bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of cholinergic neurotransmission in guinea‐pig trachea by neuropeptide Y
Authors: Stretton C.D. , Barnes P.J. 
Published: July 2012

Neuropeptide Y (NPY) is localized to adrenergic nerves in guinea‐pig airways but its function is not known.
NPY (1 × 10−10‐3 × 10−7 m) had no direct effect on guinea‐pig tracheal smooth muscle in vitro.
NPY produced a concentration‐ and frequency‐dependent inhibition of the cholinergic component of responses elicited by electrical field stimulation (EFS) whilst having no effect on the contractile response to exogenously applied acetylcholine (ACh).
Yohimbine was able to reverse significantly the inhibitory effect of noradrenaline on the cholinergic component to EFS without having any significant effect on the inhibition produced by NPY.
Neither blockade of β‐adrenoceptors by propranolol, nor depletion of adrenergic nerves by incubation with 6‐hydroxydopamine caused any significant alteration in the response to EFS in the presence of 3 × 10−7 m NPY. Bretylium tosylate incubation to prevent noradrenaline release produced a small but significant enhancement of the inhibitory effect of NPY on EFS at high frequencies.
NPY appears to reduce the cholinergic component to EFS via a prejunctional mechanism, acting directly on receptors on cholinergic nerve terminals, rather than affecting adrenergic mechanisms. NPY released by adrenergic nerves may modulate cholinergic neurotransmission in guinea‐pig airways.
Development of non‐cholinergic, non‐adrenergic excitatory and inhibitory responses to intramural nerve stimulation in rat stomach
Authors: Ito Shigeo , Kimura Atsuko , Ohga Akira 
Published: July 2012

The onset and development of functional innervation of intramural neurones were examined by transmural nerve stimulation in circular muscle strips isolated from the rat stomach during the period from embryonic day (ED) 15 to 7‐days postnatal.
At ED 15, transmural stimulation elicited an atropine‐sensitive contraction in about half of the preparations. From ED 16, it caused a frequency‐dependent contraction in all preparations. Physostigmine significantly potentiated the amplitude of the nerve‐mediated contraction until ED 18.
Atropine inhibited but failed to abolish the contractile response to nerve stimulation in all preparations from ED 16.
During the contraction induced by carbamylcholine (CCh), transmural stimulation caused a biphasic response consisting of a contraction followed by a relaxation at ED 18 and ED 19, but caused a triphasic response consisting of a rapid relaxation followed by the biphasic response after birth.
CCh and substance P (SP) elicited contractions at ED 15 and vasoactive intestinal polypeptide (VIP) caused a relaxation at ED 16. The sensitivity to CCh and VIP increased with development but that to SP did not change.
The results suggest that functional intramural cholinergic and non‐cholinergic excitatory innervations in the rat stomach are established almost simultaneously by ED 16, and the onset of functional intramural non‐adrenergic inhibitory innervation lags about 2 days behind that of functional excitatory innervations.
Influence of epithelium on the responsiveness of guinea‐pig isolated trachea to adenosine
Authors: Advenier Charles , Devillier Philippe , Matran Régis , Naline Emmanuel 
Published: July 2012

The influence of epithelium removal on the effects of adenosine on airway contractility was investigated on the guinea‐pig isolated trachea.
In preparations under resting tone or precontracted with histamine 10−5 m, removal of the tracheal epithelium resulted in similar shifts to the left of the adenosine concentration‐response curves (0.61 ± 0.18 (P < 0.05) and 0.80 ± 0.09 (P < 0.001) log units; n = 5), corresponding to 4.07 and 6.31 fold potentiations of the relaxant effect of adenosine.
In the presence of dipyridamole 10−5 M the relaxant effects of adenosine were potentiated 85.1 fold on tracheae with epithelium; removal of the epithelium did not produce a significant additional shift to the left of the adenosine concentration‐response curves (0.07 ± 0.03 log units; n = 5; NS).
In the absence of dipyridamole, the theophylline‐adenosine antagonism was not of the competitive type, irrespective of whether the tracheae were with or without epithelium.
In the presence of dipyridamole, this antagonism was likely to be of the competitive type and its characteristics were the same when the epithelium was present or absent. Regression slope and pA2 values were 0.84 and 5.07, respectively, in the presence of epithelium and 0.76 and 4.89, respectively, in its absence.
It is suggested that, at least in the guinea‐pig isolated trachea model, the airway epithelium seems to be involved only in the uptake and metabolism of adenosine.
Spasmogen action in guinea‐pig isolated trachealis: involvement of membrane K+‐channels and the consequences of K+‐channel blockade
Authors: Boyle J.P. , Davies J.M. , Foster R.W. , Good D.M. , Kennedy I. , Small R.C. 
Published: July 2012

Acetylcholine (ACh), histamine, prostaglandin E2 and potassium chloride (KCl) each evoked concentration‐dependent spasm of guinea‐pig isolated trachealis treated with indomethacin (2.8 μm).
Neither tetraethylammonium (TEA; 0.1–10 mm) nor procaine (0.1–10 mm) potentiated these spasmogens. Indeed, procaine (10 mm) depressed the log concentration‐effect curves of all the spasmogens while TEA (1–10 mm) caused some depression of the log concentration‐effect curve of prostaglandin E2.
Intracellular electrophysiological recording was performed in trachealis bathed by normal Krebs solution or by Krebs solution containing 2.8 μm indomethacin. In either medium the majority of trachealis cells exhibited spontaneous electrical slow waves while some cells were electrically quiescent. In either medium the spasmogenic effects of ACh (1 mm) and histamine (0.2 mm) were accompanied by depolarization and abolition of slow wave discharge. In many cases the record of membrane potential subsequently exhibited noise which incorporated fast, hyperpolarizing transients.
In the absence and presence of indomethacin, TEA (10 mm) and procaine (5 mm) markedly reduced the membrane noise and hyperpolarizing transients evoked by ACh or histamine without augmenting the evoked tension.
It is concluded that slow wave discharge does not depend on prostaglandin synthesis. The membrane noise and hyperpolarizing transients evoked by ACh and histamine represent the opening of membrane K+‐channels. While such K+‐channel opening may offset spasmogen‐induced depolarization it does not moderate the evoked tension.
Effects of chronic oral administration of the antidepressants, desmethylimipramine and zimelidine on rat cortical GABAB binding sites: a comparison with 5‐HT2 binding site changes
Authors: Cross Jacqueline A. , Horton Roger W. 
Published: July 2012

The effects of chronic oral administration of desmethylimipramine (DMI) or zimelidine (1.25 and 5 mg kg−1 twice daily for 21 days) were studied on rat whole cortical γ‐aminobutyric acidB (GABAB) binding sites. No changes in receptor affinity or number were found with either drug.
A subsequent study of GABAB binding sites using higher doses of these drugs (5 and 10 mg kg−1) and rat frontal cortex was also without effect, when investigated 24 h after termination of drug administration or 72 h after DMI administration (5 mg kg−1).
The number of frontal cortical 5‐hydroxytryptamine2 (5‐HT2) binding sites was significantly and dose‐dependently decreased after both drugs, whereas the number of hippocampal 5‐HT2 binding sites was not significantly altered after either drug.
As the number of frontal cortical GABAB binding sites was unaltered whereas the number of 5‐HT2 binding sites was significantly decreased under identical study conditions, it may be concluded that the effects of antidepressant administration upon GABAB binding sites is a less consistent observation than their effects on 5‐HT2 binding sites.
Phentolamine lacks α2‐adrenoceptor agonist activity in anaesthetized dogs
Authors: Bell C. 
Published: July 2012

This study was performed in order to determine whether the blockade of sympathetic vasoconstriction in anaesthetized dogs by phentolamine is due to the antagonist action of the drug at postjunctional adrenoceptors, or is due to depression of neurotransmitter release by an agonist action at prejunctional adrenoceptors.
In dogs made areflexic by ganglion blockade with hexamethonium, phentolamine (0.5 mg i.a. or 0.5 mg kg−1 i.v.) elevated or did not affect femoral blood flow. By contrast, clonidine (0.5‐2.5 nmol, i.a.) produced femoral vasoconstriction, which was attenuated by prior administration of phentolamine.
Prior blockade of prejunctional α2‐adrenoceptors with yohimbine (30 μg kg−1, i.v.) did not reduce the blocking effect of phentolamine (0.5 mg kg−1, i.v.) on neurogenic vasoconstriction.
The results indicate that, in anaesthetized dogs, phentolamine lacks appreciable agonist activity at either prejunctional or postjunctional α2‐adrenoceptors. The blockade of neurogenic responses by phentolamine is therefore likely to be due to postjunctional adrenoceptor blockade.
Central inhibition by γ‐aminobutyric acid of the release of vasopressin by carbachol in the rat
Authors: Chowdrey H.S. , Bisset G.W. 
Published: July 2012

γ‐Aminobutyric acid (GABA) inhibited the antidiuretic response and the increased urinary excretion of vasopressin produced by carbachol when both drugs were injected into a lateral cerebral ventricle (i.c.v.) in the water‐loaded rat under ethanol anaesthesia.
The inhibitory effect of GABA was mimicked by muscimol and 3‐amino‐1‐propane sulphonic acid (3‐APS) and blocked by bicuculline.
GABA injected i.v. or into the cisterna magna (i.cist.) did not inhibit the release of vasopressin by carbachol injected i.c.v.
The results suggest a role for GABA as a putative inhibitory transmitter in the hypothalamo‐neurohypophysial system, acting directly on the supraoptic or paraventricular nuclei in the anterior hypothalamus.
Long‐term regulation of synaptic acetylcholine release and nicotinic transmission: the role of cyclic AMP
Authors: Briggs Clark A. , McAfee Donald A. , McCaman Richard E. 
Published: July 2012

Using the rat superior cervical ganglion in vitro, the relative efficacy of nicotinic synaptic transmission was estimated by recording the postganglionic compound action potential and the amount of endogenous acetylcholine (ACh) released. These two parameters were correlated in individual ganglia by sampling the bathing medium for the assay of ACh while simultaneously recording the postganglionic response.
The β‐adrenoceptor agonist isoprenaline potentiated both the evoked release of ACh and the postganglionic response by about 20% during preganglionic stimulation at 0.2 Hz.
The adenosine receptor agonist 2‐chloroadenosine inhibited ACh release and the postganglionic response by about 35%.
Tetanic preganglionic stimulation for a few seconds induced a long‐term potentiation of nicotinic responses and of ACh release. Both of these potentiations were dependent upon extracellular Ca2+ during the tetani.
Forskolin and analogues of cyclic AMP also caused a long‐lasting potentiation of both the evoked release of ACh and the postganglionic response, indicating that cyclic AMP may regulate transmission by a presynaptic mechanism. The specificity of the cyclic AMP analogues was tested using various butyryl‐ and bromo‐purine nucleotides.
The effects of forskolin and 8‐bromo‐cyclic AMP did not appear to be dependent upon extracellular Ca2+.
The potentiation caused by forskolin was consistently augmented by three phosphodiesterase inhibitors ‐ AH 21–132, papaverine and SQ 20‐006. However, the effect of forskolin was not consistently enhanced by theophylline, nor was it reduced by the adenylate cyclase inhibitor SQ 22–536.
The neurogenic long‐term potentiation was augmented by two of the phosphodiesterase inhibitors that also augmented the forskolin‐induced potentiation ‐ papaverine and SQ 20‐006.
It was concluded that cyclic AMP can enhance nicotinic transmission, and can do so by increasing the evoked release of ACh. However, it was not possible to prove that cyclic AMP mediates the long‐term potentiation induced by tetanic preganglionic stimulation.
Chronic prazosin attenuates the natriuretic response to a modest saline load in anaesthetized rats
Authors: Penner S. Brian , Smyth Donald D. 
Published: July 2012

The effect of chronic prazosin pretreatment (3 days) on the ability to excrete a modest saline load (i.v. saline, 0.097 ml min−1) was studied in the anaesthetized rat. Three days before the experiment, the drinking water was replaced with 0.5% dextrose (control), 0.015 mg ml−1 prazosin in 0.5% dextrose (low dose) or 0.15 mg ml−1 prazosin in 0.5% dextrose (high dose).
The selectivity of the prazosin for α1‐adrenoceptors was evaluated in pithed rats. The pressor response to phenylephrine was partially attenuated by the low dose of prazosin and completely attenuated by the high dose of prazosin. The pressor response to clonidine was slightly decreased by the 3 day prazosin pretreatment indicating a selectivity for α1‐adrenoceptors.
In rats pretreated with the low dose of prazosin, there was a significant decrease in sodium and water, but not potassium excretion as compared to the control group. Captopril failed to alter these effects of the low dose of prazosin. Blood pressure and creatinine clearance were the same in both groups. In rats pretreated with the high dose of prazosin, there was a further decrease in sodium and water but not potassium excretion. However, this dose of prazosin also significantly decreased blood pressure and increased creatinine clearance. A decrease in renal perfusion pressure with an aortic clamp to the same level as that observed with the high prazosin dose also decreased sodium and water but not potassium excretion. The decrease in sodium and water excretion was not as great as that observed with the high dose of prazosin.
The results indicate that chronic α1‐adrenoceptor blockade with prazosin attenuates the ability to excrete a saline load in a dose‐related manner. Whether this inability to excrete a saline load is analogous to the sodium and water retention observed with the clinical use of prazosin remains to be determined.
Effects of prolonged exposure to α,β‐methylene ATP on non‐adrenergic, non‐cholinergic excitatory transmission in the rectum of the chicken
Authors: Komori Seiichi , Kwon Seong‐Chun , Ohashi Hidenori 
Published: July 2012

Effects of prolonged exposure to α,β‐methylene ATP (α,β‐Me ATP) on contractions and excitatory junction potentials (e.j.ps) evoked by non‐adrenergic, non‐cholinergic (NANC) excitatory nerve stimulation have been investigated in the chicken isolated rectum and longitudinal muscle strip from chicken rectum pretreated with atropine (0.5 μm), methysergide (2 μ m) and pyrilamine (3 μm).
α,β‐Me ATP (20 nm‐4 μm) caused a rapid rise in tension of the longitudinal muscle of the isolated rectum preparation which returned to the baseline levels after a few minutes. The magnitude of the contractile response to NANC nerve stimulation was reduced after exposure to the drug. The inhibitory effect was related to the drug concentration; at 4 μm the nerve‐mediated contraction was abolished and frequently converted to a relaxation.
Adenosine 5′‐triphosphate (ATP, 100 μm), bovine neurotensin (2.5 nm) and K+‐rich solutions (30 mm and 60 mm) all produced a transient contraction of the isolated rectum preparation. The exposure to α,β‐Me ATP (0.2 and 4 μm) also rendered the preparation less sensitive to these stimulant substances.
α,β‐Me ATP (0.2 and 4 μm caused a membrane depolarization in cells of the longitudinal muscle strip. The depolarization reached a peak within 2–3 min after application and then decayed to a steady level that was still more positive than the baseline level. The electrotonic potentials were reduced in amplitude to 44 ± 8% (n = 7) of the normal amplitude if measured at the peak depolarization produced with 0.2 μm α,β‐Me ATP, and to 62 ± 10% (n = 7) if measured at the steady‐state depolarization. With 4 μm, the corresponding percentages were 33 ± 7% (n = 8) and 55 ± 7% (n = 8), indicating a decrease in membrane resistance.
The e.j.ps in response to field stimulation of the intramural nerves and Remak's nerve stimulation were decreased in amplitude and duration during exposure to α,β‐Me ATP (0.2 and 4 μm).
The smooth muscle cells regained normal membrane resistance and sensitivity to ATP on washout of α,β‐Me ATP (4 μm) more rapidly than the responses to NANC nerve stimulation.
It can be argued from the results that the suppression by α,β‐Me ATP of the contraction and e.j.p. evoked by NANC nerve stimulation in the chicken rectum, unlike the mammalian preparations described previously, is due mainly to a change in the electrical properties of the membrane of the smooth muscle cells, rather than being due, or only partly due, to desensitization of the purine receptor.
Interference of the Paf antagonist Ro 19–3704 with Paf and antigen‐induced bronchoconstriction in the guinea‐pig
Authors: Lagente Vincent , Desquand Stéphanie , Hadvary Paul , Cirino Maria , Lellouch‐Tubiana Arielle , Lefort Jean , Vargaftig B. Boris 
Published: July 2012

In vitro, Ro 19–3704, a structurally related antagonist of platelet‐activating factor (Paf) inhibited selectively rabbit platelet aggregation. In vivo, administered intravenously, it inhibited bronchoconstriction, leukopenia, thrombocytopenia and the accompanying accumulation of platelet aggregates in guinea‐pig lung microvessels induced by i.v. Paf. Administered by aerosol, Ro 19–3704 failed to inhibit bronchoconstriction, thrombocytopenia or leukopenia due to i.v. Paf.
Bronchoconstriction induced by Paf, in aerosol form, was blocked by Ro 19–3704 administered by the i.v. or aerosol route, which suggests that it interacts with pulmonary cells responsible for bronchoconstriction.
Ro 19–3704 has free radical scavenging properties, since it inhibited the production of superoxide anions by macrophages stimulated by Paf and by N‐formyl‐methionyl‐leucyl‐phenylalanine (FMLP). Ro 18–7715, another Paf antagonist and analogue of Ro 19–3704, failed to inhibit the production of superoxide anions by macrophages stimulated by FMLP at concentrations which were effective against Paf.
Administered intravenously, Ro 19–3704 failed to block bronchoconstriction induced by an i.v. injection of ovalbumin to guinea‐pigs passively sensitized with anti‐ovalbumin antiserum. Passive pulmonary anaphylaxis due to an aerosol of ovalbumin was blocked by i.v. Ro 19–3704.
Evidence for reduced β‐adrenoceptor coupling to adenylate cyclase in femoral arteries from spontaneously hypertensive rats
Authors: Asano Masahisa , Masuzawa Kaoru , Matsuda Tomohiro 
Published: July 2012

Arterial relaxant responses via β‐adrenoceptors have been demonstrated to be decreased in spontaneously hypertensive rats (SHR) when compared with normotensive Wistar‐Kyoto rats (WKY). To determine which process of the β‐adrenoceptor adenylate cyclase (AC) system is involved in the decreased responsiveness to β‐adrenoceptor stimulation, relaxant responses to forskolin and dibutyryl cyclic AMP (db cyclic AMP) were compared between strips of femoral and mesenteric arteries isolated from 13 week‐old SHR and age‐matched WKY.
The relaxant response to either forskolin, an activator of AC, or db cyclic AMP was not significantly different between the SHR and WKY, when the strips of both arteries from both strains were contracted with K+ to an equivalent magnitude (85% of the maximum).
Under the same conditions, however, the relaxant response to noradrenaline (NA) via β‐adrenoceptors was significantly decreased in the SHR arteries.
When the strips of femoral arteries were contracted with the same concentration of K+, there was a precontraction of greater magnitude in response to the K+ and a decreased relaxation in response to forskolin, db cyclic AMP or NA in the SHR. On the other hand, when the strips of mesenteric arteries were contracted with the same concentration of K+, the precontraction was smaller in magnitude and there was an increased relaxation in the SHR.
The relationship between the relaxant responses and the K+‐induced precontractions clearly showed that the ability of forskolin and NA to relax the K+‐contracted strips depends on the magnitude of precontraction. Therefore, a difference in magnitude of precontraction between the two groups may produce a meaningless difference.
The relaxant responses to forskolin and NA were significantly potentiated by the addition of isobutyl methylxanthine (IBMX), an inhibitor of cyclic AMP phosphodiesterase. Even in the presence of IBMX, relaxant responses to forskolin were the same for the two strains. The difference in the pD2 value for NA‐induced relaxation between the two strains was the same in the presence and absence of IBMX.
The relaxant effect of either nitroprusside or nifedipine, agents which are independent of this system, was not significantly different between the strips from SHR and WKY. These relaxations were not potentiated by IBMX.
From these results, it is concluded that the reduced β‐adrenoceptor coupling to AC is mainly involved in the decreased responsiveness to β‐adrenoceptor stimulation. Furthermore, for an accurate comparison to be made, it is necessary to minimize the influence of variations in the magnitude of precontraction on the relaxant responses.
On the adenosine receptor and adenosine inactivation at the rat diaphragm neuromuscular junction
Authors: Sebastião A.M. , Ribeiro J.A. 
Published: July 2012

The effects of adenosine and adenosine analogues 2‐chloroadenosine (CADO), l‐N6‐phenylisopropyladenosine (l‐PIA), d‐N6‐phenylisopropyladenosine (d‐PIA), N6‐cyclohexyladenosine (CHA) and 5′‐N‐ethylcarboxamide adenosine (NECA) on evoked endplate potentials (e.p.ps) and on twitch tension were investigated in innervated diaphragms of the rat.
Adenosine and its analogues decreased, in a concentration‐dependent manner, the amplitude of both the e.p.ps and the twitch responses evoked by nerve stimulation. The order of potency in decreasing the twitch tension was CHA, l‐PIA, NECA > d‐PIA > CADO > adenosine. l‐PIA was about 8 times more potent than d‐PIA. Neither adenosine nor the adenosine analogues affected the twitch responses of directly stimulated tubocurarine‐paralysed muscles.
8‐Phenyltheophylline (8‐PT), theophylline and isobutylmethylxanthine (IBMX), in concentrations virtually devoid of effect on neuromuscular transmission, antagonized the inhibitory effect of 2‐chloroadenosine. The order of potency of the alkylxanthines as antagonists of the adenosine receptor at the rat diaphragm neuromuscular junction was 8‐PT > IBMX > theophylline. The antagonism by these xanthines was shown to be competitive, the pA2 value for 8‐PT being 7.16. In concentrations slightly higher than those used to test its ability to antagonize the adenosine receptor, IBMX and 8‐PT increased the amplitude of e.p.ps without modifying their decay phase or the resting membrane potential of the muscle fibre.
The adenosine uptake inhibitor, nitrobenzylthioinosine (NBI) and the adenosine deaminase inhibitor, erythro‐9(2‐hydroxy‐3‐nonyl)adenine (EHNA), in concentrations virtually devoid of effect on neuromuscular transmission, potentiated the inhibitory effect of adenosine at the rat diaphragm neuromuscular junction. The potentiation factors were about 2.6 for NBI (5 μm), 2.2 for EHNA (25 μm) and 4.6 for the combination of NBI (5 μm) and EHNA (25 μm).
It is concluded that both uptake and deamination contribute to the inactivation of adenosine at the rat diaphragm neuromuscular junction and that in this preparation the inhibitory effect of adenosine on transmission is mediated by a xanthine‐sensitive adenosine receptor with an agonist profile which does not fit the criteria for its classification either as an A1 or A2‐adenosine receptor.