bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in mechanical responses of vascular smooth muscles to acetylcholine, noradrenaline and high‐potassium solution in hypercholesterolemic rabbits
Authors: Ibengwe Joshwa K. , Suzuki Hikaru 
Published: July 2012

Mechanical responses produced by high potassium solution (high‐[K]), noradrenaline (NA) and acetylcholine (ACh) were observed in the thoracic aorta and the main pulmonary artery isolated from control and hypercholesterolemic rabbits.
In the hypercholesterolemic rabbit, these tissues showed increased contractile sensitivity to high‐[K], in comparison with those from the control rabbit. In tissues from the control rabbit, mechanical removal of the endothelium did not change the contraction to high‐[K].
The amplitudes of the contractions produced by NA were decreased in tissues from the hypercholesterolemic rabbit, while they were enhanced after removal of the endothelium in tissues from the control rabbit.
The endothelium‐dependent relaxant response to ACh observed in tissues from the control rabbit was diminished, abolished or changed to a contraction in tissues from the hypercholesterolemic rabbit.
It is concluded that in vascular tissues from the rabbit, an increase in contractile sensitivity to high‐[K], a decrease in sensitivity to NA and dysfunction of the endothelium to ACh are induced by feeding a high‐cholesterol diet and these changes in the vascular tissues may thus be involved in the hypertension observed during diet‐induced atherosclerogenesis.
A tachykinin antagonist inhibits gastric emptying and gastrointestinal transit in the rat
Authors: Holzer P. , Holzer‐Petsche U. , Leander S. 
Published: July 2012

The effect of a substance P antagonist, [D‐Pro2, D‐Trp7,9]‐substance P (SPA), on gastric emptying and gastrointestinal transit in the rat was studied in order to elucidate a possible physiological role of endogenous substance P and other tachykinins in gastrointestinal motility. SPA was given by intraperitoneal injection concurrently with the intragastric administration of a test meal containing charcoal and 51Cr.
Examination 15 min after the test meal showed that SPA (0.13‐1.3 μmol kg−1) inhibited gastric emptying and gastrointestinal transit in a dose‐dependent manner.
The inhibitory effect of SPA on gastric emptying and gastrointestinal transit remained unchanged after pretreatment of rats with mepyramine (8.7 μmol kg−1) plus cimetidine (19.8 μmol kg−1) or with guanethidine (67 μmol kg−1).
Since a full examination of SPA as a specific tachykinin antagonist was not possible in vivo, SPA was also tested on circular muscle strips from the rat gastric corpus in vitro. Submaximal contractions in response to bombesin or bethanechol were not reduced by SPA (50 μM), whereas those in response to substance P were inhibited.
The results suggest that SPA inhibits gastric emptying and gastrointestinal transit by interfering with the action of tachykinins released from enteric nerves and that endogenous tachykinins are involved in the regulation of gastrointestinal motility.
Systemic baclofen stimulates gastric motility and secretion via a central action in the rat
Authors: Andrews P.L.R. , Wood K.L. 
Published: July 2012

Intravenous (0.5 mg kg−1) or subcutaneous (2–16 mg kg−1) administration of the γ‐aminobutyric acid (GABA) analogue baclofen resulted in a stimulation of gastric motility and secretion in the rat, anaesthetized with urethane.
The motility response to subcutaneous injection was dose‐related.
This effect was abolished by vagotomy or atropine. There was no response to baclofen in decerebrate animals.
These results indicate that systemic baclofen, probably acting at a site rostral to the brainstem, stimulates gastric motility and acid secretion by a vagally‐dependent mechanism.
Selective inhibition by ethylisopropylamiloride of the positive inotropic effect evoked by low concentrations of ouabain in rat isolated ventricles
Authors: Finet Michel , Godfraind Théophile 
Published: July 2012

The biphasic positive inotropic effect of ouabain has been studied in rat ventricular strips in the presence of ethylisopropylamiloride (EIPA) an inhibitor of Na+/H+ exchange.
EIPA (10–20 μM) depressed dose‐dependently the high affinity component of the ouabain inotropic effect, whereas it did not significantly modify the low affinity inotropic effect related to high concentrations of ouabain.
At the EIPA concentrations studied, there was no observable modification of the inotropic effect of Bay K 8644 (10 nM, 0.3 μM) or of isoprenaline (10 nM, 1 μM).
These results indicate that the inotropic effect of ouabain resulting from its interaction with high affinity sites is selectively sensitive to EIPA.
On the mechanisms of k‐opioid‐induced diuresis
Authors: Blackburn T.P. , Borkowski K.R. , Friend J. , Rance M.J. 
Published: July 2012

In conscious saline loaded rats, the k‐opioid agonists tifluadom, U50488, and ethylketocyclazocine, given subcutaneously, induced a characteristic diuresis which could be antagonized by naloxone.
Bilateral adrenal demedullation significantly reduced adrenal gland catecholamine content and plasma adrenaline levels, but did not significantly affect plasma corticosterone levels, indicating that the adrenal cortex remained both intact and functional.
Seven days following bilateral adrenal demedullation, the subcutaneous administration of the k‐agonists no longer induced diuresis. However, demedullation did not affect the diuretic response to frusemide or clonidine, nor did it affect the antidiuretic response induced by the μ‐opioid agonists morphine and buprenorphine.
Adrenal catecholamines do not appear to be involved in k‐opioid‐induced diuresis, since pretreatment with propranolol, prazosin and idazoxan did not affect the diuretic response in intact animals.
The results indicate a link between the adrenal medulla and k‐opioid‐induced diuresis and suggest that a peripheral mechanism may also be involved in mediating this effect.
Renal effects of gastrin C‐terminal tetrapeptide (as pentagastrin) and cholecystokinin octapeptide in conscious rabbit and man
Authors: Calam J. , Gordon D. , Peart W.S. , Taylor S.A. , Unwin R.J. 
Published: July 2012

Pentagastrin and cholecystokinin octapeptide (CCK8) were infused i.v. at three different doses in two sets of 4 conscious rabbits following a repeated measurements design (130, 1,300 and 13,000 pmol kg−1 min−1 pentagastrin; 5, 50 and 450 pmol kg−1 min−1 CCK8). In man, two different doses of pentagastrin (13 and 65 pmol kg−1 min−1) were infused in two groups of 6 subjects, and CCK8 (2 pmol kg−1 min−1) in a third group. According to published human postprandial levels, plasma CCK8‐like immunoreactivity concentrations were supraphysiological at all doses infused.
In the rabbit, pentagastrin produced a dose‐related fall in urine flow and free water clearance, but no significant change in systemic and renal haemodynamics, electrolyte excretion and measured plasma constituents; however, in human subjects, pentagastrin increased renal sodium excretion and reduced potassium excretion but did not change glomerular filtration rate.
In the rabbit, CCK8 produced a dose‐related fall in plasma renin activity, plasma calcium concentration and mean arterial blood pressure; dose‐dependent increases in effective renal plasma flow, glomerular filtration rate and renal sodium excretion. In man, changes in sodium and potassium excretion similar to pentagastrin were observed; there were no significant changes in plasma renin activity, plasma calcium concentration, blood pressure, effective renal plasma flow or glomerular filtration rate.
The pharmacological renal effects of pentagastrin in conscious water‐loaded rabbits resemble vasopressin. In contrast, CCK8′s most striking effect was vasodilatation and was unusual in inhibiting rather than stimulating renin release. In man the net changes in urine composition found during infusion of these peptides are similar to those produced by the potassium‐sparing diuretics, amiloride and triamterene. However the generally weak renal effects observed, even at pharmacological doses, indicate that these peptides are unlikely to influence renal function under normal physiological conditions.
An investigation of the role of adrenergic innervation in the regulation of the extraneuronal uptake of [3H]‐isoprenaline into rat vasa deferentia and atria
Authors: Morton A.J. 
Published: July 2012

Destruction of adrenergic nerves by neonatal guanethidine treatment did not affect the extraneuronal accumulation of [3H]‐isoprenaline by adult vasa deferentia or atria.
Neither pre‐nor post‐ganglionic denervation of vasa deferentia resulted in a significant change in extraneuronal accumulation of [3H]‐isoprenaline.
The appearance and subsequent development of extraneuronal uptake in embryonic and newborn rats did not appear to be dependent on a fully developed or functional adrenergic innervation.
Decreasing plasma catecholamine levels by adrenal demedullation did not have an effect on extraneuronal uptake.
Chronic cold exposure (7 days) significantly increased plasma levels of adrenaline, and there was a significant decrease in the corticosterone‐sensitive extraneuronal uptake of [3H]‐isoprenaline into atria. After 14 days in the cold, plasma adrenaline levels had fallen, and were no longer significantly different from control levels.
The extraneuronal uptake of [3H]‐isoprenaline into atria after 14 days cold exposure was no longer different from that of control atria. There did not appear to be a direct correlation between plasma catecholamines and extraneuronal accumulation of [3H]‐isoprenaline.
Neither the presence of adrenergic nerves nor plasma catecholamines appear to play a major role in the regulation of extraneuronal uptake by atria and vasa deferentia of the rat.
Effects of sympathetic stimulation and applied catecholamines on mechanical and electrical responses to stimulation of the vagus nerve in guinea‐pig isolated trachea
Authors: McCaig Dorothy J. 
Published: July 2012

Mechanical and electrical responses to stimulation of the vagus nerve were studied in the isolated, innervated trachea of the guinea‐pig.
In approximately half the preparations tested, the amplitudes of mechanical constrictor responses to stimulation of the vagus were reduced substantially during a period of sympathetic stimulation. Vagal responses were unaltered in the remainder.
In single trachealis cells, stimulation of the vagus nerve or sympathetic stellate ganglion elicited depolarization and hyperpolarization, respectively. Vagally‐mediated depolarization was decreased, unchanged or increased in amplitude after a period of sympathetic stimulation.
Isoprenaline almost abolished mechanical responses induced by stimulation of the vagus, and this effect was blocked by propranolol.
Noradrenaline attenuated markedly vagal mechanical responses also, and this effect was blocked by a combination of propranolol and phentolamine.
Both noradrenaline and isoprenaline hyperpolarized single trachealis cells and greatly reduced the amplitude of vagally‐mediated depolarization.
Neither sympathetic stimulation nor applied catecholamines altered mechanical responses to applied acetylcholine, strongly suggesting that their effects on vagal responses are predominantly presynaptic.
Differing electrophysiological effects of class IA, IB and IC antiarrhythmic drugs on guinea‐pig sinoatrial node
Authors: Campbell Terence 
Published: July 2012

Standard microelectrode techniques were used to study the effects of class IA (quinidine, disopyramide, procainamide), IB (lignocaine, mexiletine, tocainide) and IC (flecainide, encainide, lorcainide) antiarrhythmic drugs on action potentials in spontaneously beating sino‐atrial node cells from guinea‐pigs.
The IA drugs all produced significant slowing of spontaneous rate in therapeutic concentrations. The IB agents did so only in concentrations well above therapeutic levels and the IC drugs were of intermediate potency.
All nine drugs markedly slowed the repolarization rate and this was the major mechanism of sinus slowing for the IA and IC compounds. The IB drugs shared this effect but prolongation of phase 4 by reduction of the slope of diastolic depolarization was also a prominent feature of their action.
The novel anticonvulsant MK‐801 binds to the activated state of the N‐methyl‐d‐aspartate receptor in rat brain
Authors: Foster Alan C. , Wong Erik H.F. 
Published: July 2012

The influence of endogenous and exogenous acidic amino acids on the binding of [3H]‐MK‐801, a selective, non‐competitive antagonist of N‐methyl‐d‐aspartate (NMDA) receptors, has been investigated in rat cerebral cortex crude synaptic membranes (CSM).
Removal of endogenous glutamate and aspartate from CSM by repeated washing reduced the affinity of [3H]‐MK‐801 for its binding site (with no change in the total number of binding sites) and increased NMDA‐sensitive l‐[3H]‐glutamate binding.
In washed CSM, competitive NMDA antagonists of the dl‐α‐amino‐ω‐phosphonocarboxylate series reduced [3H]‐MK‐801 binding and NMDA‐sensitive L‐[3H]‐glutamate binding, the most active compounds being 2‐amino‐5‐phosphonovalerate (AP5) and 2‐amino‐7‐phosphono‐heptanoate (AP7).
Exogenous excitatory amino acid agonists enhanced the binding of [3H]‐MK‐801 to washed CSM by up to 700%. A selective involvement of NMDA receptors in these effects was indicated by the excellent correlation between EC50s for stimulation of [3H]‐MK‐801 binding and IC50s for inhibition of NMDA‐sensitive l‐[3H]‐glutamate binding in the same membranes.
The selective, competitive NMDA receptor antagonist D‐AP5 blocked the l‐glutamate‐induced increase in [3H]‐MK‐801 binding in a competitive manner with a pA2 value of 6.0.
These results seem to reflect a molecular interaction between two distinct components of the NMDA receptor complex: the transmitter recognition site and the site through which MK‐801 exerts its antagonist effects, possibly the ion channel.
Effects of cations on binding, in membrane suspensions, of various opioids at μ‐sites of rabbit cerebellum and κ‐sites of guinea‐pig cerebellum
Authors: Kosterlitz H.W. , Paterson S.J. , Robson L.E. , Traynor J.R. 
Published: July 2012

At the μ‐sites of rabbit cerebellum, NaC1, LiC1, KCl, choline chloride and MnCl2 were tested for potentiation and inhibition of the binding of several opioids. Naloxone, (–)‐bremazocine and diprenorphine are μ‐antagonists in pharmacological assays and their binding is potentiated by the lower concentrations and inhibited by the higher concentrations of NaCl. The binding of the agonists [3H]‐[d‐Ala2, MePhe4, Gly‐ol5]enkephalin and [3H]‐dihydromorphine is inhibited. MnCl2/potentiates the binding of the agonist [3H]‐[d‐Ala2, MePhe4, Gly‐ol5]enkephalin but not the binding of the antagonists. The thresholds of inhibition and slopes of the dose‐response curves for inhibition by MnCl2 and LiCl vary. This finding may indicate that potentiating effects of MnCl2 and LiCl are masked by simultaneous inhibition.
At the κ‐sites of guinea‐pig cerebellum, NaCl, KCl and MnCl2 inhibit the binding of [3H]‐dynorphin A (1–8), [3H]‐dynorphin A (1–9), [3H]‐(–)‐bremazocine, [3H]‐tifluadom, and [3H]‐diprenorphine. NaCl also causes a small potentiation of the binding of [3H]‐diprenorphine, which is a κ‐agonist in the guinea‐pig myenteric plexus but a κ‐antagonist in the rabbit vas deferens. The slopes of the inhibitory dose‐response curves and the thresholds of inhibition vary with the different ligands. Therefore some potentiating effects may have been masked.
The results support the view that NaCl, and perhaps LiCl, but not KCl and choline chloride, potentiate the binding of μ‐antagonists but not the binding of μ‐agonists. It is not yet possible to decide whether, at the κ‐site, there is a similar differentiation of the binding of agonists and antagonists.
Increase in acetylcholine concentrations in the brain of ‘old’ rats following treatment with pyrithioxin (Encephabol)
Authors: Martin K.J. , Vyas S. 
Published: July 2012

Treatment of old rats, for two to three weeks, with pyrithioxin led to an increase in the levels of endogenous acetylcholine (ACh) in the cortex and the striatum but not in the hippocampus.
Pretreatment of old rats with pyrithioxin also increased the resting release and the K+‐stimulated release of radioactive ACh from brain slices in vitro.
Adamantane derivatives: a new class of insulin secretagogues
Authors: Garrino M.G. , Henquin J.C. 
Published: July 2012

Adamantane derivatives were found to increase insulin release in vitro. Mouse islets were used to study the mechanisms and molecular requirements of that hitherto unrecognised property.
At a non‐stimulatory concentration of glucose (3 mm), 1‐adamantanamine (1 mm) reversibly inhibited 86Rb efflux from islet cells, depolarized the β‐cell membrane, induced electrical activity, stimulated 45Ca uptake and efflux, and triggered insulin release. Omission of extracellular Ca2+ abolished the secretory response but only partially inhibited the acceleration of 45Ca efflux.
At a stimulatory concentration of glucose (10 mm), 1‐adamantanamine reversibly increased 86Rb efflux, potentiated electrical activity (lengthening of the slow waves with spikes), augmented 45Ca uptake and efflux, and increased insulin release. The effects of adamantanamine were dose‐dependent, with a threshold concentration of 10 μm for stimulation of release.
2‐Adamantanamine was as potent as 1‐adamantanamine. In contrast, substitution of the amino group by a carboxyl group (1‐adamantanecarboxylic acid) decreased the effectiveness by about 65%, and substitution by a hydroxyl group (1‐adamantanol) suppressed it.
It is concluded that adamantane derivatives bearing an amino group decrease K+ permeability of the β‐cell membrane and thereby cause depolarization. This activates voltage‐dependent Ca channels, permits Ca2+ influx and eventually stimulates insulin release. They may also mobilize cellular Ca2+, but this effect is not sufficient to cause release.
Tyr‐MIF‐1 attenuates antinociceptive responses induced by three models of stress‐analgesia
Authors: Galina Z. Harry , Kastin Abba J. 
Published: July 2012

Tyr‐MIF‐1 (Tyr‐Pro‐Leu‐Gly‐NH2), a biologically active brain peptide, has previously been shown to antagonize the analgesia induced by morphine.
In this report experiments are described in which mice were tested on the hot‐plate in three models of antinociception—shock, novel environment, and warm‐water swim—after the administration of various doses of Tyr‐MIF‐1 without any exogenous opiates.
The peptide reduced the antinociception produced by all three methods of inducing endogenous antinociception.
These results add further support for the existence of peptides like Tyr‐MIF‐1 that act as opiate antagonists.
The effect of platelet activating factor on pulmonary β‐adrenoceptors
Authors: Barnes P.J. , Grandordy B.M. , Page C.P. , Rhoden K.J. , Robertson D.N. 
Published: July 2012

An intravenous infusion of platelet activating factor (Paf) in the guinea‐pig elicits an increase in bronchial responsiveness to the spasmogens, histamine and bombesin.
Airways obstruction induced by bombesin in Paf‐treated animals is poorly reversed by isoprenaline compared to comparable airways obstruction induced by bombesin in vehicle‐treated animals.
Isoprenaline induced a comparable dose‐related relaxation in vitro of tracheal smooth muscle isolated from Paf‐ and vehicle‐treated animals.
No change in β‐adrenoceptor numbers or binding affinity was observed in lungs removed from Paf‐treated animals in comparison with those from vehicle‐treated animals, or after direct incubation with Paf in vitro.
The reduced bronchodilator responsiveness to isoprenaline in Paf‐treated animals is not related to changes in pulmonary β‐adrenoceptor function. These results suggest that non‐spasmogenic elements may contribute to airways obstruction induced in hyper‐responsive animals.
Evaluation of a new and potent cholecystokinin antagonist on motor responses of the guinea‐pig intestine
Authors: Barthó Loránd , Holzer Peter , Lembeck Fred , Lippe Irmgard Th. , Setnikar Ivo 
Published: July 2012

The potency and selectivity of d,l‐4‐(3,4‐dichloro‐benzoyl‐amino)‐5‐(dipentyl‐amino)‐5‐oxo‐pentanoic acid (CR 1409) as a cholecystokinin (CCK) antagonist was investigated on motor responses of the longitudinal and circular muscles of the guinea‐pig isolated ileum. CR 1409 was further used to examine whether nerve‐mediated motor responses to electrical field stimulation or distension of the gut wall may involve the release of CCK‐like peptides
CR 1409 (0.06‐2.1 μm) antagonized longitudinal muscle responses to ceruletide (caerulein, a CCK‐related decapeptide) in a concentration dependent and competitive manner (pA2 7.77); responses to CCK‐octapeptide (CCK‐8) were antagonized with a similar potency. Contractions of the circular muscle evoked by ceruletide were also blocked by CR 1409 (0.2‐0.4 μm).
Longitudinal muscle contractions in response to dimethylphenylpiperazinium, bethanechol, histamine, substance P, or 5‐hydroxytryptamine (5‐HT), and circular muscle contractions evoked by acetylcholine, 5‐HT, substance P, or substance K were not altered by CR 1409 (0.4 μm). Longitudinal muscle contractions induced by electrical field stimulation (with pulses delivered at 0.05 and 1 Hz in the absence, and at 5 Hz in the presence of atropine) were not or only slightly reduced by CR 1409 (0.4 μm). Longitudinal contractions due to activation of extrinsic nerves by capsaicin remained unaltered in the presence of CR 1409 (0.4 μm).
Reflex contractions of the circular muscle, induced by balloon distension and recorded orally to the site of distension, and peristaltic activity elicited by intraluminal infusion of Tyrode solution remained unaffected by CR 1409 (0.4 μm).
These findings indicate that CR 1409 is a potent and selective antagonist of CCK‐like peptides in the guinea‐pig ileum. The results do not provide any evidence that CCK‐like peptides, released from extrinsic or intrinsic neurones, are involved in nerve‐mediated contractions of intestinal muscle and in the peristaltic reflex.