bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post‐receptor pathway of the ATP‐induced relaxation in smooth muscle of the mouse vas deferens
Authors: Gailly Ph. , Boland B. , Paques C. , Himpens B. , Casteels R. , Gillis J.M. 
Published: July 2012

The post‐receptor pathway of the ATP relaxant effect in K+‐precontracted vas deferens smooth muscle (VD) was examined.
The relaxation to ATP was not antagonized either by 10 μm methylene blue, a cyclic GMP inhibitor, by 10 μm indomethacin, an inhibitor of prostaglandin synthesis or by 100 μm NG‐nitro‐l‐arginine, an inhibitor of NO production.
The Rp‐diastereomer of adenosine 3′:5′‐cyclic monophosphorothioate (Rp‐cAMPS) 200 μm, a competitive inhibitor of cyclic AMP significantly diminished the relaxant response to ATP.
Isoprenaline 10 μm, a β‐adrenoceptor agonist, produced a sustained relaxation, inhibited by Rp‐cAMPS, without a significant change in [Ca2+]i, thereby mimicking the ATP‐induced relaxant effect.
The level of the phosphorylated myosin light chain in the precontracted VD was significantly lowered by 1000 μm ATP.
ATP (1000 μm) and isoprenaline (10 μm) produced the same increase (+ 50%) of [cyclic AMP] when applied to a resting VD.
The effect of simultaneous increases of [Ca2+]i and of [cyclic AMP] produced by externally applied ATP are discussed.
These results suggest that ATP‐induced relaxation in K+‐precontracted VD is mediated by the activation of adenylyl cyclase.
Evidence for sympathetic neurotransmission through presynaptic N‐type calcium channels in human saphenous vein
Authors: Fabi Fulvia , Chiavarelli Mario , Argiolas Livio , Chiavarelli Roberto , del Basso Paola 
Published: July 2012

The specific type(s) of voltage‐sensitive calcium channels (VSCCs) involved in sympathetic neurotransmission have not yet been characterized in human vascular tissues. We therefore examined the functional role of the N‐ and L‐type VSCCs in human saphenous veins.
Contractile response curves for transmural nerve stimulation (TNS) and for exogenously administered noradrenaline (NA) were obtained in superfused saphenous vein rings. The contractions induced by TNS, but not by NA, were inhibited by 1 μm tetrodotoxin and by 10 μm guanethidine. Both responses were substantially reduced by 1 μm phentolamine, indicating that the contractions evoked by TNS were mediated by endogenous NA released from noradrenergic nerves.
In the presence of 2 μm ω‐conotoxin GVIA (omega Conus Geographus toxin, fraction VI A; ω‐CgTx), a polypeptide with specific inhibitory activity on N‐ and L‐type calcium channels, the neurally evoked contractions were almost completely abolished. In contrast, the responses induced by exogenous NA were not affected by the neurotoxin, thus providing evidence of the exclusive presynaptic action of ω‐CgTx.
In the presence of the calcium antagonist verapamil (10 μm), which selectively blocks L‐type VSCCs, the contractions induced by both TNS and NA were diminished to the same extent, suggesting that the organic calcium blocker is active only at the postjunctional level.
It is concluded that N‐type calcium channels are the main pathway of calcium entry controlling the functional responses induced by activating sympathetic nerves; the role of L‐type channels appears to be limited to the postjunctional level, modulating smooth muscle contractions.
The effect of ions and second messengers on long‐term potentiation of chemical transmission in avian ciliary ganglia
Authors: Scott T.R.D. , Bennett M.R. 
Published: July 2012

The effects of tetanic stimulation of the oculomotor nerve on transmission through the avian ciliary ganglion have been determined by use of the amplitude of the compound action potential recorded in the ciliary nerve, in the presence of hexamethonium (300 μm), as a measure of synaptic efficacy.
Tetanic stimulation for 20 s at 30 Hz potentiated the chemical phase of the compound action potential by at least 100% of its control level. This potentiation, reflecting an increase in synaptic efficacy, decayed over two distinct time courses: firstly, a rapid decay with a time constant in the order of minutes, and secondly, a slower decay, representing a smaller potentiation, with a time constant in the order of an hour. The large increase in synaptic efficacy is attributed to post‐tetanic potentiation (PTP) whereas the smaller but longer lasting increase is attributed to long‐term potentiation (LTP).
Higher frequencies of tetanic stimulation gave increased PTP and LTP.
In order to test whether the influx of calcium ions into the nerve terminal during the tetanus is likely to be involved in potentiation, facilitation was measured during PTP and LTP. Facilitation was reduced to approximately zero during PTP but recovered to normal values about 15 min into LTP. A requirement for the induction of LTP was shown to be the presence of calcium in the bathing solution. However, blocking synaptic transmission with a high concentration of hexamethonium (3 mm) during the tetanic stimulation did not block the induction of LTP.
Application of the muscarinic inhibitor, atropine (2 μm), did not affect the magnitude of PTP or LTP.
The activator of protein kinase C, phorbol 12,13‐dibutyrate (2 μm) potentiated synaptic transmission and reduced the potentiation due to PTP although it did not affect that due to LTP, but the inhibitor of this kinase, staurosporine (0.5 μm), partially blocked the appearance of LTP without affecting PTP after the tetanus.
An inhibitor of calmodulin, W‐7 (5 μm), reversibly blocked the appearance of LTP significantly after a tetanus although the size of PTP was not affected.
The results presented here suggest that the initiation of LTP in the ciliary ganglion is due to an influx of calcium ions into the calyciform nerve terminal during the tetanus and that the mechanism for LTP involves a calcium‐calmodulin‐dependent process.
The paradoxical vascular interactions between endothelin‐1 and calcitonin gene‐related peptide in the rat gastric mucosal microcirculation
Authors: Lopez‐Belmonte J. , Whittle B.J.R. 
Published: July 2012

The interactions between local intra‐arterial infusion of endothelin‐1 (ET‐1) and rat α‐calcitonin gene‐related peptide (α‐CGRP) on gastric mucosal damage and blood flow have been investigated in the pentobarbitone‐anaesthetized rat.
Close‐arterial infusion of ET‐1 (2–200 pmol kg−1 min−1) induced a significant and dose‐dependent increase in gastric mucosal haemorrhagic injury.
Close‐arterial infusion of the higher doses of ET‐1 (100 and 200 pmol kg−1 min−1) resulted in a biphasic effect on mucosal blood flow, as determined by laser Doppler flowmetry (LDF). This consisted of an initial transient increase followed by a pronounced and sustained fall in LDF.
Local microvascular constriction may thus contribute to the mechanisms underlying the gastric injury induced by these higher doses of ET‐1.
However, close‐arterial infusion of lower doses of ET‐1 (2–50 pmol kg−1 min−1), that also provoked substantial mucosal damage, induced only a sustained and significant mucosal hyperaemia, which may be secondary to microvascular injury.
Concurrent close‐arterial administration of rat α‐CGRP (50 pmol kg−1 min−1) significantly inhibited the extent of gastric mucosal injury induced by ET‐1 (5 pmol kg−1 min−1).
Furthermore, concurrent close‐arterial infusion of this dose of α‐CGRP, which itself increased mucosal LDF, significantly inhibited the hyperaemic response induced by close‐arterial infusion of ET‐1 (5 pmol kg−1 min−1).
These results indicate a damaging action on the gastric mucosa by low doses of ET‐1 which is independent of local vasoconstriction, that may involve a direct injury of the microvascular endothelium. The protective action of α‐CGRP thus seems unlikely to be due to a local vasodilator effect but may reflect protective actions on the microvascular endothelium
Effects of ω‐conotoxin on adrenergic, cholinergic and NANC neurotransmission in the rabbit urethra and detrusor
Authors: Zygmunt P.M. , Zygmunt P.K.E. , Högestätt E.D. , Andersson K.‐E. 
Published: July 2012

The effects of ω‐conotoxin GVIA (an inhibitor of N‐type voltage‐operated calcium channels; VOCCs) were compared on adrenergic, cholinergic and non‐adrenergic, non‐cholinergic (NANC) responses induced by electrical field stimulation (EFS) in the rabbit urethra and detrusor.
EFS induced a relaxation in urethral smooth muscle and lamina propria precontracted by arginine vasopressin (AVP). The relaxation was abolished by tetrodotoxin (TTX) or the nitric oxide (NO) synthase inhibitor Nω‐nitro‐l‐arginine. ω‐Conotoxin inhibited the relaxation induced by EFS, but not that elicited by the NO donor 3‐morpholino‐sydnonimin. The inhibition, however, decreased with increasing frequencies of stimulation. Nimodipine, tetramethrin and nickel did not affect the ω‐conotoxin‐resistant relaxation in lamina propria, suggesting that neuronal L or T VOCCs were not involved in the response.
EFS contracted urethral smooth muscle at resting tension. The contractions were virtually abolished by TTX or prazosin. ω‐Conotoxin effectively inhibited the contractile responses to EFS, but not those to exogenous noradrenaline. An ω‐conotoxin‐resistant contraction was, however, observed at high frequencies of stimulation.
The detrusor responded with frequency‐dependent contractions upon EFS. A TTX‐resistant contraction less than 10% of controls remained at 30 Hz stimulation. At a stimulation frequency of 10 Hz, scopolamine reduced the EFS‐induced contraction by 71%. ω‐Conotoxin inhibited the responses in both the absence and presence of scopolamine. The inhibition decreased with increasing frequencies of stimulation (examined in the absence of scopolamine). ω‐Conotoxin did not affect the contractile responses to carbachol or adenosine 5′‐triphosphate.
The adrenergic contraction (25 Hz) and NANC relaxation (10 Hz) in the urethra, and cholinergic and NANC contractions (10 Hz) in the detrusor were inhibited concentration‐dependently by ω‐conotoxin. The adrenergic contraction in the urethra was 10 times and the cholinergic contraction in the detrusor was three times more sensitive to ω‐conotoxin than the NANC responses.
These results suggest that NANC neurotransmission is less inhibited by ω‐conotoxin than transmission mediated by adrenergic and cholinergic nerves in the rabbit lower urinary tract. In the urethra a marked ω‐conotoxin‐resistant component of the NANC relaxation was observed which increased with increasing stimulation frequencies and was unaffected by inhibitors of L and T type VOCCs. This raises the question whether VOCCs of a type other than L, T, and N is involved in the mediation of this response.
The action of Hoe 140 on the bradykinin‐induced splenic pressor reflex of the anaesthetized cat
Authors: Louttit J.B. , Coleman R.A. 
Published: July 2012

Intrasplenic injection of bradykinin (BK) induced a dose‐dependent pressor response in the anaesthetized cat, with an ED50 of 0.98 ± 0.43 nmol. In contrast, intrasplenic administration of desArg9bradykinin (desArg9K) was without significant effect at doses of up to 200 nmol.
Intravenously administered BK induced a dose‐dependent depressor response in the anaesthetized cat, with an ED50 of 0.86 ± 0.09 nmol kg−1. desArg9BK was again without significant effect in this system at doses of up to 200 nmol kg−1.
Both the pressor and depressor responses to BK were antagonized to a similar degree in a dose‐dependent manner by Hoe 140 (10 and 100 nmol kg−1, i.v.).
At these doses, Hoe 140 appears to be a specific BK antagonist as it was ineffective against pressor responses to intrasplenic injection of capsaicin (5 nmol), while blocking those to an approximately equieffective dose of BK (1 nmol) in a dose‐dependent fashion.
Both the pressor response to intrasplenic BK and the depressor response to intravenous BK in the anaesthetized cat appear to be mediated by B2‐receptors. This model may be useful in the quantitative determination of the antinociceptive potency of BK antagonists.
Inhibition by hydrochlorothiazide of insulin release and calcium influx in mouse pancreatic β‐cells
Authors: Sandström Per‐Erik 
Published: July 2012

The effect of hydrochlorothiazide on insulin release, 36Cl− fluxes and 45Ca2+ uptake was tested in β‐cell‐rich mouse pancreatic islets.
At high glucose concentrations (10 and 20 mmol l−1), low concentrations of hydrochlorothiazide (0.1–1.0 μmol l−1) reduced insulin release by 22–42%. At lower glucose concentrations (3–8.5 mmol l−1) insulin release was not affected by the drug.
Neither short‐term influx (3 min) nor net accumulation (60 min) of 36Cl− in the islets was affected by hydrochlorothiazide (0.1–500 μmol l−1).
Glucose‐stimulated 45Ca2+ uptake was significantly reduced by hydrochlorothiazide (1–10 μmol l−1).
The data suggest that the diabetogenic effect of hydrochlorothiazide, at least in part, can be mediated by direct inhibition of insulin release from the pancreatic β‐cells. The inhibition is not mediated by reduced chloride fluxes but may rather be caused by inhibition of calcium uptake.
Effects of atrial natriuretic peptide and nitroprusside on isolated pulmonary resistance and conduit arteries from rats with pulmonary hypertension
Authors: Wanstall Janet C. , Thompson Justine S. , Morice Alyn H. 
Published: July 2012

The relaxant effects of atrial natriuretic peptide (ANP) and nitroprusside were studied on prostaglandin F2α (PGF2α)‐contracted preparations of pulmonary resistance vessels (internal diameter 200–500 μm) and main pulmonary arteries taken from rats with pulmonary hypertension induced by monocrotaline (105 mg kg−1, s.c., 4 weeks previously). Control rats received saline.
In preparations from monocrotaline‐treated rats, the potencies (negative log EC50) of ANP on resistance vessels (8.45) and main pulmonary arteries (8.25) were similar to those obtained in vessels from control rats (8.78 and 8.53 respectively), whereas those of nitroprusside were significantly less than in controls in both resistance vessels (7.13 compared with 7.63 in controls; three fold decrease in potency) and main pulmonary arteries (6.92 compared with 8.17 in controls; 18 fold decrease in potency).
On pulmonary resistance vessels from monocrotaline‐treated rats, the maximum relaxant responses to ANP and nitroprusside, and also to pinacidil, were increased compared with controls, and reversal of the PGF2α‐induced contraction by these drugs was greater than 100%. In contrast, on main pulmonary arteries from monocrotaline‐treated rats, the maximum relaxations to ANP and nitroprusside were not increased relative to controls, and reversal of PGF2α was not greater than 100%.
Since the high potency of ANP on pulmonary resistance and conduit arteries is retained in vessels from rats with pulmonary hypertension, whether induced by monocrotaline (this study) or by chronic hypoxia (previous findings), it is postulated that elevation of plasma levels of ANP by use of drugs that inhibit the breakdown of this endogenous peptide, may be one approach to the pharmacological treatment of pulmonary hypertension.
Comparison of haemoconcentration induced by big endothelin‐1 and endothelin‐1 in mice
Authors: Okumura Hiroshi , Ashizawa Naoki , Kobayashi Fujio , Arai Koshi , Asakura Rieko , Ashikawa Nami , Matsuura Akihiro 
Published: July 2012

The profile of haemoconcentration induced by big endothelin‐1 (big ET‐1), a precursor of endothelin‐1 (ET‐1), was compared with that induced by endothelin‐1 in mice.
ET‐1(1.5 nmol kg−1, i.v.) increased haematocrit in mice, which reached a maximum at 5 min and then returned to the control value within 30 min after the administration, this occurred at the same time as changes in the plasma immunoreactive endothelin‐1 and rat atrial natriuretic peptide (rANP)‐like activities (IR‐ET‐1 and IR‐rANP, respectively).
Big ET‐1(2.5–15 nmol kg−1, i.v.) also caused a significant and dose‐dependent increase in haematocrit, that lasted over 3 h although elevated plasma IR‐ET‐1 and IR‐rANP had almost been restored to the initial levels within 10 min after big ET‐1 injection.
A metalloproteinase inhibitor, phosphoramidon (10 mg kg−1, i.v.), which inhibits the activity of endothelin converting enzyme (ECE), delayed the onset of big ET‐1‐induced haemoconcentration, but failed to alter the maximal value and the duration of the haemoconcentration.
Pretreatment with phosphoramidon (10 mg kg−1, i.v.) did not affect the big ET‐1‐induced change in plasma IR‐ET‐1, while significant delay of the disappearance of plasma IR‐rANP and significant suppression of a sustained increase in tissue IR‐ET‐1 were observed.
These results suggest that ET‐1, not in plasma but in tissue, plays an important role in the pathogenesis of big ET‐1‐induced long‐lasting haemoconcentration, in which unknown factors besides rANP are involved.
Pharmacological characterization of the metabotropic glutamate receptor inhibiting d‐[3H]‐aspartate output in rat striatum
Authors: Lombardi Grazia , Alesiani Marina , Leonardi Patrizia , Cherici Giovanna , Pellicciari Roberto , Moroni Flavio 
Published: July 2012

The effects of several agonists of the metabotropic glutamate receptor (mGluR) were studied in adult rat striatal slices by measuring (i) KCl (30 mm)‐induced output of previously taken up d‐[3H]‐aspartate (Asp), (ii) forskolin (30 μm)‐induced adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) accumulation and (iii) phophoinositide (PI) hydrolysis.
K+‐induced efflux of d‐[3H]‐Asp was inhibited by the following mGluR agonists: (1S,3S,4S)‐(carboxycyclopropyl)glycine (l‐CCG‐I), (1S,3R)‐1‐aminocyclopentane‐1,3‐dicarboxylic acid (1S,3R‐ACPD) and quisqualic acid (Quis). 2‐Amino‐4‐phosphonobutyrate (l‐AP4) was inactive up to 300 μm. The maximal inhibition of d‐[3H]‐Asp output was 60 ± 8%. The EC50s of mGluR agonists were: 0.5 μm for l‐CCG‐I, 100 μm for 1S,3R‐ACPD and 100 μm for Quis.
Forskolin‐induced cyclic AMP accumulation was also inhibited by mGluR agonists. The maximal inhibition was 50 ± 4% and was obtained at a concentration of 10 μm for l‐CCG‐I and 100 μm for 1S,3R‐ACPD. The EC50s for this inhibition were: 0.9 μm for l‐CCG‐I and 20 μm for 1S,3R‐ACPD. Quis (300 μm) inhibited cyclic AMP accumulation by approximately 20%. l‐AP4 slightly potentiated cyclic AMP accumulation.
PI hydrolysis was stimulated by mGluR agonists. The most potent compound was Quis (100 μm), which increased inositol phosphate formation up to 2.2 fold over control values. Its EC50 was 15 μm.l‐CCG‐I and 1S,3R‐ACPD increased inositol phosphate formation by approximately 1.8 fold and their EC50 values were 30 and 25 μm, respectively. l‐AP4 did not affect PI hydrolysis.
In conclusion, mGluR agonists that reduce d‐[3H]‐Asp output have a pharmacological profile similar to that of mGluR agonists inhibiting cyclic AMP accumulation. l‐CCG‐I appears to be a relatively selective agonist for the mGluR receptor which inhibits d‐[3H]‐Asp efflux and cyclic AMP accumulation, while Quis appears to act preferentially on the mGluR receptor linked to the metabolism of PIs.
Prejunctional modulation of noradrenaline release in mouse and rat vas deferens: contribution of P1‐ and P2‐purinoceptors
Authors: Kurz Katharina , von Kügelgen Ivar , Starke Klaus 
Published: July 2012

Prejunctional purinoceptors modulating the release of noradrenaline were compared in mouse and rat vas deferens. Tissue slices were preincubated with [3H]‐noradrenaline and then superfused and stimulated electrically, in most experiments by trains of 60 pulses, 1 Hz.
In mouse vas deferens, 2‐chloroadenosine (IC50 0.24 μm), β,γ‐methylene‐ATP (IC50 3.8 μm), α,β‐methylene‐ATP (IC50 2.9 μm) and 2‐methylthio‐ATP (only 30 μm tested) reduced the evoked overflow of tritium. 8‐Cyclopentyl‐1,3‐dipropylxanthine (DPCPX), 10 nm, antagonized the effect of 2‐chloroadenosine (apparent pKB 10.2) as well as of β,γ‐methylene‐ATP (apparent pKB 9.6) and α,β‐methylene‐ATP. Suramin, 300 μm, attenuated the effect of 2‐chloroadenosine at best very slightly, antagonized the effect of β,γ‐methylene‐ATP (apparent pKB 4.5) and, when combined with DPCPX 10 nm, caused a further marked shift to the right of the concentration‐response curve of β,γ‐methylene‐ATP beyond the shift produced by DPCPX alone.
In rat vas deferens, 2‐chloroadenosine (IC50 0.20 μm), β,γ‐methylene‐ATP (IC50 4.8 μm); α,β‐methylene‐ATP (IC50 3.0 μm) and 2‐methylthio‐ATP (only 30 μm tested) also reduced the evoked overflow of tritium. DPCPX, 10 nm, antagonized the effect of 2‐chloroadenosine (apparent pKB 9.7) as well as of β,γ‐methylene‐ATP (apparent pKB 9.6) and α,β‐methylene‐ATP. Suramin, 300 μm, did not change the effect of 2‐chloroadenosine, attenuated the effect of β,γ‐methylene‐ATP at best very slightly and, when combined with DPCPX, caused at best a very small shift to the right of the concentration‐response curve of β,γ‐methylene‐ATP beyond the shift produced by DPCPX alone.
It is concluded that prejunctional purinoceptor mechanisms in mouse and rat vas deferens are similar. In either species, both nucleosides such as adenosine and nucleotides such as β,γ‐methylene‐ATP activate a common release‐inhibiting receptor which is a P1‐ or, more specifically, A1‐purinoceptor. There seems to be no need to postulate the existence of a novel prejunctional P3‐purinoceptor. Moreover, the sympathetic terminal axons possess an additional P2‐purinoceptor in both species which is activated by some nucleotides such as β,γ‐methylene‐ATP and 2‐methylthio‐ATP, although the activation of the P2‐purinoceptor by β,γ‐methylene‐ATP is difficult to demonstrate in the rat.
PPADS selectively antagonizes P2X‐purinoceptor‐mediated responses in the rabbit urinary bladder
Authors: Ziganshin Airat U. , Hoyle Charles H.V. , Bo Xuenong , Lambrecht Günter , Mutschler Ernst , Bäumert Hans G. , Burnstock Geoffrey 
Published: July 2012

Pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS), an inhibitor of P2X‐purinoceptor‐mediated responses in rabbit vas deferens, was investigated for its ability to antagonize contractions evoked by α,β‐methylene ATP (α,β‐MeATP), carbachol and electrical field stimulation in the rabbit urinary bladder detrusor muscle.
PPADS (1–30 μm) caused concentration‐dependent inhibition of contractions to the stable P2X‐purinoceptor agonist, α,β‐MeATP, decreasing the maximum response to α,β‐MeATP (30 μm) at concentrations of 3–30 μm. The pD2 value for α,β‐MeATP in the absence of PPADS was 6.52 ± 0.10 (8). In the presence of PPADS at concentrations of 1, 3, 10 and 30 μm the negative log concentrations of α,β‐MeATP that cause the same contractile response as the pD2 value were significantly different from control, being respectively 6.17 ± 0.09 (8), 5.64 ± 0.12 (7), 5.15 ± 0.23 (7) and 4.78 ± 0.22 (5).
PPADS (1–30 μm) caused concentration‐dependent inhibition of contractions to stimulation of intramural purinergic nerves (1–32 Hz). There was a greater inhibition at lower frequencies (1–8 Hz) than at higher frequencies (16–32 Hz). PPADS, 30 μm, did not produce significantly greater antagonism than 10 μm.
PPADS (30 μm) had no significant influence on the contractile potency of carbachol: the pD2 values of carbachol in the absence and presence of PPADS were not significantly different being 6.42 ± 0.16 (5) and 6.33 ± 0.18 (5), respectively. However, PPADS caused a small, but significant, suppression of the maximal response of carbachol, reducing it by approximately 9%.
Radioligand binding studies carried out on rabbit bladder membranes with [3H]‐α,β‐methylene ATP ([3H]‐α,β‐MeATP) showed that PPADS concentration‐dependently inhibited the binding of [3H]‐α,β‐MeATP to P2X‐purinoceptors, while the binding of [3H]‐quinuclidinyl benzilate to muscarinic cholinoceptors was not affected.
Thus, PPADS (1–30 μm) antagonized responses mediated via P2X‐purinoceptors in the rabbit urinary bladder. It was selective for P2‐purinoceptor‐mediated contractions rather than those mediated via muscarinic receptors. Binding studies demonstrated that the antagonistic effect of PPADS is via a direct interaction with P2X‐purinoceptors.