bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition by endothelin‐1 of cholinergic nerve‐mediated acetylcholine release and contraction in sheep isolated trachea
Authors: Henry Peter J. , Shen Albert , Mitchelson Fred , Goldie Roy G. 
Published: July 2012

The relative roles of ETA and ETB receptor activation on cholinergic nerve‐mediated contraction and acetylcholine (ACh) release were examined in sheep isolated tracheal smooth muscle.
Electrical field stimulation (EFS; 90 V, 0.5 ms duration, 1 Hz, 10 s train) applied to sheep isolated tracheal smooth muscle strips induced monophasic contractile responses that were abolished by either 1 μm tetrodotoxin or 0.1 μm atropine, but were insensitive to 10 μm hexamethonium and 100 μm L‐NAME. Thus, EFS‐induced contractions resulted from the spasmogenic actions of ACh released from parasympathetic, postganglionic nerves.
As expected, sheep isolated tracheal smooth muscle preparations did not contract in response to the ETB receptor‐selective agonist, sarafotoxin S6c (0.1–100 nM). However, sarafotoxin S6c caused a concentration‐dependent and transient inhibition of EFS‐induced contractions. The inhibitory effect induced by a maximally effective concentration of sarafotoxin S6c (10 nM; 72.1 ± 5.7%, n = 6) was abolished in the presence of the ETB receptor‐selective antagonist BQ‐788 (1 μm). Contractile responses to exogenously administered ACh (10 nM‐0.3 mM) were not inhibited by sarafotoxin S6c (1 or 10 nM; n = 7).
In contrast to sarafotoxin S6c, endothelin‐1 induced marked contractions in sheep isolated tracheal smooth muscle. These contractions were inhibited by BQ‐123, consistent with an ETA receptor‐mediated response. In the presence of BQ‐123 (3 μm), endothelin‐1 produced a concentration‐dependent inhibition of EFS‐induced contractions (30 nM endothelin‐1, 68.9 ± 10.2% inhibition, n = 5). These responses were inhibited by 1 μm BQ‐788, indicative of an ETB receptor‐mediated process. Endothelin‐1 was about 3 fold less potent than sarafotoxin S6c.
EFS (90 V, 0.5 ms duration, 1 Hz, 15 min train) induced the release of endogenous ACh (1.94 ± 0.28 pmol mg−1 tissue, n = 12), as assayed by h.p.l.c. with electrochemical detection. EFS‐induced release of ACh was inhibited to a similar extent by 100 nM endothelin‐1 (47 ± 4%, n = 9) and 10 nM sarafotoxin S6c (46 ± 9%, n = 3). These effects of endothelin‐1 on ACh release were inhibited by 1 μm BQ‐788 alone (n = 4), by BQ‐788 in the presence of 3 μm BQ‐123 (n = 4), but not by 3 μm BQ‐123 alone (n = 5).
In summary, sheep isolated tracheal smooth muscle contains two anatomically and functionally distinct endothelin receptor populations. ETA receptors located on airway smooth muscle mediate contraction, whereas ETB receptors appear to exist on cholinergic nerves that innervate tracheal smooth muscle cells and mediate inhibition of ACh release. The inhibitory effect of ETB receptor stimulation on cholinergic neurotransmission is in stark contrast to the enhancing effects hitherto described in the airways.
Adenosine inhibitory effect on enhanced growth of aortic smooth muscle cells from streptozotocin‐induced diabetic rats
Authors: Parés‐Herbuté N. , Hillaire‐Buys D. , Etienne P. , Gross R. , Loubatières‐Mariani M.‐M. , Monnier L. 
Published: July 2012

There is evidence to suggest that adenosine may regulate arterial smooth muscle cell (SMC) growth and proliferation, which is a key event in atherogenesis. This regulation may be mediated via adenylate cyclase. As diabetes is a known risk factor for atherosclerosis, we investigated the growth of aortic SMC from diabetic rats in primary culture and their sensitivity to adenosine and to adenylate cyclase activity.
Diabetes was induced with streptozotocin (STZ, 66 mg kg−1, i.p.) Aortic SMC primary cultures were prepared from STZ‐diabetic and age‐matched rats 5 weeks after the STZ injection.
SMC from STZ‐diabetic rats grew faster and reached greater densities at confluence than those from non‐diabetic animals.
Adenosine inhibited growth in both control and diabetic SMC. However, cells from STZ‐diabetic rats were apparently more sensitive to adenosine.
Direct activation of adenylate cyclase by forskolin induced a dose‐dependent growth inhibition, similar in both groups of cells.
Cholera toxin, an activator of stimulatory GTP‐binding protein (Gs), induced a similar growth inhibitory response in non‐diabetic and diabetic SMC. Pertussis toxin (PTX), an inactivator of inhibitory GTP‐binding protein (Gi), did not itself affect SMC growth. However, PTX increased dose‐dependently the growth inhibition induced by adenosine in SMC from non‐diabetic rats but not in SMC from diabetic rats.
These findings suggest a functional abnormality in Gi activity in SMC from diabetic rats, that would explain the increased sensitivity to the nucleoside. This impaired inhibitory pathway may reflect changes in the growth regulation of SMC in experimental diabetic states.
Mechanism of inhibition of calcium channels in rat nucleus tractus solitarius by neurotransmitters
Authors: Rhim Hyewhon , Toth Peter T. , Miller Richard J. 
Published: July 2012

High‐threshold Ca2+ channel currents were measured every 15 s following a 200 ms voltage step from −80 mV to 0 mV in order to study the coupling mechanism between neurotransmitter receptors and Ca2+ channels in neurones acutely isolated from the nucleus tractus solitarius (NTS) of the rat.
Application of 30 μm baclofen (GABAB receptor agonist) caused 38.9 ± 1.2% inhibition of the peak inward Ba2+ current (IBa2+) in most NTS cells tested (n = 85 of 88). Somatostatin, 300 nM, also reduced IBa2+ by 31.3 ± 1.6% in 53 cells of 82 tested.
Activation of μ‐opioid‐, GABAB‐ or somatostatin‐receptors inhibited both N‐ and P/Q‐type Ca2+ channels.
The inhibition of Ca2+ currents by DAMGO (μ‐opioid receptor agonist), baclofen and somatostatin was reduced by treatment with pertussis toxin and partially relieved by application of a 50 ms conditioning prepulse to +80 mV. This suggests that a pertussis toxin‐sensitive G‐protein was involved in the neurotransmitter‐mediated action in the observed inhibition of Ca2+ currents.
Intracellular loading with an antiserum raised against the amino terminus of Goα (GC/2) markedly attenuated the somatostatin‐induced inhibition, but did not block the DAMGO‐ and baclofen‐induced inhibition.
These findings suggest at least two different pertussis toxin‐sensitive G‐protein‐mediated pathways are involved in receptor‐induced inhibition of Ca2+ currents in the NTS.
The induction of a biphasic bronchospasm by the ETB agonist, IRL 1620, due to thromboxane A2 generation and endothelin‐1 release in guinea‐pigs
Authors: Noguchi Seiji , Kashihara Yasunari , Bertrand Claude 
Published: July 2012

IRL 1620 (0.01‐0.1 mg kg−1, i.v.), a selective endothelin B (ETB) receptor agonist, induced a dose‐dependent biphasic increase in total lung resistance and a decrease in dynamic compliance in anaesthetized and artificially ventilated guinea‐pigs. After intravenous injection of IRL 1620 (0.03 mg kg−1), the first phase was observed within 2 min whereas the second phase started between 5 and 10 min after injection and was long lasting.
In order to characterize which endothelin receptors are involved in both phases of bronchoconstriction, we studied the effect of ETA and ETB receptor antagonists (BQ 123 and BQ 788, respectively). BQ 788 (0.1‐1 mg kg−1, i.v.) inhibited, in a dose‐dependent manner, both phases of bronchoconstriction. BQ 123 (3 mg kg−1, i.v.) markedly inhibited (by 76%) the second phase of bronchoconstriction but had no effect on the early component of the response.
The effect of atropine, neurokinin‐1 (NK1) and neurokinin‐2 (NK2) receptor antagonists (SR140333 and SR48968, respectively) were tested to investigate the possible involvement of cholinergic and sensory nerve activation, respectively, in the response to IRL 1620. Likewise, the role of arachidonic acid metabolites (leukotriene D4 antagonist, ONO‐1078 and thromboxane A2 (TXA2) inhibitor, OKY‐046) in this response was also investigated. OKY‐046 (1 mg kg−1, i.v.) and atropine (1 mg kg−1, i.v.) partially inhibited the first phase (by 80% and 20%, respectively) without affecting the late phase of bronchoconstriction. Neither ONO‐1078 (1 mg kg−1, i.v.) nor the combination of SR140333 (0.2 mg kg−1, i.v.) and SR 48968 (0.2 mg kg−1, i.v.) modified IRL 1620‐induced bronchoconstriction.
A low dose of IRL 1620 (0.005 mg kg−1, i.v.) induced a monophasic bronchoconstriction. Pretreatment by phosphoramidon (100 μmol kg−1, i.v.) restored the second phase of bronchoconstriction. In this condition, BQ 123 (3 mg kg−1, i.v.) was able to inhibit partially the second phase of bronchoconstriction.
These results suggest that both phases of bronchoconstriction induced by IRL 1620 were mediated primarily by ETB receptor activation, the first phase being a consequence of TXA2 and acetylcholine release. The inhibition by an ETA receptor antagonist and the restoration by a neutral endopeptidase (NEP) inhibitor of the second phase of bronchoconstriction suggests that primary activation of ETB receptors leads to autocrine/paracrine endothelin‐1 (ET‐1) release that would subsequently cause profound bronchoconstriction through both ETA and ETB receptor activation.
Central B2 receptor involvement in the antinociceptive effect of bradykinin in rats
Authors: Pelá I.R. , Rosa A.L. , Silva C.A.A. , Huidobro‐Toro J.P. 
Published: July 2012

The effect of intracerebroventricular (i.c.v.) injection of bradykinin (BK) and related peptides was tested on the dental pulp electrical stimulation threshold (DPEST) in rats.
BK (4, 8 and 16 nmol) induced a dose‐dependent increase of DPEST, indicative of an antinociceptive effect.
I.c.v. injection of equimolar doses of BK‐related peptides, Lys‐BK and Met‐Lys‐BK, also induced an increase of DPEST, but the magnitude of the effect was not as intensive as that induced by BK, when the maximum increase of DPEST was considered. The peptide T‐kinin induced a short lasting and weak antinociceptive effect.
The B1 agonist, des‐Arg9‐BK (8 nmol) induced a significant antinociceptive effect, but this was not as intensive as that induced by BK.
The B2 antagonist D‐Arg0‐Hyp3‐Thi5, 8‐D‐Phe7‐BK (D‐Arg0) competitively antagonized the BK‐induced antinociception. Likewise, Hyp3‐Thi5, 8‐D‐Phe7‐BK (Hyp) also antagonized BK effect. However, the compound Thi5, 8‐D‐Phe7‐BK (Thi), initially considered a pure BK antagonist, induced an antinociceptive effect, supporting previous observations that this peptide can also act as a partial agonist.
It is concluded that the dose‐dependent antinociceptive effect induced by i.c.v. injection of BK is mediated by the stimulation of brain B2 receptors.
VIP‐ and PACAP‐mediated nonadrenergic, noncholinergic inhibition in longitudinal muscle of rat distal colon: involvement of activation of charybdotoxin‐ and apamin‐sensitive K+ channels
Authors: Kishi Masami , Takeuchi Tadayoshi , Suthamnatpong Naowarat , Ishii Toshiaki , Nishio Hideaki , Hata Fumiaki , Takewaki Tadashi 
Published: July 2012

The mediators of nonadrenergic, noncholinergic (NANC) inhibitory responses in longitudinal muscle of rat distal colon were studied.
An antagonist of pituitary adenylate cyclase activating peptide (PACAP) receptors, PACAP6–38, concentration‐dependently inhibited the rapid relaxation of the longitudinal muscle induced by electrical field stimulation (EFS), resulting in a maximal inhibition of 47% at 3 μm.
PACAP6–38 inhibited the relaxation by 75% in the presence of the vasoactive intestinal peptide (VIP) receptor antagonist, VIP10–28 at μm, which inhibited the relaxation by 44%.
An antagonist of large conductance Ca2+‐activated K+ channels, charybdotoxin, concentration‐dependently inhibited the rapid relaxation of the longitudinal muscle, resulting in a maximal inhibition of 58% at 100 nM.
An antagonist of small conductance Ca2+‐activated K+ channels, apamin, concentration‐dependently inhibited the relaxation (58% at 1 μm).
Treatment with both K+ channel antagonists resulted in 84% inhibition of the EFS‐induced relaxation, which is comparable to the extent of inhibition induced by PACAP6–38 plus VIP10–28.
The inhibitory effect of VIP10–28 and of apamin, but not of charybdotoxin was additive: the same applied to PACAP6–38 and charybdotoxin, but not apamin.
Exogenously added VIP (100 nM‐1 μm) induced a slow gradual relaxation of the longitudinal muscle. Charybdotoxin, but not apamin significantly inhibited the VIP‐induced relaxation. VIP10–28, but not PACAP6–38 selectively inhibited the VIP‐induced relaxation.
Exogenously added PACAP (10–100 nM) also induced slow relaxation. Apamin and to a lesser extent, charybdotoxin, inhibited the PACAP‐induced relaxation. PACAP6–38, but not VIP10–28 selectively inhibited the PACAP‐induced relaxation.
Apamin at 100 nM inhibited inhibitory junction potentials (i.j.ps) induced by a single pulse of EFS. Apamin also inhibited a rapid phase, but not a delayed phase of i.j.ps induced by two pulses at 10 Hz. VIP10–28 did not inhibit i.j.ps induced by a single pulse, but significantly inhibited the delayed phase at two pulses. A combination of apamin and VIP10–28 abolished the i.j.ps induced by two pulses.
Both VIP and PACAP induced slow hyperpolarization of the cell membrane of the longitudinal muscle. Apamin inhibited the PACAP‐, but not VIP‐induced hyperpolarization.
From these findings it is suggested that VIP and PACAP are involved in NANC inhibitory responses of longitudinal muscle of the rat distal colon via activation of charybdotoxin‐ and apaminsensitive K+ channels, respectively.
Protection of low density lipoprotein oxidation at chemical and cellular level by the antioxidant drug dipyridamole
Authors: Iuliano L. , Colavita A.R. , Camastra C. , Bello V. , Quintarelli C. , Alessandroni M. , Piovella F. , Violi F. 
Published: July 2012

The oxidative modification of low density lipoprotein (LDL) is thought to be an important factor in the initiation and development of atherosclerosis. Natural and synthetic antioxidants have been shown to protect LDL from oxidation and to inhibit atherosclerosis development in animals. Synthetic antioxidants are currently being tested, by they are not necessarily safe for human use.
We have previously reported that dipyridamole, currently used in clinical practice, is a potent scavenger of free radicals. Thus, we tested whether dipyridamole could affect LDL oxidation at chemical and cellular level.
Chemically induced LDL oxidation was made by Cu(II), Cu(II) plus hydrogen peroxide or peroxyl radicals generated by thermolysis of 2,2′‐azo‐6/s(2‐amidino propane). Dipyridamole, (1–10 μm), inhibited LDL oxidation as monitored by diene formation, evolution of hydroperoxides and thiobarbituric acid reactive substances, apoprotein modification and by the fluorescence of cis‐parinaric acid.
The physiological relevance of the antioxidant activity was validated by experiments at the cellular level where dipyridamole inhibited endothelial cell‐mediated LDL oxidation, their degradation by monocytes, and cytotoxicity.
In comparison with ascorbic acid, α‐tocopherol and probucol, dipyridamole was the more efficient antioxidant with the following order of activity: dipyridamole > probucol > ascorbic acid > α‐tocopherol. The present study shows that dipyridamole inhibits oxidation of LDL at pharmacologically relevant concentrations. The inhibition of LDL oxidation is unequivocally confirmed by use of three different methods of chemical oxidation, by several methods of oxidation monitoring, and the pharmacological relevance is demonstrated by the superiority of dipyridamole over the naturally occurring antioxidants, ascorbic acid and α‐tocopherol and the synthetic antioxidant probucol.
Multiple mating by females is a natural outcome of a null model of mate encounters
Authors: Kokko Hanna , Mappes Johanna 
Published: July 2012

AbstractWhy do females of so many species mate multiply? The question makes use of an implicit null model that females by default should be monandrous and that polyandry requires an explanation. Here, we make the simple point that females encounter mates over their lifetime in a stochastic manner, and as they should accept at least one male, acceptance of all males may be a better null model than the more advanced strategy of accepting the first satisfactory one and rejecting all others. The advantage of this view is that it makes it explicit that females must accept and reject mates without precise knowledge of future mate encounters. In insects, for example, limitations of cognitive and sensory capabilities make it hard for females to compare many potential mates simultaneously. It is then not always possible for a female to be very choosy (i.e., to reject a large proportion of encounters) without simultaneously increasing the expected time spent as a virgin and decreasing the overall expected number of mates she accrues during her lifetime. We show that this fact easily leads to a pattern where choosiness is reduced and most females mate with more males than their optimal mate number. Our results suggest that monandry and polyandry may be less distinct strategies than they first appear as they may, to a large extent, reflect chance events influencing mate encounters. Polyandry can arise as a side effect of avoiding the risk of encountering too few acceptable mates – a viewpoint that is easily missed if females that have remained unmated are not included in datasets.
The Dialogue of Religious Experience: Theory and Practice
Authors: Friday John R. 
Published: July 2012

AbstractFor several decades the official teaching office of the Roman Catholic Church has consistently invoked the notion of religious experience as a category for interrelgious dialogue. Moreover, the Church has appealed to the so-called dialogue of religious experience as a means of encouraging its members to constructively engage with persons who are committed to ‘other’ religious traditions. This essay seeks to develop a systematic understanding of religious experience as well as the dialogue associated with it. Subsequent to summarizing the recent magisterial teaching on the dialogue of religious experience, the essay continues by probing the meaning of religious experience as such, particularly with the assistance of the theological insights of Bernard Lonergan and Louis Roy. The essay concludes by acknowledging some of the limitations that persist in connection with the dialogue of religious experience, namely, those that inevitably arise when considering the particularity of the incarnation and the necessity of the Church for salvation.
The Immobilization of Polyethylene Imine Nano and Microspheres on Glass Using High Intensity Ultrasound
Authors: Shimanovich Ulyana , Cavaco‐Paulo Artur , Gedanken Aharon 
Published: July 2012

The present article describes the creation and immobilization of Polyethylene imine (PEI) capsules on a glass surface. The synthesis and deposition were accomplished by short‐time (3 min) one‐step reaction. The preparation and immobilization of PEI spheres, was carried out using an environmental friendly method, the ultrasonic emulsification. The ultrasonic technique enables to control size and fulfillment of the internal part of the immobilized PEI spheres. Moreover, the ultrasonic emulsification method showed 100% efficiency in PEI spheres creation, which means no residues of aqueous PEI and oil solvents remained in the reaction flask after the nanosphere's creation. The immobilized PEI spheres have sizes varied from 50 to 500 nm. The PEI spheres were successfully filled either with organic solvent (hydrophobic) or with water (hydrophilic). This method provides us the perspective for future encapsulation of varies molecules which have hydrophobic or hydrophilic nature.
Fully Protected Glycosylated Zinc (II) Phthalocyanine Shows High Uptake and Photodynamic Cytotoxicity in MCF‐7 Cancer Cells
Authors: Kimani Stanley G. , Shmigol Tatiana A. , Hammond Samantha , Phillips James B. , Bruce James I. , MacRobert Alexander J. , Malakhov Mikhail V. , Golding Jon P. 
Published: July 2012

AbstractPhthalocyanine photosensitizers are effective in anticancer photodynamic therapy (PDT) but suffer from limited solubility, limited cellular uptake and limited selectivity for cancer cells. To improve these characteristics, we synthesized isopropylidene‐protected and partially deprotected tetra β‐glycosylated zinc (II) phthalocyanines and compared their uptake and accumulation kinetics, subcellular localization, in vitro photocytotoxicity and reactive oxygen species generation with those of disulfonated aluminum phthalocyanine. In MCF‐7 cancer cells, one of the compounds, zinc phthalocyanine {4}, demonstrated 10‐fold higher uptake, 5‐fold greater PDT‐induced cellular reactive oxygen species concentration and 2‐fold greater phototoxicity than equimolar (9 μm) disulfonated aluminum phthalocyanine. Thus, isopropylidene‐protected β‐glycosylation of phthalocyanines provides a simple method of improving the efficacy of PDT.
Neural Mechanisms of Rhythm Perception: Current Findings and Future Perspectives
Authors: Grahn Jessica A. 
Published: July 2012

AbstractPerception of temporal patterns is fundamental to normal hearing, speech, motor control, and music. Certain types of pattern understanding are unique to humans, such as musical rhythm. Although human responses to musical rhythm are universal, there is much we do not understand about how rhythm is processed in the brain. Here, I consider findings from research into basic timing mechanisms and models through to the neuroscience of rhythm and meter. A network of neural areas, including motor regions, is regularly implicated in basic timing as well as processing of musical rhythm. However, fractionating the specific roles of individual areas in this network has remained a challenge. Distinctions in activity patterns appear between “automatic” and “cognitively controlled” timing processes, but the perception of musical rhythm requires features of both automatic and controlled processes. In addition, many experimental manipulations rely on participants directing their attention toward or away from certain stimulus features, and measuring corresponding differences in neural activity. Many temporal features, however, are implicitly processed whether attended to or not, making it difficult to create controlled baseline conditions for experimental comparisons. The variety of stimuli, paradigms, and definitions can further complicate comparisons across domains or methodologies. Despite these challenges, the high level of interest and multitude of methodological approaches from different cognitive domains (including music, language, and motor learning) have yielded new insights and hold promise for future progress.