow component without altering the fast component, suggesting the involvement of cholinergic and non‐cholinergic neurotransmitters, respectively.
Reducing Ca2+ in the medium to 1/4 of the normal, abolished the slow component of the neurogenic response while the fast contractile response was not altered which may indicate a relatively greater dependence of the cholinergic component on extracellular Ca2+ than the noncholinergic one.
The IC50 values for the fast component with respect to verapamil and diltiazem were 1.08 μm and 1.76 μm, respectively. The greater susceptibility of the slow component to calcium channel blockers (IC50 values of verapamil: 0.07 μm and of diltiazem: 0.25 μm) indicates the differential activation of slow calcium channels by the endogenously released substances.
Calcium channel blockers inhibited the ATP‐induced contraction which was comparable to that of the non‐cholinergic component of the neurogenic response suggesting the involvement of ATP as a possible neurotransmitter.
ACh‐induced contractions were relatively less susceptible to calcium channel blockers and low Ca2+ medium than was the atropine‐sensitive cholinergic component of the neurogenic response.
Effects of hypoxia on the pharmacological responsiveness of isolated coronary artery rings from the sheep
Authors: Kwan Y.W. , Wadsworth R.M. , Kane K.A. 
Published: July 2012

The effects of low oxygen tension on tone and on the responsiveness to contractile and relaxant agents were examined on circumflex coronary artery rings isolated from sheep.
When artery rings (2–2.5 mm o.d.) were set at their optimal resting tension, introduction of hypoxia (0% O2) caused a sustained contraction which was reversible on washing with oxygenated Krebs solution. In precontracted (40 mm KCl) arteries, hypoxia caused a similar response except that it was preceded by a transient relaxation.
The hypoxia‐induced contraction was potentiated by the combination of phentolamine (1 μm) and propranolol (1 μm), markedly reduced by verapamil (10 μm) and either abolished or reduced by indomethacin (1 μm). Indomethacin itself caused a contraction.
Under hypoxic conditions, the contractile effects of U46619 (a stable thromboxane analogue) and 5‐hydroxytryptamine (5‐HT) and the vasodilator effects of noradrenaline, iloprost (a prostacyclin mimetic) and adenosine were markedly potentiated. In contrast, vasoconstriction to potassium or acetylcholine was depressed.
Changing the gases from 95% O2 to 12% O2 had no significant effect on the contractile effects of U46619. However, the maximum contractile effect of U46619 was significantly enhanced by changing the gases from 12% O2 to 0% O2.
Rings from a smaller branch (0.6–1.3 mm o.d.) of the circumflex coronary artery of the sheep, in the presence of hypoxia, exhibited qualitatively similar changes in the responsiveness to U46619, 5‐HT and adenosine to those observed in the large artery. However, the effect of potassium was potentiated rather than depressed.
It is concluded that hypoxia‐induced contraction may involve a modified release of cyclo‐oxygenase products and be partly dependent upon the availability of extracellular calcium.
The change in the responsiveness of coronary arteries, under hypoxia, to both constrictor and dilator mediators may have clinical relevance to myocardial ischaemia and angina pectoris.
Hypoxia‐ and endothelium‐mediated changes in the pharmacological responsiveness of circumflex coronary artery rings from the sheep
Authors: Kwan Y.W. , Wadsworth R.M. , Kane K.A. 
Published: July 2012

The role(s) of the endothelium in modulating the responsiveness of isolated circumflex coronary artery rings (o.d. = 2.0–2.5 mm and o.d. = 0.6–1.3 mm) from sheep was investigated under oxygenated and hypoxic conditions.
Removal of the endothelium abolished the contraction produced by lowering the Po2 from 620 to 8 mmHg (either under optimal resting tension or precontracted by 40 mm KCl). In denuded artery rings sudden hypoxia caused relaxation.
Under oxygenated conditions, removal of the endothelium augmented the vasoconstrictor effects of U46619, 5‐hydroxytryptamine (5‐HT) and K+. In the denuded artery rings, hypoxia abolished the contractile effects of U46619 and reduced the contractile effects of 5‐HT and K+.
Under oxygenated conditions, the vasorelaxant effect of adenosine was depressed by removal of the endothelium. In endothelium‐denuded preparations, the small relaxant effect of adenosine remaining was greatly potentiated.
Haemolysate (1 μl ml−1) caused an endothelium‐dependent contraction under oxygenated conditions. The hypoxic contraction observed in the artery ring under resting tension was significantly potentiated by haemolysate (1 μl ml−l). Haemolysate 1 μl ml−l had no effect on the denuded artery rings under hypoxic conditions.
Haemolysate (1 μl ml−l) potentiated the vasoconstrictor effects of U46619 (0.5 μm), 5‐HT (1 μm) and K+ (24 mm) under oxygenated conditions.
These results indicate that endothelium profoundly modifies the effect of hypoxia on the responsiveness of sheep isolated left circumflex coronary artery rings.
Involvement of a pertussis toxin‐sensitive G‐protein in the pharmacological properties of septo‐hippocampal neurones
Authors: Rascol Olivier , Dutar Patrick , Lamour Yvon 
Published: July 2012

The physiological and pharmacological properties of identified septo‐hippocampal neurones (SHNs) have been studied in rats pretreated with the bacterial toxin, pertussis toxin (PTX).
In rats anaesthetized with urethane and pretreated with PTX, the axonal conduction velocity was unchanged while the mean spontaneous activity was significantly increased.
PTX pretreatment had no effect on responses of SHNs to the iontophoretic application of γ‐aminobutyric acid (GABA) and cholinoceptor agonists (acetylcholine or carbachol).
Baclofen and 5‐hydroxytryptamine (5‐HT), almost exclusively inhibitory in control rats, had little effect or an excitatory effect in PTX pretreated rats.
These results suggest the involvement of a pertussis toxin‐sensitive G‐protein in responses mediated by 5‐HT and GABAB‐receptors but not in responses mediated by cholinoceptors and GABAA‐receptors in medial septum neurones projecting into the hippocampus.
The properties of 5‐HT3 receptors in clonal cell lines studied by patch‐clamp techniques
Authors: Lambert Jeremy J. , Peters John A. , Hales Tim G. , Dempster John 
Published: July 2012

The characteristics of transmembrane currents evoked by 5‐hydroxytryptamine (5‐HT) in the neuroblastoma x Chinese hamster brain cell line NCB‐20 and neuroblastoma clonal cell line N1E‐115 have been studied under voltage‐clamp conditions by the whole‐cell recording and outside‐out membrane patch modes of the patch‐clamp technique.
In 73% of NCB‐20 cells examined (n = 221), and all N1E‐115 cells studied (n = 80), 5‐HT (10 μm) elicited a transient inward current at negative holding potentials, this being associated with an increase in membrane conductance. In both cell lines responses to 5‐HT reversed in sign at a potential of approximately −2mV and demonstrated inward rectification.
The reversal potential of 5‐HT‐induced currents (E5‐HT) recorded from either NCB‐20 or N1E‐115 cells was unaffected by total replacement of internal K+ by Cs+. In N1E‐115 cells, reducing internal K+ concentration from 140 to 20 mm produced a positive shift in E5‐HT of approximately 28 mV, whereas reducing external Na+ from 143 to 20 mm was associated with a negative shift in E5‐HT of about 37 mV. A large reduction in internal Cl− concentration (from 144 to 6 mm) had little effect on E5‐HT.
5‐HT‐induced currents of NCB‐20 cells were unaffected by methysergide (1 μm) or ketanserin (1 μm), but were reversibly antagonized by GR38032F (0.1–1.0 nm) with an IC50 of 0.25 nm. GR 38032F (0.3 nm) reduced 5‐HT‐induced currents in N1E‐115 cells to approximately 26% of their control value.
On outside‐out membrane patches excised from both NCB‐20 and N1E‐115 cells, 5‐HT induced small inward currents which could not be clearly resolved into discrete single channel events. Such responses were: (i) reversibly antagonized by GR 38032F (1 nm) (ii) reversed in sign at 0 mV, and (iii) subject to desensitization.
Fluctuation analysis of inward currents evoked by 5‐HT (1 μm) in N1E‐115 cells suggests that 5‐HT gates a channel with a conductance of approximately 310fS. Such a relatively small conductance could readily explain why the response of outside‐out membrane patches to 5‐HT cannot at present be resolved into clear single channel events.
The effect of medetomidine, an α2‐adrenoceptor agonist, on plasma atrial natriuretic peptide levels, haemodynamics and renal excretory function in spontaneously hypertensive and Wistar‐Kyoto rats
Authors: Ruskoaho Heikki , Leppäluoto Juhani 
Published: July 2012

The effects of the selective α2‐adrenoceptor agonist, medetomidine, were assessed on plasma levels of immunoreactive atrial natriuretic peptide (IR‐ANP), haemodynamics and on urine water and solute excretion in conscious, chronically cannulated, 7 month‐old spontaneously hypertensive (SHR) and age‐matched Wistar‐Kyoto (WKY) rats, in order to examine the role of α2‐adrenoceptors in the control of ANP secretion.
A 60 min i.v. infusion of medetomidine (0.2 or 0.6 μg kg−1 min−1) decreased heart rate dose‐dependently in both strains. Medetomidine infusion (0.6 μg kg−1 min−1) resulted in an increase in mean arterial pressure in WKY, whereas both doses decreased blood pressure in SHR. There was a slight increase in the right atrial pressure in both strains (WKY: + 1.18 ± 0.26 mmHg; SHR: + 1.64 ± 0.64 mmHg, NS) in response to infusion of 0.6 μg kg−1 min−1 of medetomidine.
No differences were found in resting plasma IR‐ANP levels between WKY (114 ± 8 pg ml−1, n = 19) and SHR (117 ± 10 pg ml−1, n = 21). Infusion of equibradycardic doses of medetomidine increased dose‐dependently plasma IR‐ANP levels in WKY, but did not affect the plasma IR‐ANP concentration in SHR rats.
Despite the different effect of medetomidine on ANP release in WKY and SHR rats, i.v. administration of medetomidine affected renal excretory functions similarly in both strains; urine flow and sodium excretion increased and urine osmolality decreased significantly, while there was no consistent change in urinary potassium excretion. Urine osmolality decreased to hypo‐osmotic levels during the infusion of 0.6 μg kg−1 min−1 of medetomidine, suggesting a possible interaction between α2‐adrenoceptor stimulation and the vasopressin system.
These results show that the α2‐adrenoceptor agonist medetomidine increased plasma levels of ANP in WKY rats, probably through an increase in mean arterial and right atrial pressures, whereas the SHR had attenuated ANP release to α2‐adrenoceptor stimulation. Our findings, that medetomidine caused marked natriuretic and diuretic effects in both strains and that these effects on the excretory functions of the kidneys were not related to changes in plasma levels of IR‐ANP, demonstrate that changes in plasma ANP levels alone do not account for the diuretic and natriuretic effect of α2‐agonists.
Evidence for a dihydropyridine‐sensitive and conotoxin‐insensitive release of noradrenaline and uptake of calcium in adrenal chromaffin cells
Authors: Owen P. Jane , Marriott Deborah B. , Boarder Michael R. 
Published: July 2012

It has been suggested that neuronal voltage‐sensitive calcium channels (VSCC) may be divided into dihydropyridine (DHP)‐sensitive (L) and DHP‐insensitive (N and T), and that both the L and the N type channels are attenuated by the peptide blocker ω‐conotoxin. Here the effects of ω‐conotoxin on release of noradrenaline and uptake of calcium in bovine adrenal chromaffin cells were investigated.
Release of noradrenaline in response to 25 mm K+, 65 mm K+, 10 nm bradykinin or 10 μm prostaglandin E1 was not affected by ω‐conotoxin in the range 10 nm‐1 μm.
45Ca2+ uptake stimulated by high K+ and prostaglandin was attenuated by 1 μm nitrendipine and enhanced by 1 μm Bay K 8644; these calcium fluxes were not modified by 20 nm ω‐conotoxin.
With superfused rat brain striatal slices in the same medium as the above cell studies, release of dopamine in response to 25 mm K+ was attenuated by 20 nm ω‐conotoxin.
These results show that in these neurone‐like cells, release may be effected by calcium influx through DHP‐sensitive but ω‐conotoxin‐insensitive VSCC, a result inconsistent with the suggestion that ω‐conotoxin blocks both L‐type and N‐type neuronal calcium channels.