bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contribution of ATP and nitric oxide to NANC inhibitory transmission in rat pyloric sphincter
Authors: Soediono Prajitno , Burnstock Geoffrey 
Published: July 2012

Changes in isometric tension were recorded from circular muscle strips of rat pyloric sphincter in vitro, in response to electrical field stimulation and exogenously applied muscle relaxants.
Concentration‐response relationships were studied for relaxations to exogenously applied adenosine 5′‐triphosphate (ATP) and two analogues, 2‐methylthioATP (2‐MeSATP) and α,β‐methylene ATP (α,β‐MeATP). These drugs evoked concentration‐dependent relaxation of rat pyloric sphincter with an order of potency 2‐MeSATP > ATP > > α,β‐MeATP, indicating the presence of P2Y‐purinoceptors. The IC50 value of each nucleotide was: 2‐MeSATP, 5.0 × 10−8 m; ATP, 7.9 × 10−6 m; α,β‐MeATP showed only slight activity at a concentration of 0.1 mm.
Frequency‐response relationships for relaxations evoked by electrical field stimulation (EFS) were studied in the absence and presence of 10 μm NG‐nitro‐L‐arginine methyl ester (L‐NAME, an inhibitor of nitric oxide (NO) synthesis) and 20 μm reactive blue 2 (a P2y‐purinoceptor antagonist). It was found that these substances significantly reduced the relaxant response of rat pyloric sphincter to EFS by 40% and 50% respectively. In the presence of both L‐NAME and reactive blue 2 the responses were reduced by 75%.
Concentration‐response relationships were studied for ATP and 2‐MeSATP in the presence of L‐NAME. It was found that L‐NAME did not significantly inhibit the relaxant responses to these drugs.
Concentration‐response relationships for ATP and noradrenaline were studied in the presence of reactive blue 2 (20 μm); the P2Y‐antagonist significantly inhibited the relaxant response to ATP, but not that to noradrenaline.
The distribution of nitric oxide synthase in rat pyloric sphincter was investigated immunohis‐tochemically, with immunoreactive nerve fibres found throughout the circular muscle layer and myenteric plexus of the sphincter.
While abundant vasoactive intestinal polypeptide (VIP)‐containing nerve fibres were demonstrated immunohistochemically in the pyloric sphincter, relaxations to VIP (1 nm‐0.3 μm) were not observed in this preparation.
It is concluded that ATP, acting through P2Y‐purinoceptors, and NO contribute to NANC inhibitory neurotransmission in rat pyloric sphincter. NO appeared to contribute to the later component of NANC relaxation. The action of ATP was not mediated by NO, and VIP did not contribute to the NANC inhibitory responses in this preparation.
Atypical β‐adrenoceptors in the rat isolated common carotid artery
Authors: Oriowo Mabayoje Ayotunde 
Published: July 2012

The possible existence of atypical β‐adrenoceptors in vascular smooth muscle of the rat common carotid artery was examined in this study.
Isoprenaline produced concentration‐dependent relaxation of noradrenaline (10−7 m) precontracted ring segments of the carotid artery. The relaxation was not affected by endothelial denudation.
Propranolol (10−8 m‐3 × 10−7 m) shifted the isoprenaline curve to the right without suppressing the maximum response. However, the slope (0.74) of the Schild plot was significantly (P < 0.05) less than 1.
Salbutamol (fe), CGP 12177 and BRL 37344 (ft) also concentration‐dependently relaxed noradrenaline precontracted artery segments. These relaxations were not affected by propranolol (10−7 m). Pretreatment of the artery segments with BRL 37344 did not desensitize the tissue to the relaxant effect of isoprenaline, CGP 12177 and salbutamol.
It is concluded that atypical β‐adrenoceptors exist in vascular smooth muscle of the common carotid artery.
Electrophysiological subtypes of inhibitory P1 purinoceptors on myenteric neurones of guinea‐pig small bowel
Authors: Christofi F.L. , Wood J.D. 
Published: July 2012

Conventional intracellular microelectrode techniques were used to subclassify P1 purinoceptors linked to reduction of cell input resistance, steady‐state hyperpolarization of the membrane potential, or inhibition of fast e.p.s.ps, in neurones of microdissected myenteric plexus preparations from guinea‐pig ileum. The potencies of P1 purinoceptor agonists were estimated in neurones that were current clamped to a fixed membrane potential.
In AH/Type 2 neurones, the A2 agonist, CGS 21680, the A1 agonist, CCPA or the mixed A1‐A2 agonist, NECA, suppressed excitability by reducing input resistance (40–50% max.) and causing hyperpolarization (20–25 mV max.). CGS 21680 (0.1‐1 μm) enhanced the after‐hyperpolarizing potential.
From cumulative dose‐response data, the potency order for reducing input resistance was CCPA (IC50 = 5.1 ± 2.2nM) > > > CGS 21680 (IC50 = 5.6 ± 2.5 μm). This effect was reversed by the A1 antagonist, CPT (EC50 = 65 ± 11 nm).
In contrast, the potency order for membrane hyperpolarization was CCPA (IC50 = 61 ± 23 nm) = CGS 21680 (IC50 = 290 ± 90 nm) ≥ NECA (IC50 = 450 ± 100 nm). Hyperpolarization elicited by CCPA was sensitive to the A1‐A2 antagonist, DPSPX.
Agonists suppressed fast e.p.s.ps, but not DMPP responses, with an order of CCPA (IC50 = 8.1 ± 3.0 nm) > > > CGS 21680 (IC30 = 10 ± 2.9 μm).
In conclusion, the excitability of AH/Type 2 neurones is suppressed by activation of high affinity A1 receptors that may be linked to a cyclic AMP‐dependent pathway, leading to increase in calcium‐dependent potassium conductance and enhancement of the after‐hyperpolarizing potential. Activation of lower affinity non A1 receptors linked to a cyclic AMP‐independent pathway reduces excitability and leads mainly to a steady‐state hyperpolarization. Adenosine also suppresses nicotinic cholinergic transmission by activating presynaptic high affinity A1 receptors.
Enhancement of retinal acetylcholine release by DAMGO: possibly a direct opioid receptor‐mediated excitatory effect
Authors: Neal M.J. , Paterson S.J. , Cunningham J.R. 
Published: July 2012

An eye‐cup preparation in anaesthetized rabbits was used to examine opioid modulation of acetylcholine (ACh) release from cholinergic neurones in the retina.
The μ‐opioid receptor agonist, [D‐Ala2, MePhe4, Gly‐ol5]‐enkephalin (DAMGO), when applied locally to the retina at concentrations between 1–30 μm significantly increased the light‐evoked release of ACh. The effect of DAMGO was completely blocked by the selective μ‐receptor antagonist CTOP but the k‐receptor antagonist nor‐binaltorphimine (norBNI) did not affect the action of DAMGO on ACh release indicating that the opioid produced its effect by activation of μ‐receptors (the rabbit retina has negligible δ‐receptors).
Blockade with bicuculline and strychnine of GABAergic and glycinergic inputs to the cholinergic neurones did not affect the action of DAMGO on ACh release. Also DAMGO did not reduce the potassium‐evoked release of either GABA or glycine from rat isolated retinas.
Exposure of the rabbit retina to a combination of an A1‐adenosine receptor antagonist, 8‐cyclopentyl‐1,3 dipropylxanthine (DPCPX), and adenosine deaminase did not affect the enhancing action of DAMGO on the light‐evoked release of ACh.
When the retina in the rabbit eye‐cup was exposed to kainate, the release of ACh was increased by approximately three times the resting release. In the presence of DAMGO the kainate‐evoked release of ACh was enhanced by 44%.
These experiments show that activation of μ‐opioid receptors by DAMGO increases the release of ACh elicited by physiological stimulation (flickering light). Since we could find no evidence that DAMGO reduces inhibitory inputs to the cholinergic neurones, it seems that the enhancing action of DAMGO on the light‐evoked release of ACh involves a direct excitatory effect rather than disinhibition. This conclusion is supported by the enhancing action of DAMGO on the kainate‐evoked release of ACh because kainate is thought to act directly on the cholinergic neurones.
Role of endogenous endothelin in myocardial and coronary endothelial injury after ischaemia and reperfusion in rats: studies with bosentan, a mixed ETA‐ETB antagonist
Authors: Richard Vincent , Kaeffer Nathalie , Hogie Manuela , Tron Christophe , Blanc Thierry , Thuillez Christian 
Published: July 2012

Previous studies suggested that endothelin‐1 (ET‐1) may play a role in myocardial ischaemia and reperfusion. This study was designed to test the effect of a new nonpeptide antagonist of endothelin ETA and ETB receptors, bosentan, on myocardial infarct size, ventricular arrhythmias, and coronary endothelial dysfunction after ischaemia and reperfusion.
Anaesthetized male Wistar rats were subjected to 20min ischaemia (left coronary artery occlusion) followed by 1 h (for the evaluation of coronary endothelial dysfunction) or 2 h (for the evaluation of infarct size) reperfusion, or 5 min ischaemia followed by 15 min reperfusion (for the evaluation of reperfusion arrhythmias). Vascular studies were performed on 1.5‐2 mm coronary segments (internal diameter 250–300 μm) removed distal to the site of occlusion and mounted in wire myographs for isometric tension recording. Area at risk and infarct size were determined by Indian ink injection and triphenyl tetrazolium staining, using computerized analysis of enlarged sections after colour video acquisition.
Bosentan, administered at a dose which virtually abolished the pressor response to big ET‐1 (3 mg kg−1, i.v. before ischaemia) did not affect heart rate, arterial pressure or the rate pressure product before ischaemia, during ischaemia and during reperfusion. Bosentan did not affect the incidence of reperfusion‐induced ventricular fibrillation (controls: 86%, n = 14; bosentan: 93%, n = 15), and did not modify infarct size (% of area at risk: controls: 63 ± 4, n = 10; bosentan: 60 ± 6, n = 8). Ischaemia followed by reperfusion markedly reduced the endothelium‐dependent relaxations to acetylcholine (maximal response: sham: 59 ± 4%, n = 9; ischaemia‐reperfusion: 26 ± 6%, n = 8; P < 0.01), characteristic of reperfusion‐induced endothelial dysfunction, and this dysfunction was not prevented by bosentan (maximal response to acetylcholine: 25 ± 5%, n = 9; P < 0.01 vs sham; P = NS vs ischaemia/reperfusion).
These experiments suggest that endogenous endothelin does not contribute to myocyte or coronary endothelial injury in this rat model of ischaemia and reperfusion.
Regional and species differences in glyburide‐sensitive K+ channels in airway smooth muscles as estimated from actions of KC 128 and levcromakalim
Authors: Kamei Kenshi , Yoshida Shohshin , Imagawa Jun‐Ichi , Nabata Hiroyuki , Kuriyama Hirosi 
Published: July 2012

The purpose of the present experiments was to elucidate the differences in actions of two K+ channel openers, KC 128 and levcromakalim, on the carbachol‐induced contraction, membrane potential and 86Rb+ efflux of the dog tracheal and bronchial smooth muscles. Furthermore, we compared the effects of these agents on guinea‐pig and human airway smooth muscles.
In the dog tracheal and bronchial smooth muscle tissues, levcromakalim induced a concentration‐dependent relaxation of the carbachol‐induced contraction. The IC50 values were 0.35 μm (pIC50: 6.46 ± 0.10, n = 9) and 0.55 μm (pIC50: 6.26 ± 0.07, n = 5), respectively. KC 128 relaxed bronchial smooth muscles precontracted by carbachol with an IC50 value of 0.19 μm (pICso: 6.73 ± 0.10, n = 7). However, KC 128 had almost no effect on the contraction evoked by carbachol in the trachea (IC50 > 10 μm). The relaxations induced by levcromakalim and KC 128 were antagonized by glyburide (0.03‐1 μm) but not by charybdotoxin (100 nm).
Levcromakalim (1 μm) hyperpolarized the membrane of both dog tracheal and bronchial smooth muscle cells, whereas KC 128 (1 μm) hyperpolarized the membrane of bronchial but not of tracheal smooth muscle cells.
Levcromakalim (10 μm) increased 86Rb+ efflux rate from both tracheal and bronchial smooth muscle tissues but KC 128 (10 μm) increased 86Rb+ efflux rate only from bronchial and not tracheal smooth muscle tissues. Glyburide (1 μm) prevented the hyperpolarization and the 86Rb+ efflux induced by these agents at the same concentration as observed for mechanical responses.
Both KC 128 and levcromakalim relaxed the guinea‐pig isolated tracheal smooth muscles precontracted by carbachol (100 nm), histamine (3μm) or U46619 (10 nm). KC 128 was approximately 10 times more potent than levcromakalim for each agonist.
In human bronchial smooth muscles, levcromakalim but not KC 128 induced a concentration‐dependent relaxation of the carbachol‐induced contraction.
It is concluded that KC 128 has relaxant and hyperpolarizing effects in the dog bronchial and guinea‐pig tracheal smooth muscles, but not in the dog tracheal and human bronchial smooth muscles. On the other hand, levcromakalim acts consistently on all the above airway smooth muscle tissues. These results indicate that there are regional and species differences in distribution of K+ channels, and at least two different K+ channel opener‐ and glyburide‐sensitive K+ channels are present in the dog airway smooth muscles.
Inhibition by gomisin C (a lignan from Schizandra chinensis) of the respiratory burst of rat neutrophils
Authors: Wang Jih P. , Raung Shue L. , Hsu Mei F. , Chen Chien C. 
Published: July 2012

The possible mechanisms of action of the inhibitory effect of gomisin C on the respiratory burst of rat neutrophils in vitro was investigated.
The peptide formyl‐Met‐Leu‐Phe (FMLP) induced superoxide anion (O2−) formation and O2 consumption, which was inhibited by gomisin C in a concentration‐dependent manner (IC50 21.5 ± 4.2 μg ml−1 for O2− formation). Gomisin C also suppressed O2− formation and O2 consumption at low concentrations of phorbol myristate acetate (PMA) with an IC50 value of 26.9 ± 2.1 μg ml−1 for O2− formation. However, gomisin C did not affect the responses induced by a high concentration of PMA.
Gomisin C had no effect on O2− generation and uric acid formation in the xanthine‐xanthine oxidase system, and failed to alter O2− generation during dihydroxyfumaric acid (DHF) autoxidation, indicating that it does not scavenge superoxide.
Like trifluoperazine (TFP), gomisin C attenuated the activity of PMA‐activated neutrophil particulate NADPH oxidase in a concentration‐dependent manner.
Gomisin C reduced the elevations of cytosolic free Ca2+ in neutrophils stimulated by FMLP in the presence or absence of EDTA. Cyclopiazonic acid (CPA) induced the release of Ca2+ from intracellular stores and this was also reduced by gomisin C. However, the Ca2+ influx pathway activated by CPA was not affected by gomisin C.
The cellular cyclic AMP level was markedly increased by forskolin, but not by gomisin C. Moreover, the inositol phosphate levels in FMLP‐activated neutrophils were not affected by gomisin C.
These results show that the inhibitory action of gomisin C on the respiratory burst is not mediated by changes in cellular cyclic AMP or in inositol phosphates, or by scavenging O2− released from neutrophils, but may be mediated partly by the suppression of NADPH oxidase and partly by the decrease of cytosolic Ca2+ released from an agonist‐sensitive intracellular store.
Role of 5‐HT3 receptors in basal and K+‐evoked dopamine release from rat olfactory tubercle and striatal slices
Authors: Zazpe A. , Artaiz I. , Del Río J. 
Published: July 2012

The present study was aimed at examining the role of 5‐HT3 receptors in basal and depolarization‐evoked dopamine release from rat olfactory tubercle and striatal slices. [3H]‐dopamine ([3H]‐DA) release was measured in both brain regions and endogenous dopamine release from striatal slices was also studied.
The selective 5‐HT3 receptor agonist 2‐methyl‐5‐HT (0.5–10μm) produced a concentration‐dependent increase in [3H]‐DA efflux evoked by K+ (20 μm) from slices of rat olfactory tubercle. 1‐Phenylbiguanide (PBG) and 5‐HT also increased K+‐evoked [3H]‐DA efflux.
5‐HT (1–100 μm) increased in a concentration‐dependent manner basal [3H]‐DA release from olfactory tubercle and striatal slices as well as endogenous DA release from striatal slices. The selective 5‐HT3 receptor agonists 2‐methyl‐5‐HT and 1‐phenylbiguanide were weaker releasing agents. In all cases, the release was Ca2+ independent and tetrodotoxin insensitive.
5‐HT3 receptor antagonists such as ondansetron, granisetron and tropisetron (0.2 μm) significantly blocked the enhanced K+‐evoked [3H]‐DA efflux from rat olfactory tubercle slices induced by 2‐methyl‐5‐HT. A ten fold higher concentration of the 5‐HT2 receptor antagonist ketanserin was ineffective.
Much higher concentrations, up to 50 μm, of the same 5‐HT3 receptor antagonists did not block the increase in basal [3H]‐DA release from striatal or olfactory tubercle slices induced by 5‐HT or the release of endogenous DA induced by 5‐HT from striatal slices.
The DA uptake blocker nomifensine (10 μm) did not modify the enhancement in K+‐evoked [3H]‐DA efflux from rat olfactory tubercle slices induced by 2‐methyl‐5‐HT. However, both nomifensine and cocaine significantly blocked the increase in basal dopamine release, either tritiated or endogenous, induced by 5‐HT.
These results indicate that 5‐HT3 receptors only modulate DA release when the terminal fields of dopaminergic systems have been activated. In basal conditions, 5‐HT3 receptor agonists enhance DA release through a carrier‐mediated mechanism. This may be of therapeutic relevance for the possible use of 5‐HT3 receptor antagonists under conditions of abnormal activation of the dopaminergic system.
The transhepatic action of ATP on the hepatic arterial and portal venous vascular beds of the rabbit: the role of nitric oxide
Authors: Browse Dominic J. , Mathie Robert T. , Benjamin Irving S. , Alexander Barry 
Published: July 2012

The effect of bolus administration of adenosine 5′‐triphosphate (ATP) into the portal vein on hepatic arterial pressure (the transhepatic action of ATP) and portal venous pressure, and the contribution of nitric oxide towards these responses, was studied in the in vitro dual‐perfused rabbit liver.
At basal tone, hepatic arterial and portal venous vasoconstriction followed ATP injection, while at a tone raised with methoxamine (10−6‐10−5m) ATP caused hepatic arterial vasodilatation, and a phasic vasodilatation followed by vasoconstriction in the portal venous vascular bed.
To determine whether the transhepatic arterial dilatation was due to the diffusion of nitric oxide (NO) from the portal venous vasculature, NG‐nitro‐L‐arginine methyl ester (L‐NAME, 100 μm), an inhibitor of NO synthesis, was infused selectively into the portal vein. L‐NAME infusion potentiated portal venous vasoconstriction to ATP (‐log M ED50 5.32 ± 0.31 to 6.51 ± 0.43, P < 0.05, Student's paired / test) indicating the possible inhibition of a NO‐mediated vasodilator component of the portal venous response to ATP. There was, however, no demonstrable difference in the transhepatic arterial vasodilatation induced by ATP during this infusion.
Simultaneous perfusion of both the hepatic arterial and portal venous inflows with L‐NAME (100 μm) resulted in a significant decrease in the amplitude of hepatic arterial responses to ATP demonstrating that these responses were ultimately mediated by an NO‐dependent mechanism.
This study has thus demonstrated a vasodilator component of the portal venous response to ATP that is NO‐mediated. It also provides evidence that it is not portally‐derived NO, but NO released from the hepatic arterial vascular bed, that accounts for the hepatic arterial vasodilatation to intra‐portal administration of ATP. This implies that ATP itself, and not a second messenger, diffuses from the portal venous to hepatic arterial vascular bed to elicit the hepatic arterial response.
Pharmacological actions of the selective and non‐selective β‐adrenoceptor antagonists celiprolol, bisoprolol and propranolol on human bronchi
Authors: Hauck R.W. , Schulz Ch. , Emslander H.P. , Böhm M. 
Published: July 2012

The pharmacological actions of the β‐adrenoceptor antagonists, celiprolol, bisoprolol and propranolol were investigated in human lung tissue by radioligand binding experiments as well as in human isolated bronchi by functional experiments in organ baths.
Data from lung tissue were compared to those obtained from myocardial membranes.
Lung tissue was obtained from 10 patients having undergone lung resection for bronchial carcinoma and myocardial tissue from a patient who had received a heart transplantation.
In radioligand binding experiments, celiprolol exhibited a high affinity binding to β1,‐adrenoceptors in heart and a low affinity binding to β2‐adrenoceptors in lung tissue. The selectivity obtained for the β1‐adrenoceptor was calculated to a factor of eleven.
Compared to bisoprolol and propranolol, celiprolol elicited the lowest affinity for the β‐adrenoceptor, as judged from the K1‐values.
In the absence and presence of the guanine nucleotide Gpp(NH)p celiprolol did not affect receptor binding.
In functional experiments on intact bronchi, celiprolol, bisoprolol and propranolol failed to produce relaxation (± forskolin) or a significant difference in efficacy in antagonizing the relaxant effects of isoprenaline. However, a rank order of potencies was revealed (propranolol: bisoprolol.celiprolol = 46: 12:1).
Plasma concentrations for celiprolol and bisoprolol usually achieved in vivo were below the IC50 value obtained in vitro. In contrast, for propranolol, plasma concentrations were nearly identical with the IC50 value.
It is concluded that celiprolol is a selective β1‐adrenoceptor antagonist on human heart and has no agonistic properties on intact human bronchi. Compounds such as celiprolol and bisoprolol may in comparison to propranolol, possess reasonable therapeutic advantages in the treatment of patients with obstructive lung disease due to their low affinity for β2‐adrenoceptors.