bluuebunny/crossref_metadata_2025_split huggingface dataset:
Haemodynamic and abdominal motor reflexes elicited by neurotensin in anaesthetized guinea‐pigs
Authors: Rioux Francis , Lemieux Margot 
Published: July 2012

Single intraperitoneal (i.p.) injections of neurotensin (NT) (0.14–140 nmol kg−1) in anaesthetized guinea‐pigs were found to trigger transient abdominal wall contractions (TAWC) accompanied by relatively sustained increases of systemic blood pressure (BP) and heart rate (HR). The modification of the latter NT effects by various drugs and surgical manipulations was examined to obtain some insight into the nature of, and possible relationship between, these responses.
The abdominal motor response (i.e. TAWC) to i.p. NT (14 nmol kg−1) was inhibited by prior i.v. injection of the guinea‐pigs with pancuronium (0.27 μmol kg−1), morphine (1.5 and 15 μmol kg−1), clonidine (0.34 μmol kg−1), by concomitant i.p. injection of procaine 2% w/v, or by acute spinalization. It was potentiated by naloxone (2.8 and 28 μmol kg−1), but not affected by i.v. injection of autonomic drugs (i.e. pentolinium, prazosin, yohimbine and atropine), by capsaicin desensitization, or by acute bilateral cervical vagotomy. In spinalized animals a sustained abdominal wall contraction (SAWC) was unmasked, which was resistant to i.v. morphine, clonidine or baclofen but suppressed by i.v. pancuronium or i.p. lignocaine 2% w/v.
Haemodynamic responses to i.p. NT were not affected by i.v. pancuronium, morphine, naloxone, atropine, or by vagotomy. They were inhibited by i.v. pentolinium or clonidine (BP, HR), i.v. prazosin (BP), i.p. procaine 2% w/v (BP, HR), capsaicin desensitization or acute spinalization (BP, HR). Yohimbine (i.v.) potentiated BP and HR increases caused by i.p. NT.
These results suggest that: (1) the haemodynamic and TAWC responses to i.p. NT in this animal model, are two independent, neurally‐mediated reflexes which are likely to originate from the abdominal cavity and require a functionally intact spinal cord for their full expression; (2) the neural pathways subserving both types of responses appear to be different from each other. The nature and time‐response characteristics of the reflexes caused by i.p. NT, raise the possibility that i.p. NT is a noxious stimulus, at least in guinea‐pigs.
Biological activity and metabolism of 20‐hydroxyeicosatetraenoic acid in the human platelet
Authors: Hill Elizabeth , Fitzpatrick Frank , Murphy Robert C. 
Published: July 2012

The cytochrome P‐450 metabolite of arachidonic acid, 20‐hydroxyeicosatetraenoic acid (20‐HETE), was found to be a potent, dose‐dependent inhibitor of platelet aggregation and inhibitor of thromboxane biosynthesis induced by arachidonic acid (IC50 5.2 ± 1.5 μm), A23187 (IC50 16.2 ± 5.4 μm), and U46619 (IC50 7.8 ± 2.4 μm). 20‐HETE did not inhibit thrombin‐induced aggregation.
The human platelet metabolized 20‐HETE to a series of novel metabolites formed by cyclo‐oxygenase as well as lipoxygenase pathways. The structures of the metabolites were identified by mass spectrometry as 20‐hydroxy‐thromboxane B2, 12,17‐dihydroxyheptadecatrienoic acid, 12,20‐dihydroxyeicosatetraenoic acid, and 11,20‐dihydroxyeicosatetraenoic acid.
The identification of the 11‐hydroxy metabolite of 20‐HETE suggests that 20‐HETE is less efficiently cyclized to an endoperoxide intermediate by cyclo‐oxygenase than is arachidonate.
Although some biological activity of 20‐HETE may be related to competition with endogenous arachidonate for cyclo‐oxygenase metabolism, the predominant mechanism of action of 20‐HETE appears to be through antagonism of the prostaglandin H2/thromboxane A2 receptor.
Structure‐activity relations of amiloride and its analogues in blocking the mechanosensitive channel in Xenopus oocytes
Authors: Lane John W. , McBride Don W. , Hamill Owen P. 
Published: July 2012

Patch clamp recording techniques have been used to compare the block caused by amiloride and some of its structural analogues of the mechanosensitive (MS) cation selective channel in frog (Xenopus laevis) oocytes.
Like amiloride, the amiloride analogues dimethylamiloride (DMA), benzamil and bromohexa‐methyleneamiloride (BrHMA) block the MS channel in a highly voltage‐dependent manner.
All analogues tested were more potent blockers than amiloride with IC50's of 500 μm (amiloride), 370 μm (DMA), 95 μm (benzamil) and 34 μm (BrHMA).
Hill plots gave Hill coefficients of 2 (amiloride), 1.8 (DMA), 1 (benzamil) and 1.2 (BrHMA) indicating that the binding of two ligand molecules may be necessary for the block caused by amiloride, DMA and possibly BrHMA whereas only a single ligand molecule may be required for the block by benzamil.
The potential use of BrHMA as a light‐activated, covalent label of the MS channel protein is discussed.
The amiloride analogue ‘fingerprinting’ of the blocking site on the MS channel indicates it is structurally different from previously described amiloride‐sensitive ion transport pathways but may be related to the amiloride binding site on outer hair cells of the ear.
Effects of BRL 38227, sodium nitroprusside and verapamil on collateral perfusion following acute arterial occlusion in the rabbit isolated ear
Authors: Randall Michael D. , Griffith Tudor M. 
Published: July 2012

We have used an isolated, buffer‐perfused, rabbit ear model of acute arterial occlusion to investigate the effects of the nitrovasodilator sodium nitroprusside, the potassium channel activator BRL 38227 (the active (−)‐enantiomer of cromakalim) and the calcium antagonist, verapamil, on collateral perfusion in the absence of pharmacological tone.
Verapamil was the most potent vasodilator (EC50 = 72.6 ± 32.0 nm) of 5‐hydroxytryptamine/histamine‐induced tone in the rabbit isolated perfused ear. Sodium nitroprusside and BRL 38227 were less potent with respective EC50 values of 488 ± 75 nm and 296 ± 40 nm. Following inhibition of endothelium‐derived relaxing factor (EDRF) synthesis, the potency of BRL 38227 was significantly (P < 0.001) increased with an EC50 of 55.6 ± 5.0 nm.
BRL 38227 at 500 nm and 3 μm induced substantial increases in collateral perfusion following arterial ligation in the absence of pharmacological tone compared to control. Furthermore 3 μm BRL 38227 completely reversed the attenuation of collateral perfusion which followed inhibition of EDRF synthesis with 100 μm NG‐nitro‐l‐arginine methyl ester (l‐NAME).
Sodium nitroprusside (500 nm and 3 μm) induced modest improvements in collateral perfusion in the early stages after arterial occlusion.
Verapamil did not influence collateral perfusion at either of the concentrations used (50 nm and 3 μm), even though it was a potent vasodilator.
The results of this study indicate that BRL 38227, and to a much lesser extent sodium nitroprusside, selectively improve collateral perfusion following arterial occlusion, even in the presence of effects of EDRF on acute collateralization, while verapamil has no effect. Furthermore, BRL 38227 also improves collateral perfusion following inhibition of EDRF synthesis. It remains to be established whether BRL 38227 has beneficial actions in acute arterial occlusion in vivo.
Developmental changes in endothelium‐dependent pulmonary vasodilatation in pigs
Authors: Liu S.F. , Hislop A.A. , Haworth S.G. , Barnes P.J. 
Published: July 2012

We compared in vitro endothelium‐dependent vasorelaxant responses to acetylcholine (ACh) and the endothelium‐independent vasodilator response to sodium nitroprusside (SNP) in prostaglandin F2α (PGF2α)‐precontracted muscular pulmonary arteries (PA) from pigs aged 5 min to 2 h (neonatal), 3–10 days, 3–8 weeks and adults.
In the pulmonary artery (PA) rings from neonatal animals, the vasodilator response to ACh was negligible. However, responses to ACh were present in all PA rings from older animals, being greatest at 3–10 days and then decreasing with age (P < 0.001, ANOVA). ACh (30 μm) induced a 1 ± 1%, 92 ± 9%, 62 ± 5% and 51 ± 6% reduction of the PGF2α‐generated tension in neonatal, 3–10 days, 3–8 weeks and adult groups, respectively.
The relaxant response to SNP was present in the PA rings from all age groups and increased with age (P < 0.001, ANOVA). SNP (1 μm)‐induced relaxation was 55 ± 9%, 73 ± 7%, 97 ± 5% and 93 ± 6% in neonatal, 3–10 days, 3–8 week and adult groups, respectively.
Removal of the vascular endothelium abolished the relaxant response to ACh but had no effect on the response to SNP in any groups.
NG‐monomethyl‐l‐arginine (30 μm), a nitric oxide synthesis inhibitor, inhibited the response to ACh but not to SNP. The lipoxygenase inhibitor, nordihydroguaiaretic acid, had no significant effect on responses to ACh or SNP in any group.
These findings suggest that the nitric oxide pathway may not play a part in dilating the pig pulmonary arteries at birth, but may be important during the transitional period of establishing a stable post‐natal pulmonary circulation. The increase in response to SNP with age parallels the increase in smooth muscle cell myofilaments to which it may be related.
Selective and full β1‐adrenoceptor agonist action of a catechol derivative of denopamine (T‐0509) in the guinea‐pig cardiac muscle and trachea: comparison with denopamine, xamoterol and isoprenaline
Authors: Yabana Hideo , Watanabe Hirofumi , Narita Hiroshi , Nagao Taku 
Published: July 2012

The pharmacological actions of T‐0509, a 3‐hydroxy derivative of denopamine, were studied in various guinea‐pig tissues; these effects were compared with those of isoprenaline, denopamine and xamoterol.
The intrinsic activities of the positive inotropic actions of T‐0509, denopamine and xamoterol compared with isoprenaline (= 100%) in the papillary muscle were 99%, 83% and 28%, respectively, while their relative potencies (EC50 agonist EC50 isoprenaline) were 0.23, 33 and 1.4, respectively. The intrinsic activities of T‐0509, denopamine and xamoterol as positive chronotropic agents in the right atria were 98%, 69% and 48%, respectively, and their equipotent concentrations (isoprenaline = 1) were 0.24, 50 and 4, respectively.
The positive chronotropic actions of T‐0509 and denopamine were antagonized by bisoprolol (3 × 10−8 m), but not by ICI 118,551 (3 × 10−8 m).
The intrinsic activity of T‐0509 in histamine‐contracted tracheae was similar to that of isoprenaline, but its equipotent concentration was 38; the effects of both agents were antagonized by ICI 118,551 (3 × 10−8 m), but not by bisoprolol (3 × 10−8 m). Denopamine and xamoterol did not show any agonist activity on guinea‐pig trachea.
Denopamine and xamoterol antagonized the positive chronotropic (pA2, denopamine: 6.98, xamoterol: 7.75) and tracheal relaxant (pA2, denopamine: 5.39, xamoterol: 6.25) effects of isoprenaline.
Isoprenaline, T‐0509 and denopamine, but not xamoterol, contracted the guinea‐pig aorta in a decreasing order in the presence of propranolol (10−6 m).
Based on the above studies, T‐0509 appears to be a highly selective β1‐adrenoceptor agonist with full agonist properties, while denopamine and xamoterol appear to be selective, but partial ft ‐adrenoceptor agonists.
Effects of acute and chronic electroconvulsive shock on noradrenaline release in the rat hippocampus and frontal cortex
Authors: Thomas D.N. , Nutt D.J. , Holman R.B. 
Published: July 2012

Changes in the extracellular content of endogenous noradrenaline (NA) in frontal cortex and hippocampus were determined by in vivo microdialysis following acute and chronic electroconvulsive shock (ECS) in rats anaesthetized with chloral hydrate.
Basal release of NA in the frontal cortex (4.9 ± 0.3 pg/sample) did not differ significantly from that in the hippocampus (4.6 ± 0.2 pg/sample).
A single ECS resulted in an increase of NA release in the hippocampus (21.1 ± 1.3 pg/sample) and in the frontal cortex (11.6 ± 1.2 pg/sample). In both brain regions extracellular NA had returned to basal values within 30 min.
Animals were treated chronically with ECS (once per day for seven days). Twenty‐four h later (day 8), basal release of NA into dialysis samples from the frontal cortex was significantly increased (50%) as compared to chronic sham controls. Basal release in the hippocampus was not significantly different from the sham controls. In the chronic ECS animals the increase in NA released in both brain areas following an ECS on day 8 did not differ from either the chronic sham controls or from animals given acute ECS.
Animals were challenged 24 h after eight ECS or sham control treatments (once per day) with the α2‐adrenoceptor antagonist, idazoxan (10 mg kg−1, s.c). Idazoxan increased NA release in the hippocampus in both groups. There was no difference in the magnitude of the response in ECS‐ and in sham‐treated rats. In the frontal cortex, idazoxan increased the extracellular NA content in the chronic sham controls, but the response to idazoxan was significantly attenuated in the chronic ECS animals.
Chronic but not acute ECS was found to elicit a sustained (> 24 h) increase in the release of NA in the frontal cortex, but not in the hippocampus. The idazoxan data suggest that the increase may be due to a downregulation of presynaptic α2‐adrenoceptors in the frontal cortex. The difference in response of these two brain regions to chronic ECS is discussed in terms of differences in the regulation of extracellular NA content by uptake and autoreceptor activation.
Investigations of the subtype of α2‐adrenoceptor mediating contractions of the human saphenous vein
Authors: Smith Karen , Connaughton Sonia , Docherty James R. 
Published: July 2012

We have examined the effects of a series of α2‐adrenoceptor antagonists against isometric contractions to noradrenaline in human saphenous vein, and correlated these potencies with affinities for the α2A‐ligand binding site of human platelet and the α2B‐ligand binding site of rat kidney.
The α2B‐selective adrenoceptor antagonists, prazosin, ARC 239 and HV 723 showed high, and the α2A‐selective antagonist BRL 44408 showed low, potency in human saphenous vein.
Potency in human saphenous vein correlated better with affinity for the α2B‐ligand binding site (r =0.71, n = 12, P < 0.01) than with affinity for the α2A‐ligand binding site (r = 0.56, n = 12, non significant).
It is concluded that the postjunctional α2‐adenoceptor of human saphenous vein resembles an α2B‐ligand binding site more than an α2A‐ligand binding site.
Differences in evoked dopamine efflux in rat caudate putamen, nucleus accumbens and tuberculum olfactorium in the absence of uptake inhibition: influence of autoreceptors
Authors: Trout Stephen J. , Kruk Zygmunt L. 
Published: July 2012

Dopamine efflux following single pulse or train of pulse stimulations was measured in slices of rat caudate putamen, nucleus accumbens and tuberculum olfactorium, using fast cyclic voltammetry at a carbon fibre microelectrode; 1, 5, 10, 20 or 50 pulses were applied at each location at frequencies varying from 10 Hz to 500 Hz.
There are significant differences in the ability of the different regions to increase dopamine efflux following single or repeated electrical stimulation.
Highest release in response to a single pulse is observed in the caudate putamen (approximately 250 nm dopamine), but the ratio of the peak dopamine overflow following a train of 20 pulses (50 Hz) when compared to a single pulse is rarely greater than three.
Release following single pulse stimulation in the nucleus accumbens (approximately 185 nm dopamine) is often slightly less than in the caudate putamen, but the ratio of peak release when trains of 20 pulses (50 Hz) are compared to single pulse stimulation has been as great as seven fold.
The tuberculum olfactorium releases the least dopamine of the three regions following a single pulse stimulation (approximately 40 nm dopamine), but the ratio of peak dopamine release following trains of 20 pulses (50 Hz) when compared to single pulse can result in a value approaching 20.
When 20 pulses are applied to the caudate putamen at frequencies ranging from 10 to 500 Hz, the peak efflux is essentially the same (frequency/release profile is flat), with the maximum increase only 140% that of a single pulse.
By contrast, in the nucleus accumbens and the tuberculum olfactorium, well defined frequency‐release relationships are seen following 20 pulses applied at 10, 20 and 50 Hz; at higher frequencies the dopamine release decreases as frequency is increased.
Experiments with sulpiride or metoclopramide (dopamine D2 receptor antagonists) indicate that dopamine release in the caudate putamen is not regulated by dopamine autoreceptor activation by endogenous dopamine under our experimental conditions (in the absence of reuptake inhibtion). By contrast, in the nucleus accumbens and in the tuberculum olfactorium, we present evidence to show that at frequencies of stimulation up to 20 Hz, endogenous dopamine acts at dopamine autoreceptors to inhibit further release of dopamine but a minimum exposure time of between 500 and 1000 ms is needed for the response to D2 autoreceptor activation by endogenously released dopamine to be seen.
Localization and characterization of neuropeptide Y binding sites in porcine and human colon
Authors: Walsh David A. , Wharton John , Blake David R. , Polak Julia M. 
Published: July 2012

We have used quantitative receptor autoradiography to investigate the localization and characteristics of binding sites for 125Iodine‐Bolton Hunter‐labelled human neuropeptide Y ([125I]‐BH‐NPY) in porcine and human colon, and compared the binding characteristics with those found in porcine spleen.
Saturable, specific, high affinity [125I]‐BH‐NPY binding was localized to myenteric ganglia in porcine and human colons, and to submucosal ganglia in porcine colon.
Specific [125I]‐BH‐NPY binding to porcine myenteric ganglia was reversible in the presence of guanosine 5′‐O‐(3‐thiotriphosphate) and was inhibited by related peptides with the rank order of potency; porcine NPY = human NPY = peptide tyrosine tyrosine (PYY) ≫ pancreatic polypeptide.
The Y2 selective analogue, NPY(13–36), competed for [125I]‐BH‐NPY binding to porcine myenteric ganglia with greater potency than the Y1 selective analogue, [Leu31, Pro34]NPY, the difference being small, but significant.
The characteristics of [125I]‐BH‐NPY binding to porcine myenteric ganglia were similar to those observed concurrently to porcine splenic red pulp.
The small difference in inhibitory potencies between NPY(13–36) and [Leu31, Pro34]NPY observed in this study in comparison with previous studies was not explained by differential ligand depletion during incubations, but may be due to differences in methodology between binding studies performed on tissue sections and on membranes.
We conclude that specific [25I]‐BH‐NPY binding sites are present in the myenteric and submucosal ganglia of the colon and that these sites may act as functional receptors by which NPY and PYY modulate colonic motility and electrolyte transport.
Stimulation of insulin secretion by imidazoline compounds is not due to interaction with non‐adrenoceptor idazoxan binding sites
Authors: Brown Colin A. , Loweth Anne C. , Smith Stephen A. , Morgan Noel G. 
Published: July 2012

The potency of interaction of several imidazoline compounds with non‐adrenoceptor idazoxan binding sites (NAIBS) in rat liver membranes was compared with their ability to alter insulin secretion from rat pancreatic islets.
NAIBS could be labelled specifically with [3H]‐idazoxan in both rat liver membranes and in rat islet homogenates. Liver binding sites exhibited a KD for [3H]‐idazoxan of 24 nm and a Bmax of 264 fmol mg−1 protein.
Binding of [3H]‐idazoxan to NAIBS in rat liver membranes was displaced effectively by unlabelled idazoxan (IC50 0.1 μm) and by UK14304 (IC50 0.5 μm). However, two other imidazoline compounds efaroxan and RX821002, which are related in structure to idazoxan, were much less effective as displacers.
In insulin secretion experiments, the ATP‐sensitive potassium channel agonist diazoxide (250 μm) was able to suppress the rise in insulin secretion induced by 20 mm glucose. Both efaroxan and RX821002 (100 μm) antagonized the inhibitory effect of diazoxide on glucose‐induced insulin secretion. By contrast, neither idazoxan (100 μm) nor UK14304 (50 μm), was able to overcome significantly the inhibitory effect of diazoxide.
The ability of 100 μm efaroxan to antagonize the suppression of insulin secretion mediated by diazoxide, was not prevented by idazoxan (up to 100 μm) or by UK14304 (up to 50 μm).
The results indicate that the stimulatory effects of imidazoline compounds on insulin secretion are not due to interaction with NAIBS similar to those present in rat liver.
Nitric oxide modulates vascular permeability in the rat coronary circulation
Authors: Filep János G. , Földes‐Filep Éva , Sirois Pierre 
Published: July 2012

The objective of the present study was to assess whether inhibition of nitric oxide (NO) production could modulate vascular permeability in the coronary circulation in conscious rats.
Intravenous injection of NG‐nitro‐l‐arginine methyl ester (l‐NAME, 2 mg kg−1) resulted in a slowly developing hypertension and evoked twofold increases in vascular permeability in the left ventricle and right atrium as measured by the extravasation of Evans blue dye. Maintenance of mean arterial blood pressure at the level observed following l‐NAME injection by infusion of noradrenaline (620–820 ng kg−1 min−1) did not induce significant protein extravasation in the coronary circulation.
l‐NAME treatment markedly enhanced (up to 490%) protein extravasation both in the left ventricle and right atrium in response to platelet‐activating factor (PAF, 1.9 nmol kg−1, i.v.) and endothelin‐1 (1 nmol kg−1, i.v.). Noradrenaline infusion potentiated (up to 69%) endothelin‐1‐induced protein extravasation. The permeability effect of PAF was only slightly enhanced by noradrenaline.
The present findings indicate that inhibition of endogenous NO synthesis leads to an increase in protein extravasation and to potentiation of the permeability effects of PAF and endothelin‐1 in the coronary circulation. These results also suggest that NO may be an important regulator of vascular permeability under physiological and pathological conditions.
Pharmacological differentiation by pertussis toxin of the in vivo acute responses to fMLP and PAF in guinea‐pig lungs
Authors: Arreto C.D. , Bureau M.F. , Imaizumi A. , Vargaftig B.B. 
Published: July 2012

The effects of pertussis toxin on the N‐formyl‐l‐methionyl‐l‐leucyl‐l‐phenylalanine (fMLP) and platelet‐activating factor (PAF)‐induced variations in pulmonary capillary albumin exchanges, blood volume, leucocyte or platelet sequestration were studied in the guinea‐pig, by use of radioactive tracers. The effects of pertussis toxin on pulmonary insuflation pressure were studied in parallel.
The i.v. administration of fMLP and PAF to the guinea‐pig was followed by bronchoconstriction, increased lung capillary albumin exchanges (vasopermeability) sequestration of leucocytes, leucopenia and reduction of blood volume (vasoconstriction). PAF also induced platelet sequestration in lungs and thrombocytopenia.
Pertussis toxin (10 μg kg−1, i.v., 72 h before the experiment) prevented all the studied fMLP‐induced effects, but failed to modify PAF‐induced bronchoconstriction, lung vasoconstriction, platelet sequestration, thrombocytopenia and the increased capillary vasopermeability. In the same conditions the lung leucocyte sequestration was not significantly affected when leucopenia was partially reduced.
It is suggested that the effects of fMLP, but not those of PAF, involve a Gi‐like protein.