bluuebunny/crossref_metadata_2025_split huggingface dataset:
Individual variations of prostanoid agonist responses in rabbit aorta: evidence for the independent regulation of prostanoid receptor subtypes
Authors: Keith Richard A. , Salama Andre I. 
Published: July 2012

The frequency and selectivity of individual variations of prostanoid agonist responses in aortic strips from a population of male rabbits was studied. Three levels of responsiveness to the thromboxane mimetic U46619 occurred: responders (R), intermediate responders (IR), and non‐responders (NR). R could be subdivided into R1 and R2 based on an enhanced potency of prostaglandin F2α (PGF2α) in R2. In the total population (n = 92), the phenotype frequency was: R, 69%; IR, 11%; and NR, 20%. In a subgroup of this population in which R1 and R2 phenotypes were determined (n = 63), the phenotype frequency was: R1, 54%; R2, 19%; IR, 6%; and NR, 21%.
The four rabbit aorta phenotypes, R1, R2, IR, and NR, were characterized with respect to the rank orders of prostanoid agonist potency, agonist intrinsic activities, and the effects of the thromboxane receptor antagonist SQ29548. The rank order of prostanoid agonist potency was U46619 > PGF2α > PGE2 in R1 and R2, and PGF2α > PGE2 > U46619 in IR and NR. For each prostanoid agonist, the intrinsic activity was highest in R (R1 ⋍ R2), intermediate in IR, and lowest in NR. In R1, SQ29548 inhibited all prostanoid agonist responses equally. The contractile effects of PGF2α and PGE2 were partially resistant to inhibition by SQ29548 in R2. Prostanoid agonist responses were not inhibited by SQ29548 in IR.
The potency of histamine was equivalent in R1, R2, IR, and NR.
It is concluded that there are individual variations in the functional expression of thromboxane receptor sensitivity, i.e., prostanoid agonist responses inhibited by SQ29548. Also, there are individual variations in the functional expression of the sensitivity of a non‐thromboxane receptor or receptors, i.e., prostanoid agonist responses not inhibited by SQ29548. It has been proposed by others that prostanoid receptors be termed P‐receptors and that the prostanoid agonist to which they are most sensitive be indicated by a preceding letter, e.g., TP‐for thromboxane receptor and FP‐for PGF2α‐selective receptor. Accordingly, we proposed a working hypothesis that suggests the four phenotypes could result from the independent regulation of the functional expression of TP‐and FP‐receptor subtypes with (a) R2 containing both the TP‐and FP‐receptor subtypes in a fully functional state; (b) R1 containing only the functional TP‐receptor; (c) IR containing only the functional FP‐receptor; and (d) NR containing only a low efficacy FP‐receptor system.
The mechanisms underlying the observed individual variations are unknown but could include changes in receptor number or affinity, changes in receptor‐effector coupling, changes in a second messenger system, or changes in tissue degradative or uptake processes. Further study is needed to differentiate between these possibilities.
Release of endogenous ATP during sympathetic nerve stimulation
Authors: Lew M.J. , White T.D. 
Published: July 2012

Vas deferens from guinea‐pig was stimulated with a suction electrode and both contractions and release of endogenous ATP monitored
Release of ATP was tetrodotoxin‐sensitive and increased when the number of stimuli was increased.
Release of ATP was not due to contraction of the muscle and persisted following block of contractions with prazosin and α,β‐methylene ATP.
These results indicate that stimulation of the sympathetic nerves in the vas deferens releases endogenous ATP presynaptically, supporting a cotransmitter function for ATP with noradrenaline.
Increase by oestrogen of calcium entry and calcium channel density in uterine smooth muscle
Authors: Batra S. 
Published: July 2012

The effect of in vivo oestrogen treatment on both 45Ca influx in myometrial strips and the kinetics of [3H)‐nitrendipine binding in the isolated plasma membrane (PM) was studied.
After four days of continuous oestrogen treatment of ovariectomized rats, 45Ca influx in both resting (unstimulated) and K‐stimulated myometrium was substantially increased.
Oestrogen treatment significantly increased the density in PM of nitrendipine binding sites and also caused a slight and insignificant increase in the affinity for nitrendipine.
The data suggest that the increase in Ca entry following oestrogen treatment prol ably results from an increase in calcium channel density.
Comparison of autonomic responses in the trachea isolated from normal and albumin‐sensitive guinea‐pigs
Authors: McCaig Dorothy J. 
Published: July 2012

Mechanical and electrical responses to stimulation of the parasympathetic and sympathetic nerves were compared in the trachea isolated from normal guinea‐pigs and from guinea‐pigs sensitized to albumin and exposed repeatedly to inhaled albumin (a model of bronchial asthma).
Sensitized trachealis exhibited mechanical hyper‐responsiveness to vagal stimulation characterized by a shift to the left of the frequency‐response relationship and a 71% increase in the maximum response.
Transmembrane potential was significantly less negative in sensitized trachealis cells.
The amplitude of the depolarization evoked by vagal stimulation (4 or more pulses) was significantly greater in sensitized tissues. Vagally‐mediated depolarization was associated with the appearance of regenerative electrical activity (spikes) in sensitized but not in control tissues.
Spontaneous discharge of slow waves occurred in cells from both control and sensitized trachea but the proportion of spontaneously active cells was higher in sensitized tissues. Spontaneous depolarization, like nerve‐mediated depolarization, gave rise to abortive spikes only in sensitized trachealis.
Inhibitory responses to stimulation of the sympathetic stellate ganglion, mediated by β‐adrenoceptors, were unaltered in sensitized trachealis.
Possible explanations for the hyper‐responsiveness to vagal input in sensitized trachealis are discussed.
Independent regulation of β1‐ and β2‐adrenoceptors
Authors: Beer Margaret , Hacker Stephen , Poat Judith , Stahl Stephen M. 
Published: July 2012

The down‐regulation of β‐adrenoceptors has been postulated as a biochemical marker of antidepressant efficacy. Here we demonstrate that chronic treatment with desipramine down‐regulates β1‐adrenoceptors in rat cerebral cortex and that β‐adrenoceptor subtypes can be independently regulated by treatment with different β‐adrenoceptor agonists.
Desipramine, (±)‐clenbuterol, prenalterol, corwin (20 mg kg−1 daily) and corwin (10 mg kg−1 daily) were administered to male, Sprague‐Dawley rats, over eight days, by means of osmotic Alzet pumps placed subcutaneously and removed 24 h before analysis. Control rats received vehicle only. The β1‐ and β2‐adrenoceptor populations were measured in cerebral cortex by a modified (–)‐[125I]‐pindolol receptor binding assay.
The conventional antidepressant, desipramine, preferentially down‐regulated β1‐adrenoceptors whereas the non‐selective β‐adrenoceptor agonist (±)‐clenbuterol preferentially down‐regulated β2‐adrenoceptors. The β1‐selective partial agonist, prenalterol, up‐regulated β1‐adrenoceptors perhaps acting more as an antagonist than as an agonist. Finally, neither dose of corwin had any significant effect on β‐adrenoceptor number.
Hypothermia induced by baclofen, a possible index of GABAB receptor function in mice, is enhanced by antidepressant drugs and ECS
Authors: Gray Julian A. , Goodwin Guy M. , Heal David J. , Green A. Richard 
Published: July 2012

Intraperitoneal injection to mice of the γ‐aminobutyric acidB (GABAB) receptor agonist (±)‐baclofen induces a dose‐dependent decrease in rectal temperature.
Injection of (–)‐baclofen intracerebroventricularly at doses that had no effect when given peripherally induced a marked hypothermia. (+)‐Baclofen was without effect.
The decrease in rectal temperature induced by (–)‐baclofen when injected intraperitoneally was highly correlated with an increase in sedation.
Repeated administration of amitriptyline (10 mg kg−1 daily for 14 days) resulted in mice displaying an enhanced temperature and sedation response to injection of (±)‐baclofen (5 mg kg−1) 24 h after the last dose of antidepressant.
An enhanced hypothermic response was also seen following repeated administration of zimeldine, mianserin or desipramine (all 10 mg kg−1 daily for 14 days) or repeated electroconvulsive shock (ECS; 5 ECS over 10 days) 24 h after the last treatment.
A single administration of any of the antidepressant drugs or ECS or repeated administration of the anxiolytic drug flurazepam (20 mg kg−1 daily for 14 days) did not alter the baclofen‐induced hypothermic response.
Administration of (±)‐baclofen (5 mg kg−1) daily for 5 or 14 days attenuated the baclofen‐induced hypothermic response. However, one pretreatment dose did not alter the response.
It has previously been reported that repeated baclofen administration decreases GABAB receptor number in the brain while repeated administration of antidepressant drugs and ECS increases the density of this receptor. The current data therefore suggest that baclofen‐induced hypothermia may provide a simple index of GABAB receptor function in the brain and strengthens the evidence that GABAB receptor function is enhanced by antidepressant drugs and ECS.
Electrophysiological studies of the effects of the general anaesthetic etomidate on frog myelinated nerve fibre
Authors: Benoit E. , Carratù M.R. , Dubois J. M. , Mitolo‐Chieppa D. , Preziosi P. 
Published: July 2012

The effects of the general anaesthetic etomidate (0.1 to 1 mmM) upon the node of Ranvier of frog isolated nerve fibres were investigated under current and voltage clamp conditions.
When added to the external solution, etomidate reversibly decreased the amplitude of the action potential. The action potential block, induced by the drug, was reversed by increasing the membrane potential.
Etomidate rapidly and reversibly blocked the Na current with an apparent dissociation constant of 0.6 mM. In the presence of the drug, the steady‐state inactivation‐voltage curve of the Na current was shifted towards negative voltages.
The block of Na current by etomidate was partially removed by repetitive depolarization preceded by a 50 ms period of hyperpolarization. In contrast, the block was enhanced when the repetitive depolarization was not preceded by hyperpolarization. This suggests that Na channels were preferentially blocked by the drug in the inactivated state.
The K current was reversibly blocked by etomidate with an apparent dissociation constant of 0.2 mM. In the presence of the drug, the K current showed an apparent fast inactivation suggesting that K channels were blocked in the open state.
We conclude that at higher concentrations than those attainable in the mammalian brain following single anaesthetic doses the general anaesthetic etomidate has a ‘local anaesthetic‐like’ action on the peripheral nervous system.
Nerve pathways involved in adrenergic regulation of electrical and mechanical activities in the chicken rectum
Authors: Komori Seiichi , Ohashi Hidenori 
Published: July 2012

Peripheral nerve pathways responsible for adrenergic inhibition of mechanical and electrical activities in the chicken rectum and receptors mediating the adrenergic inhibition were investigated in isolated extrinsically‐innervated rectum of the chicken.
Electrical stimulation of the anal end (Ra) or the ileal cut end (Ri) of Remak's nerve, or perivascular nerves (P) elicited relaxation of the rectum pretreated with atropine (0.5 μm) and hexamethonium (0.3 mm) to block the cholinergic and non‐cholinergic, non‐adrenergic excitatory innervations. Ri stimulation was much less effective than Ra and P stimulations. The relaxation was shown to be related to cessation of spontaneous spike discharge of the longitudinal muscle which was accompanied by membrane hyperpolarization.
The inhibitory effects elicited by Ra and P stimulations, which were prolonged beyond the period of the stimulation, were converted to transient ones by propranolol (3.4 μm). Phentolamine (2.6 μm) reduced effectively the residual effects. In contrast, the effects of Ri stimulation were little affected by these drugs.
The present results provide evidence for the existence of two nerve pathways responsible for direct adrenergic inhibitory innervation to the chicken rectum, one running orally in Remak's nerve trunk, leaving it and descending in the branches to the rectum, and the other running as the perivascular nerves along the arterial supplies of the rectum. The direct innervation is mediated predominantly by β‐adrenoceptors.
Purinoceptors in the rat heart
Authors: Fleetwood Gillian , Gordon John L. 
Published: July 2012

The effects of an intracoronary bolus of adenosine triphosphate (ATP), α,β‐methylene ATP (APCPP), β,γ‐methylene ATP (APPCP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and adenosine on coronary tone and ventricular myocardial contraction were investigated in the perfused rat heart.
Adenine nucleotides, given by bolus injection were negatively inotropic in amounts >3 × 10−7 mol. The potency order was ATP > ADP > AMP. Adenosine (< 1 × 10−5 mol) had no effect on ventricular myocardial contraction.
Adenine nucleotides and adenosine (1 × 10−10–1 × 10−7 mol) reduced coronary tone. The potency order was ATP > ADP > AMP = adenosine. The ATP analogue APPCP was less active than ATP at reducing coronary tone, and APCPP had no vasodilator effect. This suggests the presence of a P2‐purinoceptor, subclass P2Y, which mediates vasodilatation.
ATP and ADP increased the concentration of prostacyclin (measured as 6‐keto prostaglandin F1α) in the perfusate, but only after injection of > 3 × 10−7 mol, suggesting that the vasodilator responses to ATP and ADP were not mediated by prostacyclin. AMP and adenosine had no effect, even at 1 × 10−5mol.
At a dose of 3 × 10−9 mol, approximately 40% of ATP and 70% of ADP was converted to AMP and adenosine whilst passing through the heart. The amounts of AMP and adenosine formed, however, were insufficient to account for the vasodilator effects of ATP and ADP.
Vasodilatation mediated by AMP and adenosine was inhibited by an infusion of 8‐phenyltheophyllin (8‐PT; 2 × 10−5 m) indicating interaction with a P1‐purinoceptor. Vasodilatation induced by ATP (at doses at which AMP and adenosine had no action) was also depressed by 8‐PT indicating either an action of ATP on P1‐purinoceptors, or an effect of 8‐PT on P2Y receptors.
Vasodilatation induced by AMP was unaltered during an infusion of α,β‐methylene ADP (2 × 10−6 m, which inhibited breakdown of AMP to adenosine by 54.2 ± 1.5%, n = 4). This suggests that AMP acted directly, and it did not require conversion to adenosine to induce vasodilatation.
The ATP analogues APCPP (1 × 10−9 −1 × 10−8 mol) and APPCP (1 × 10−8−1 × 10−7 mol) increased coronary tone, as did high doses (1 × 10−5 mol) of ATP and ADP, indicating the presence of an additional P2‐purinoceptor, subclass P2X, mediating vasoconstriction.
Contractile effects of substance P and neurokinin A on the rat stomach in vivo and in vitro
Authors: Holzer‐Petsche Ulrike , Lembeck Fred , Seitz Helmut 
Published: July 2012

Substance P and neurokinin A (substance K) were infused into the coeliac artery of anaesthetized rats at doses of 0.06–20 nmol min−. Both tachykinins caused contractions of the stomach, the threshold dose of neurokinin A being 10 times lower than of substance P. The dose‐response curve for substance P was flatter than that for neurokinin A.
On circular muscle strips from the rat gastric corpus in vitro, the dose‐response curves for both tachykinins were parallel, neurokinin A being 10 times more potent than substance P. The contractions in response to 10 μm neurokinin A and to 30 μm substance P were 58 and 54%, respectively, of the maximal contraction to bethanechol (1 mm).
The effect of substance P was reduced by atropine both in vivo and in vitro. In vitro, the contractions to substance P were also reduced by tetrodotoxin but left unaffected by methysergide. The action of neurokinin A was not affected by these drugs.
It is concluded that neurokinin A contracts rat stomach by a direct action on the circular smooth muscle, whereas the action of substance P is mediated, at least in part, by cholinergic interneurones.
Morphine withdrawal in cortical slices: suppression by Ca2+‐channel inhibitors of abstinence‐induced [3H]‐noradrenaline release
Authors: Pellegrini‐Giampietro Domenico E. , Bacciottini Lucia , Carlà Vincenzo , Moroni Flavio 
Published: July 2012

The effects of morphine withdrawal were evaluated in vitro by monitoring the actions of naloxone on the depolarization‐induced release of [3H]‐noradrenaline (NA) in cortical slices taken from naïve or dependent rats. The effects of dihydropyridine molecules acting on Ca2+‐channels (nimodipine and Bay K 8644) were also studied in this model.
Naloxone (10−8‐10−5 M) dose‐dependently enhanced the K+ induced release of [3H]‐NA in slices taken from dependent rats, but failed to modify the [3H]‐NA release from ‘naïve’ slices.
The naloxone‐induced potentiation of release was significantly reversed by nimodipine (10−8‐10−6 M). These doses of nimodipine did not change [3H]‐NA release (both basal and K+ induced) in preparations obtained from naive rats.
Bay K 8644 potentiated the K+‐induced [3H]‐NA release from cortical slices taken from naïve rats to a similar extent as that of naloxone in dependent rats.
These results suggest that the naloxone potentiation of the depolarization‐induced [3H]‐NA release in slices taken from dependent rats may be considered a model of morphine withdrawal in vitro. In this model dihydropyridine Ca2+‐channel antagonists suppress morphine‐withdrawal effects in a similar manner to observations made in vivo.
A comparison between atria from control and streptozotocin‐diabetic rats: The effects of dietary myoinositol
Authors: Kofo‐Abayomi A. , Lucas P.D. 
Published: July 2012

Atria, isolated from control rats, six‐week streptozotocin‐diabetic rats and from similarly diabetic rats treated with myo‐inositol (MI) were compared. The MI treatment was shown to reverse the depressed sciatic nerve MI which was observed in the untreated diabetic group.
Spontaneously beating atria from the untreated diabetic animals beat more slowly, and with greater force than tissues from the control group. When electrically driven at 4 Hz they were found to be less sensitive to the negative inotropic effect of acetylcholine. No differences between the two groups were observed in responses to isoprenaline.
Intramural nerve stimulation in the presence of 10−6 m propranolol (vagal stimulation) had a greater negative inotropic effect in the untreated diabetic rat atria than in the controls. Positive inotropic responses to nerve stimulation in the presence of 10−6 m atropine (sympathetic stimulation) were not significantly different between the two groups.
Atria from the MI‐treated diabetic animals were found to have a lower spontaneous contractile force and greater sensitivity to acetylcholine than tissues from the untreated diabetic animals. The values obtained in both cases were similar to those from the controls. No significant effect of MI treatment on spontaneous contractile rate or on responses to nerve stimulation was demonstrated.
Atrial (mainly myocardial) MI was measured in additional control, six‐week diabetic and six‐week MI‐treated diabetic animals. A significantly higher concentration was observed in the MI supplemented group compared to the untreated diabetic group. The mean MI content in the latter group was lower than that obtained from control tissues but not significantly so.
The results implicate MI depletion either in the neurones or in the myocardium in at least some of the changes observed. Possible mechanisms involved are discussed.
Endothelium‐derived relaxing factor and atriopeptin II elevate cyclic GMP levels in pig aortic endothelial cells
Authors: Martin William , White David G. , Henderson Andrew H. 
Published: July 2012

Two directly‐acting stimulants of soluble guanylate cyclase, glyceryl trinitrate (0.1 μm) and sodium azide (10 μm), and a receptor‐mediated stimulant of particulate guanylate cyclase, atriopeptin II (10 nm), each elevated the cyclic GMP content of primary cultures of pig aortic endothelial cells without affecting the cyclic AMP content.
Two receptor‐mediated stimulants of adenylate cyclase, glucagon (1 μm) and isoprenaline (10 μm), had no effect on the cyclic AMP or cyclic GMP content of these cells, but the directly acting stimulant, forskolin (30 μm), induced a small increase in cyclic AMP content.
Three agents that release endothelium‐derived relaxing factor (EDRF); bradykinin (0.1 μm), ATP (10 μm) and ionophore A23187 (0.1 μm), each markedly elevated the cyclic GMP content of pig aortic endothelial cells, but acetylcholine (1 μm) had no effect. None of these agents had any effect on cyclic AMP content.
Two agents that potentiate the actions of EDRF; M & B 22948 (100 μm) and superoxide dismutase (30 units ml−1), each elevated the cyclic GMP content of pig aortic endothelial cells without affecting the cyclic AMP content. Pretreating cells with catalase (100 units ml−1) did not affect the rise in cyclic GMP content induced by superoxide dismutase (30 units ml−1).
Pretreatment of pig aortic endothelial cells with haemoglobin (10 μm) reduced the resting content of cyclic GMP and blocked the increase in cyclic GMP content induced by glyceryl trinitrate (0.1 μm), sodium azide (10 μm), bradykinin (0.1 μm) ATP (10 μm), ionophore A23187 (0.1 μm), M & B 22948 (100 μm) and superoxide dismutase (30 units ml−1), but not that induced by atriopeptin II (10 nm).
Pretreatment of pig aortic endothelial cells with an inhibitor of soluble guanylate cyclase, methylene blue (20 μm), had no effect on the resting content of cyclic GMP. Methylene blue (20 μm) blocked the increase in cyclic GMP content induced by glyceryl trinitrate (0.1 μm), M & B 22948 (100 μm) and bradykinin (0.1 μm), but not that induced by atriopeptin II (10 nm).
The data show that soluble guanylate cyclase, particulate guanylate cyclase and adenylate cyclase are present in pig aortic endothelial cells. They further suggest that EDRF, produced spontaneously or in response to vasoactive agents, elevates endothelial cyclic GMP content by stimulating soluble guanylate cyclase. It is possible that this may serve as a feedback loop by which the endothelial cell modulates EDRF production.
Noradrenaline stimulation of the phosphoinositide system: evidence for a novel hydrophobic inositol‐containing compound in resistance arterioles
Authors: Ollerenshaw J.D. , Heagerty A.M. , Swales J.D. 
Published: July 2012

Five inositol phosphates were extracted from adult rat resistance arterioles and separated by ion‐exchange high performance liquid chromatography.
By use of this technique, inositol phosphates liberated were identified as inositol 1‐phosphate, inositol 1,4‐bisphosphate, inositol 1,3,4‐trisphosphate, inositol 1,4,5‐trisphosphate and inositol 1,3,4,5‐tetrakisphosphate. Stimulation of phosphoinositide hydrolysis with noradrenaline produced increases in inositol phosphate production.
Three inositol‐containing phospholipids extracted from resistance arterioles were measured as their glycerol esters following deacylation, thereby permitting an analysis of both membrane and cytosolic components of the phosphoinositide signalling system.
A substantial agonist‐sensitive pool of a previously undescribed inositol but not glycerol‐containing lipid extract component was also identified in this tissue.
These experiments for the first time allow a precise description of phosphoinositide metabolism in resting and agonist‐stimulated resistance arterioles and provide data on a novel compound possibly similar to that recently described in other tissues.