bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced coronary vasoconstrictor responses to 5‐hydroxytryptamine in the presence of a coronary artery stenosis in anaesthetized dogs
Authors: Woodman Owen L. 
Published: July 2012

In the anaesthetized dog, left circumflex coronary artery blood flow and external diameter were measured and the vascular responses to an injection of 5‐hydroxytryptamine (5‐HT, 0.02–2 μg kg−1) assessed, before and after a screw clamp had been placed on the artery to produce a severe stenosis.
In the normal coronary circulation, intra‐coronary (i.c.) injection of 5‐HT increased coronary blood flow (CBF) but decreased the external diameter of the large coronary artery (CD), without affecting systemic mean arterial pressure or heart rate.
In the normal coronary circulation, the 5‐HT‐induced increases in CBF were unaffected by blockade of 5‐HT2‐receptors with ketanserin (0.1 mg kg−1 i.c.) but were significantly attenuated by blockade of 5‐HT1‐like receptors with methysergide (0.1 mg kg−1 i.c.).
In the presence of a severe stenosis, the increase in CBF produced by 5‐HT was markedly attenuated and a secondary decrease in CBF was revealed. The stenosis also caused a marked enhancement of the 5‐HT‐induced constriction of the large artery, such that the reduction of the CD was approximately doubled at all doses of 5‐HT tested. The enhanced 5‐HT‐induced reduction in CD was similar with placement of the stenosis either proximal or distal to the site of diameter measurement.
In the presence of the stenosis, blockade of 5‐HT2‐receptors with ketanserin (0.1 mg kg−1 i.c.) significantly attenuated the 5‐HT‐induced decreases in CD and CBF.
These results demonstrate that, in the anaesthetized dog, placement of a severe, flow‐limiting stenosis enhances 5‐HT‐induced constriction of the large coronary arteries and reveals a reduction in coronary blood flow. These observations support suggestions that, in the presence of coronary artery disease, 5‐HT could contribute to reductions in coronary blood flow leading to myocardial ischaemia.
Contractile activity of three endothelins (ET‐1, ET‐2 and ET‐3) on the human isolated bronchus
Authors: Advenier C. , Sarria B. , Naline E. , Puybasset L. , Lagente V. 
Published: July 2012

The effects of three endothelins: (i) the classical or human/porcine endothelin (ET‐1); (ii) [Trp6, Leu7] endothelin (ET‐2) and (iii) [Thr2, Phe4, Thr5, Tyr6, Lys7, Tyr14] endothelin or rat endothelin (ET‐3) were tested on the human isolated bronchus.
ET‐1 produced a concentration‐dependent contraction of the human isolated bronchus that proceeded in two different steps. The first step was observed at very low concentrations (pD2 = 11.01 ± 0.17, n = 10) but corresponded to a low intrinsic activity (Emax = 15.6 ± 1.8% of Emax induced by acetylcholine (ACh) 3 × 10−3 m, n = 10). This effect was potentiated by Bay K 8644 10−7 m (Emax = 26.1 ± 2.9% of ACh 3 × 10−3 m, n = 5, P < 0.05), reduced by nicardipine 10−6 m (Emax = 6.0 ± 2.6% of ACh 3 × 10−3 m, n = 5, P < 0.05) and strongly inhibited in calcium‐free medium. The second step of the action of ET‐1 corresponded to a lesser potency (pD2 = 7.90 ± 0.17, n = 9) but a higher intrinsic activity (Emax = 82.5 ± 4.7% of ACh 3 × 10−3 m). This effect was not significantly modified by nicardipine 10−6 m or by Bay K 8644 10−7 m. Neither of the two effects was modified by indomethacin 3 × 10−6m.
The effects of ET‐2 and ET‐3 were qualitatively similar to those of ET‐1 but quantitatively different; for these two steps of contracting activity and for potency and efficacy the ranking was: ET‐1 > ET‐2 = ET‐3.
Thus, ET‐1 appears to be the most potent of these three substances in its effect on the human isolated bronchus. Its activity seems to involve the action of voltage‐dependent calcium channels at low concentrations (10−12 to 10−9 m), whereas other mechanisms are involved at higher concentrations (10−8 to 3 × 10−7 m).
Evidence that an atypical β‐adrenoceptor mediates the inhibition of spontaneous rhythmical contractions of rabbit isolated jejunum induced by ritodrine and salbutamol
Authors: Norman Bernard J. , Leathard Helen L. 
Published: July 2012

The nature of the adrenoceptors mediating the inhibitory action of noradrenaline, ritodrine and salbutamol on the spontaneous activity of longitudinal muscle of the rabbit jejunum in vitro was investigated by use of a range of adrenoceptor antagonists.
The actions of ritodrine and salbutamol were antagonized competitively by propranolol. The pA2 values of 6.4 and 6.6 respectively were smaller than those found elsewhere for β1‐ and β2‐adrenoceptors.
In contrast, the responses to ritodrine and salbutamol were antagonized only by high concentrations (>2.7 μm) of phentolamine and were unaffected by yohimbine (2.6 μm), mepyramine (2.5 μm) or cimetidine (4.0 μm).
Ritodrine which is less potent than salbutamol in tissues with typical β2‐adrenoceptors was found to be 8 times more potent than salbutamol in the rabbit jejunum.
It is suggested that in the rabbit jejunum ritodrine and salbutamol may act at an atypical β‐adrenoceptor, at which propranolol is a competitive but not very potent antagonist.
PAF‐induced bronchial hyperresponsiveness in the rabbit: contribution of platelets and airway smooth muscle
Authors: Coyle A.J. , Spina D. , Page C.P. 
Published: July 2012

Aerosol administration of platelet activating factor (PAF) to normal rabbits induced an enhanced airway responsiveness to inhaled histamine, 6 and 24 h after exposure. Following exposure to bovine serum albumin (BSA) as the carrier molecule for PAF, there was an increase in airway responsiveness to histamine 6h after challenge, although by 24 h this was not significantly different from the responsiveness of airways to histamine before BSA.
PAF‐induced bronchial hyperresponsiveness at 24 h was associated with a substantial increase in the number of neutrophils and mononuclear cells and a small, but significant increase in the number of eosinophils in the lungs as assessed by bronchoalveolar lavage. BSA exposure failed to alter the total number of cells in the lungs, although there was a significant increase in the number of neutrophils in the bronchoalveolar lavage fluid.
Selective platelet depletion with a guinea‐pig anti‐rabbit platelet serum inhibited PAF‐induced bronchial hyperresponsiveness. In addition, there was an attenuation of PAF‐induced airway inflammation in animals rendered thrombocytopenic.
The contractile potency to histamine, methacholine and carbachol was similar in intrapulmonary bronchi taken from rabbits exposed to an aerosol of BSA or PAF. Furthermore, the relaxant potency to the non‐selective β‐adrenoceptor agonist isoprenaline, was unaltered in PAF‐treated rabbits. In contrast, there was a 2.58 fold reduction in the relaxant potency to theophylline in rabbits exposed to PAF compared with rabbits exposed to BSA.
These results suggest that in the rabbit, PAF‐induced bronchial hyperresponsiveness at 24 h is associated with airways inflammation and is dependent upon platelet activation, but is not related to changes in airway smooth muscle function.
Investigation into atropine‐induced antinociception
Authors: Ghelardini C. , Malmberg‐Aiello P. , Giotti A. , Malcangio M. , Bartolini A. 
Published: July 2012

The effect of atropine on the nociceptive system was examined in mice and rats by use of the hot‐plate, writhing and tail‐flick tests.
Atropine dose‐dependently produced analgesia, no effect and hyperalgesia. Analgesia was observed in both species with doses ranging from 1 to 100 μg kg−1 while hyperalgesia was obtained with 5 mg kg−1.
Atropine antinociception was prevented by pirenzepine (0.1 μg per mouse, i.c.v.), dicyclomine (10 mg kg−1, i.p.), atropine‐methylbromide (0.5 μg per mouse, i.c.v.) and hemicholinium‐3 (1 μg per mouse, i.c.v.). Naloxone (1 mg kg−1, i.p.), α‐methyl‐p‐tyrosine (100 mg kg−1, s.c.) and reserpine (2 mg kg−1, i.p.) were ineffective.
The site of atropine analgesia is in the CNS since it exerts its antinociceptive effect also when injected i.c.v. (1–10 ng per mouse). Moreover drugs which do not cross the blood‐brain barrier, such as hemicholinium‐3, pirenzepine and atropine methylbromide, were unable to antagonize atropine analgesia if administered i.p.
Atropine also in vitro, showed a biphasic action on electrically‐evoked guinea‐pig ileum contractions. Concentrations between 10−14 and 10−12m increased electrically and nicotine‐evoked contractions but did not affect acetylcholine‐ and oxotremorine‐evoked contractions. Concentrations above 10−9m inhibited both electrically‐ and drug (acetylcholine, nicotine and oxotremorine)‐evoked contractions while they were ineffective on unstimulated ileum.
On the basis of the above findings, amplification of cholinergic transmission by very low doses of atropine is postulated, through a selective blockade of presynaptic muscarinic autoreceptors, as the likely mechanism of action.
Atropine antinociception, unlike oxotremorine antinociception, was obtained without any impairment of mouse rota‐rod performance.
The antagonism by pirenzepine and dicyclomine of oxotremorine and atropine antinociception suggests that M1 muscarinic receptor subtypes are responsible for cholinergic analgesia.
Actions of 5‐HT1 ligands on excitatory synaptic transmission in the hippocampus of alert rats
Authors: O'Connor J.J. , Rowan M.J. , Anwyl R. 
Published: July 2012

The effects of 5‐hydroxytryptamine1 (5‐HT1) ligands on excitatory synaptic transmission were examined in the stratum radiatum of the CA1 region of the dorsal hippocampus of alert, gently restrained, rats.
5‐HT produced a dose‐dependent reduction in the amplitude of the electrically evoked population excitatory postsynaptic potential (e.p.s.p.) when injected directly into the hippocampus via a cannula (dose producing 50% maximum inhibition, ED50 = 0.46 μg).
Direct intrahippocampal (i.h.) application of buspirone (ED50 = 0.29 μg), gepirone (1 μg), ipsapirone (1 μg), BMY 7378 (0.1 μg) and 5‐carboxamidotryptamine (5‐CT, 0.02 μg) mimicked the inhibitory effect of 5‐HT.
Systemic injection of buspirone (ED50 = 0.88 mg kg−1, i.p.), BMY 7378 (0.01 mg kg−1, i.p.) and RU 24969 (1 mg kg−1 s.c.) also had an inhibitory effect on the amplitude of the e.p.s.p.
Injection of 8‐hydroxy‐2‐(di‐n‐propylamino) tetralin (8‐OH‐DPAT, 2 μg) and spiroxatrine (1 μg) i.h. alone had no effect on the e.p.s.p. amplitude but prevented the inhibitory effect of 5‐HT.
Systemic injection (i.p.) of methysergide (5 mg kg−1) and spiroxatrine (1mg kg−1) antagonized the inhibitory effect of buspirone whereas pretreatment with ketanserin (1mg kg−1), trifluoperazine (1 mg kg−l) and idazoxan (1 mg kg−l) had no effect on the response to buspirone.
It is concluded that hippocampal synaptic transmission is highly sensitive to the agonist and antagonist properties of 5‐HT1 ligands in the alert rat.
Effects of pre‐contraction with endothelin‐1 on α2‐adrenoceptor‐and (endothelium‐dependent) neuropeptide Y‐mediated contractions in the isolated vascular bed of the rat tail
Authors: MacLean Margaret R. , McGrath J. C. 
Published: July 2012

The pressor effects to bolus doses of the α2‐adrenoceptor agonist UK‐14,304 were studied in the isolated vascular bed of the perfused rat tail before and after increasing the perfusion pressure with infusions of endothelin‐1. Those of neuropeptide Y were studied before and after pre‐constriction with endothelin‐1 or 5‐hydroxytryptamine. The pressor effects of neuropeptide Y were studied before and after functional disruption of the endothelium with the detergent CHAPS.
Endothelin‐1 and the α1‐adrenoceptor agonist phenylephrine induced dose‐dependent vasoconstriction, endothelin‐1 being some 104 times more potent than phenylephrine [log dose (mol) of the ED50 for endothelin‐1 and phenylephrine: −11.8 ± 0.2 (n = 7), −8.2 ± 0.2 (n = 5) respectively].
Under control conditions, at basal perfusion pressures, UK‐14,304 and neuropeptide Y were virtually inactive as vasoconstrictors. Following a sustained increase in perfusion pressure by infusions of endothelin‐1 (2.5–10 nM at 0.8 ml min−1), however, both UK‐14,304 and neuropeptide Y induced dose‐dependent pressor responses and both were some 102 times more potent than phenylephrine [log dose (mol) of the ED50 for UK‐14304 and neuropeptide Y: −10 ± 0.5 (n = 6), −10.3 ± 0.4 (n = 6) respectively]. Responses to neuropeptide Y also were uncovered when vascular tone was increased with 5‐hydroxytryptamine (5–20 nm) [log dose (mol) of the ED50 for neuropeptide Y: −10.2 ± 0.2 (n = 6)].
Pre‐constriction‐induced pressor responses to UK‐14,304 were inhibited by 1 μm rauwolscine whilst those to neuropeptide Y were inhibited by disruption of the endothelium. Removal of the endothelium had no significant effect on the pressor responses to 4 pmol or 8 pmol endothelin‐1 and had no effect on the increase in perfusion pressure induced by the endothelin‐1 infusions but did decrease the time‐course of pressor responses to bolus injections of endothelin‐1. Endothelial disruption had no significant effect on the vasoconstriction induced by all but one of the doses of phenylephrine administered [log dose (mol) of the ED50 for phenylephrine after CHAPS: −8.6 ± 0.2 (n = 5)], indicating that the responsiveness of the vascular smooth muscle was not destroyed by CHAPS. This treatment did, however, slow the onset and prolong the time course of the phenylephrine‐induced responses.
These results indicate that, in the isolated vascular bed of the rat tail, pressor responses to both α2‐adrenoceptor‐ and neuropeptide Y receptor‐activation are uncovered by agonist‐induced preconstriction including that to endothelin‐1. Neuropeptide Y‐induced vasoconstriction was endothelium‐dependent.
Evidence for the presynaptic action of 5‐hydroxytryptamine and the involvement of purinergic innervation in the rabbit lower urinary tract
Authors: Chen Hong‐I 
Published: July 2012

The effects of 5‐hydroxytryptamine (5‐HT) were studied in vitro on bladder and urethral muscle strips from the rabbit. 5‐HT produced dose‐dependent contraction in the detrusor and urethra.
The 5‐HT‐induced contraction could be dose‐dependently inhibited by the 5‐HT3 antagonists MDL 72222, ICS 205–930 and BRL 43694. No effect of ketanserin, methysergide or metitepine was observed on the contractile response to 5‐HT.
Atropine and α,β‐methylene ATP both partially blocked the contractile response to 5‐HT. Together they caused more inhibition than either alone.
Atropine and α,β‐methylene ATP also inhibited the contractile response to electrical field stimulation. The 5‐HT3 antagonist MDL 72222 had no effect on the contraction to field stimulation.
The atropine‐ and α,β‐methylene ATP‐resistant components of 5‐HT‐induced contraction were not affected by the 5‐HT1 antagonists metitepine, the 5‐HT2 antagonists ketanserin and methysergide or the 5‐HT3 antagonists MDL 72222, ICS 205–930 and BRL 43694.
Tetrodotoxin, hexamethonium, phentolamine and prazosin had no effect on the contractile response to 5‐HT.
These results suggest that in the rabbit lower urinary tract (i) there are 5‐HT3 receptors, (ii) the contractile response to 5‐HT is mediated by presynaptic stimulation, (iii) there is non‐adrenergic, non‐cholinergic excitatory neurotransmission.
General anaesthetics and field currents in unclamped, unmyelinated axons of rat olfactory cortex
Authors: McGivern J. , Scholfield C.N. 
Published: July 2012

The effects of seven general anaesthetics and one local anaesthetic having a wide range of physical and chemical properties were studied on nerve terminal Na‐ and K‐mediated currents in slices of olfactory cortex. These currents were measured from the groups of fine unmyelinated axons traversing the surface of the olfactory cortex and which give off synapses en passant. The amplitude of the K‐current was visualized by depolarizing the axons via an electrode polarization.
The anaesthetics tested were ketamine (0.1–2 mm), pentobarbitone (0.1–5 mm), urethane (5–200 mm), halothane (0.5–5 mm), ether (10–200 mm), alphaxalone (0.001–0.05 mm), diisopropylphenol (0.05–0.5 mm) and lignocaine (0.01–0.5 mm). All had depressant effects on the axonal Na‐current (at the higher concentrations tested) and on the K‐current (at slightly lower concentrations). The apparent lower potency on the Na‐current was considered to be due to a masking of effect as a consequence of the reduction in the K‐mediated membrane rectification rather than any real difference in the susceptibilities of the Na and K‐currents.
Some of the depressant effect of pentobarbitone and alphaxalone was γ‐aminobutyric acid (GABA)‐mediated as indicated by the reduced potency in the presence of bicuculline. The actions of ketamine and halothane were unaffected by bicuculline.
For some anaesthetics these axonal depressant effects might contribute to general anaesthesia, while for other substances the relatively high concentrations necessary would suggest that this mode of action does not produce effective anaesthesia in vivo.
Effects of galanin, its analogues and fragments on rat isolated fundus strips
Authors: Katsoulis Stavros , Schmidt Wolfgang E. , Schwörer Harald , Creutzfeldt Werner 
Published: July 2012

Rat and porcine galanin (rGal and pGal) produced dose‐dependent contraction of rat fundus strips in a concentration range of 6 nm–100 nm.
The stimulatory effect of rGal on rat fundus strips was not modified in the presence of somatostatin (250 nm), naloxone (1 μm), guanethidine (10 μm), a mixture of propranolol (3 μm) and phentolamine (3 μm), tetrodotoxin (1 μm), indomethacin (10 μm), atropine (1 μm), a mixture of methysergide (2.5 μm) and ketanserin (2.5 μm), a mixture of mepyramine (10 μm) and cimetidine (10 μm), and saralasin (10 μm) or when strips were desensitized to substance P and neurotensin.
These results suggest the localization of specific Gal receptors on the surface of smooth muscle cells of rat fundus.
The galanin analogues [d‐Trp2]‐rGal, [NLe4]‐rGal, [d‐Ala7]‐rGal, [d‐Trp2‐NLe4‐d‐Ala7]‐rGal and fragments [Cys23]‐Gal (1–23), Gal (1–18) were fully active. In contrast, rGal (3–29) was completely inactive and showed no antagonistic properties to the contractile effect of intact galanin.
The order of potency of the galanin peptides, analogues and fragments to contract rat fundus strips was: pGal > rGal > [NLe4]‐rGal > [Cys23]‐Gal (1–23) > Gal (1–18) > [d‐Ala7]‐rGal > [Trp2]‐rGal > [d‐Trp2‐NLe4‐d‐Ala7]‐rGal.
The data originating from our structure‐activity study suggest that the C‐terminal portion of Gal contributes mainly to the affinity of Gal receptors whereas the N‐terminal portion of Gal is responsible for the full activation of Gal receptors in this tissue. In particular the amino acids in position 1 and 2 of Gal (Gly‐Trp) appear to be essential for binding and intrinsic activity.
Reserpine induces vascular α2‐adrenergic supersensitivity and platelet α2‐adrenoceptor up‐regulation in dog
Authors: Estan Luis , Senard Jean‐Michel , Tran Marie‐Antoinette , Montastruc Jean‐Louis , Berlan Michel 
Published: July 2012

The aim of the present study was to investigate the influence of catecholamine levels on the regulation of α2‐adrenoceptor sensitivity in dogs.
Blood pressure and heart rate values at rest, plasma catecholamine levels, platelet and adipocyte α2‐adrenoceptors as well as the α2‐mediated cardiovascular responses to clonidine (10 μg kg−1 i.v., after α1‐, β‐adrenoceptor plus muscarinic blockade) or noradrenaline (0.5, 1, 2 and 4 μg kg−1 i.v. after α1‐ and β‐adrenoceptor blockade) were measured before and after reserpine treatment (0.1 mg kg−1 day−1 s.c. over 15 days).
Reserpine induced a significant decrease in resting systolic and diastolic blood pressures (213 ± 2/87 ± 6 mmHg before vs 158 ± 5/59 ± 3mmHg after treatment) as well as in heart rate (91 ± 2 beats min−1 before vs 76 ± 3 beats min−1 after treatment).
A 5 min tilt test performed under chloralose anesthesia, failed to modify blood pressure before treatment whereas it induced a significant fall in the same animals after the 15 day treatment. Plasma levels of noradrenaline significantly decreased (262 ± 58 vs 66 ± 31 pg ml−1) whereas plasma adrenaline levels were unchanged.
The α2‐mediated pressor responses to noradrenaline were significantly increased after reserpine. Clonidine induced a marked pressor effect (+72 and +45% in systolic and diastolic blood pressures respectively) after reserpine treatment. This effect was suppressed by administration of RX‐821002, a new specific α2‐adrenoceptor antagonist.
Reserpine treatment significantly increased platelet α2‐adrenoceptor number (identified with [3H]‐yohimbine or [3H]‐RX821002) with no change in Kd values. α2‐Adrenoceptor number remained unchanged in adipocytes (identified with [3H]‐RX821002).
These results show that a 15 day treatment with reserpine induces a vascular α2‐adrenergic supersensitivity and an up‐regulation in platelet α2‐adrenoceptors. In contrast, this phenomenon does not involve all the tissues since adipocyte α2‐adrenoceptors escape the effect of reserpine. We suggest that the levels of plasma noradrenaline play an important role in the regulation of the platelet and vascular α2‐adrenoceptors. In contrast, adipocyte α2‐adrenoceptors are not affected by changes in plasma noradrenaline levels.
Factors influencing the onset of ouabain inhibition of Na,K‐ATPase from guinea‐pig myocardium
Authors: Ebner F. 
Published: July 2012

The onset of ouabain inhibition was quantified by analysis with an integrated rate equation from experiments in which the activity of Na,K‐ATPase from guinea‐pig myocardium had been altered with adenosine 5′‐triphosphate (ATP, 0.3–9 mmoll−1) in the absence and presence of a detergent.
Under control conditions with increasing ouabain (0.1–100 μmoll−1) and ATP (0.3–1 mmoll−1) concentrations, inhibition developed faster. The acceleration by ouabain became less effective at saturating concentrations leading to a non‐linear relationship between pseudo‐first‐order rate constants of inhibition and ouabain concentration. With a rise of ATP to 3 and 9 mmoll−1, i.e., near total Mg concentration (5 mmoll−1), inhibition was retarded presumably because the free concentrations of Mg and uncomplexed ATP changed. Varying the ATP concentration had little effect on ouabain potency at steady state; Hill coefficients were < 1.
The detergent alamethicin (23 μg ml−1) neither interfered with Na,K‐ATPase activity nor with inhibition at steady state but accelerated its onset. This supports a role for a lipid barrier in the development of inhibition.
While the reaction of low concentrations of ouabain with the receptors seemed to govern inhibition rate, with an increase in steroid concentration in the presence of alamethicin, ATP‐dependent enzyme activity interfered with the onset of inhibition. The transition of the enzyme between ouabain‐sensitive and ATP‐hydrolytic conformations consequently causes the non‐linear concentration‐dependence of pseudo‐first‐order rate constants. As the Hill coefficient was < 1, a reaction of ouabain with two receptors also could have contributed to the special concentration‐dependence of inhibition rates.