bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of peptide histidine isoleucine and neuropeptide Y on mucus volume output from the ferret trachea
Authors: Webber S.E. 
Published: July 2012

The effects of peptide histidine isoleucine (PHI) and neuropeptide Y (NPY) were examined on the mucus volume output produced by methacholine and phenylephrine in the ferret whole trachea in vitro.
Sustained application of methacholine (5 μM) or phenylephrine (20 μM) produced a maintained volume output of mucus from the trachea. Both these agonists also increased the output of lysozyme (a marker for serous cell secretion).
PHI inhibited the maintained mucus volume output produced by methacholine but had no effect on that due to phenylephrine. The output of lysozyme produced by methacholine or phenylephrine was not significantly changed by PHI.
NPY enhanced the volume output of mucus produced by methacholine or phenylephrine; however, the rate of output of lysozyme in mucus produced by both agonists was reduced by NPY.
We suggest that PHI has no effect on serous cell secretion but inhibits secretion from another source, possibly mucous cells. NPY inhibits serous cell secretion but has a stronger stimulant action on secretion from another source, again possibly mucous cells.
PHI and NPY may be important physiological modulators of mucus volume output in the ferret trachea.
Amiloride analogues cause endothelium‐dependent relaxation in the canine coronary artery in vitro: possible role of Na+/Ca2+ exchange
Authors: Cocks T.M. , Little P.J. , Angus J.A. , Cragoe E.J. 
Published: July 2012

A number of amiloride analogues were used to test the proposal that Na+/Ca2+ exchange may play a role in the secretion of endothelium‐derived relaxing factor (EDRF). The analogues used were those substituted on either the 5‐amino group or the terminal guanidino nitrogen atom. The former block both Na+ /Ca2+ and Na+ /H+ exchange whilst the latter block the Na+ channel and the Na+ /Ca2+ exchange.
Both series of compounds caused relaxation in isolated rings of dog coronary artery (EC50 values, 1–10 μM) presumably due to release of EDRF since removal of endothelium greatly attenuated the response.
Amiloride (1–100 μM) had little effect on either endothelium‐intact or denuded arteries.
The guanidino substituted analogues also appeared to block selectively the relaxation response to acetylcholine in the coronary artery, independently of their EDRF‐releasing activity.
It is proposed that endothelial cells have an active Na+ /Ca2+ exchange operating in the forward mode to extrude Ca2+. This mechanism may be important in the control of EDRF release.
Effects of ethanol and pantothenic acid on brain acetylcholine synthesis
Authors: Rivera‐Calimlim Leonor , Hartley Donna , Osterhout Donna 
Published: July 2012

Measurements of brain acetylcholine (ACh) synthesis from precursor [14 C]‐pyruvate, pantothenic acid (PA) concentration in the brain, and blood ethanol (EtOH) concentration were made in rats treated with either ethanol (5–6 g kg−1 body wt daily) alone or ethanol with PA supplementation (100–200 mg kg−1 body wt daily). EtOH with or without PA was administered orally by either Lieber‐Decarli liquid diet for 4 weeks and 4 months or by oral intubation for 1 and 4 days. Matched controls were given either ethanol‐free liquid diet or saline.
ACh synthesis in the brain of rats treated with ethanol alone for 4 months was significantly (P < 0.01) inhibited. PA concentration of the brain was diminished to 7.0% of the control value.
PA concentration in the brain of rats treated with ethanol plus PA for 4 months was three times that of rats treated with ethanol alone. ACh synthesis in rats with ethanol and PA supplementation was also significantly (P <0.01) higher.
There was no difference in blood EtOH concentration between rats treated with ethanol with or without PA supplement.
The EtOH effect on ACh synthesis and PA concentration in the brain was observed in the chronic treatments but not in the acute treatments.
Data suggest that chronic ethanol exposure may decrease ACh synthesis by depleting PA, a precursor for the synthesis of acetyl CoA. Acetyl CoA is an essential substrate for ACh synthesis.
Characterization of neuropeptide‐induced histamine release from human dispersed skin mast cells
Authors: Lowman Mark A. , Benyon R. Christopher , Church Martin K. 
Published: July 2012

Human skin mast cells, unlike other human mast cells so far studied, released histamine in a concentration‐related manner in response to substance P, vasoactive intestinal peptide (VIP) and somatostatin (1 μM to 30 μM). In contrast, eledoisin, physalaemin, neurokinin A, neurokinin B, calcitonin gene‐related peptide (CGRP), neurotensin, bradykinin and Lys‐bradykinin induced negligible histamine release.
The low histamine releasing activity of physalaemin, eledoisin, neurokinin A and neurokinin B relative to substance P suggests that the human skin mast cell activation site is distinct from the tachykinin NK‐1, NK‐2 or NK‐3 receptors described in smooth muscle.
The relative potencies of substance P and its fragments SP2–11, SP3–11, SP4–11 and SP1–4 in releasing histamine from human skin mast cells suggests that both the basic N‐terminal amino acids and the lipophilic C‐terminal portion of substance P are essential for activity.
Peptide‐induced histamine release, like that induced by compound 48/80, morphine and poly‐L‐lysine, is rapid, reaching completion in 10–20 s, is largely independent of extracellular calcium but requires intact glycolysis and oxidative phosphorylation.
The substance P analogue, [D‐Pro4, D‐Trp7,9,10] SP4–11 (SPA), not only reduced substance P‐induced histamine release in a concentration‐related manner but also inhibited that induced by VIP, somatostatin, compound 48/80, poly‐L‐lysine and morphine but not anti‐IgE.
The similar characteristics of histamine release induced by substance P, VIP, somatostatin, compound 48/80, poly‐L‐lysine and morphine suggest that they share a common pathway of activation‐secretion coupling distinct from that of IgE‐dependent activation. Furthermore, the ability of human skin mast cells to respond to basic non‐immunological stimuli including neuropeptides may reflect a specialised function for these cells.
Regional haemodynamic effects of depressor neuropeptides in conscious, unrestrained, Long Evans and Brattleboro rats
Authors: Gardiner Sheila M. , Compton Alix M. , Bennett Terence 
Published: July 2012

The regional haemodynamic effects of i.v. bolus doses of atrial natriuretic peptide (ANP, 1 and 10 nmol), calcitonin gene‐related peptide (CGRP, 0.05 and 0.5 nmol) and corticotropin‐releasing factor (CRF, 1 and 5 nmol) were assessed in conscious Long Evans and Brattleboro rats chronically instrumented with miniaturized, pulsed Doppler probes.
The low dose of ANP was without effect on mean arterial pressure (MAP), but caused tachycardia and hindquarters vasodilatation with vasoconstriction in renal and mesenteric beds in Long Evans rats. With the high doses of ANP these effects were more pronounced and MAP fell. In Brattleboro rats there was a primary renal vasodilatation.
The low dose of CGRP caused a slight fall in MAP in Long Evans rats, tachycardia and a renal vasodilatation. The high dose of CGRP caused marked hypotension, tachycardia and renal, mesenteric and hindquarters vasodilatation in both strains of rat. However, only in Long Evans rats were there secondary renal and mesenteric vasoconstrictions.
The low dose of CRF caused falls in MAP in both strains of rat, accompanied by renal and, particularly, mesenteric vasodilatation. Administration of the high dose of CRF caused profound, prolonged hypotension, tachycardia and mesenteric vasodilatation. There was also (late onset) hindquarters vasodilatation accompanying renal vasoconstriction that followed the initial vasodilatation in this vascular bed.
These results indicate that appropriate doses of particular peptides may be capable of promoting flow through individual peripheral vascular beds.
The action of volatile anaesthetics on stimulus‐secretion coupling in bovine adrenal chromaffin cells
Authors: Pocock G. , Richards C.D. 
Published: July 2012

The action of four volatile anaesthetics, ethrane, halothane, isoflurane and methoxyflurane on stimulus‐secretion coupling has been studied in isolated bovine adrenal medullary cells. All four agents inhibited the secretion of adrenaline and noradrenaline evoked by 500 μM carbachol at concentrations within the anaesthetic range. Total catecholamine secretion induced by stimulation with 77 mM potassium was also inhibited but at higher concentrations. All four agents inhibited the45 Ca influx evoked by stimulation with 500 μM carbachol and the45 Ca influx in response to K+‐depolarization.
When total catecholamine secretion in response to potassium or carbachol was modulated by varying extracellular calcium or by adding halothane or methoxyflurane to the incubation medium, the amount of catecholamine secretion for a given Ca2+ entry was the same.
The action of methoxyflurane on the relationship between intracellular free Ca and exocytosis was examined using electropermeabilised cells, which were suspended in solutions containing a range of concentrations of ionised calcium between 10−8 and 10−4 M. The anaesthetic had no effect on the activation of exocytosis by intracellular free calcium.
Halothane and methoxyflurane inhibited the carbachol‐induced secretion of catecholamines in a non‐competitive manner.
Halothane and methoxyflurane inhibited the increase in22 Na influx evoked by carbachol. For halothane and methoxyflurane this inhibition of Na influx appears to be sufficient to account for the inhibition of the evoked catecholamine secretion.
We conclude that the volatile anaesthetics ethrane, halothane, isoflurane and methoxyflurane inhibit the secretion of adrenaline and noradrenaline induced by carbachol at concentrations that lie within the range encountered during general anaesthesia. In addition all four also inhibit the secretion of catecholamines induced by depolarization with 77 mM K+ but at much higher concentrations. The decrease in Ca influx caused by methoxyflurane accounts fully for the decrease in secretion in response to depolarization with potassium. Similar actions at synapses within the CNS may underlie the general anaesthetic effects of these agents.
Autoradiographic localization and function of β‐adrenoceptors on the human internal mammary artery and saphenous vein
Authors: Molenaar P. , Malta E. , Jones C.R. , Buxton B.F. , Summers R.J. 
Published: July 2012

Receptor autoradiography with (−)‐[125 I]‐cyanopindolol (CYP) was used to study the distribution of β1 and β2‐adrenoceptor subtypes in the human internal mammary artery and saphenous vein.
Images from X‐ray film and nuclear emulsion coated coverslips, exposed to [125 I]‐CYP labelled sections, showed a high density of β2‐adrenoceptors localized to the endothelium of the internal mammary artery and fewer β2‐adrenoceptors on the smooth muscle.
The function of β‐adrenoceptors in ring preparations of the internal mammary artery was investigated in organ bath studies. (−)‐Isoprenaline produced concentration‐dependent relaxation of phenylephrine contracted rings. The potency and maximal effects of (−)‐isoprenaline were not influenced by the presence of the endothelium.
Images of [125 I]‐CYP binding to the saphenous vein, from X‐ray film and nuclear emulsion coated coverslips, showed localization of β2‐adrenoceptors to the outer smooth muscle and not to the endothelium.
Relaxation of mammary artery and saphenous vein to (−)‐isoprenaline is mediated via β2‐adrenoceptors located on the smooth muscle. Endothelial β2‐adrenoceptors, although present on the internal mammary artery, mediate other functions.
Pre‐ and post‐junctional actions of procaterol, a β2‐adrenoceptor stimulant, on dog tracheal tissue
Authors: Ito Yushi 
Published: July 2012

The effects of procaterol, a β2‐adrenoceptor agonist, on excitatory neuro‐effector transmission in the dog trachea were investigated and the findings were compared to those seen with isoprenaline, with microelectrode, double sucrose gap and tension recording methods.
Procaterol (10−10‐ 10‐9 M) and isoprenaline (10−9 M) had no effect on the resting membrane potential or on the input resistance of the smooth muscle cells of dog trachea. However with increased concentrations (>10−8 M), these agents hyperpolarized the membrane and decreased the input resistance of the membrane.
Procaterol (10−10‐10−7 M) and isoprenaline (10−9‐10−7 M) dose‐dependently reduced the amplitude of the twitch contractions evoked by field stimulation in the combined presence of indomethacin (10−5 M) and guanethidine (10−6 m). In parallel with actions on twitch contractions, procaterol (10−10‐10−7 m) and isoprenaline (10−9‐10−7 M) reduced the amplitude of the excitatory junction potentials (e.j.ps), evoked by single pulse field stimulation in the dog trachea.
Procaterol (10−8 M) had no effect on the post‐junctional response of smooth muscle cells to exogenous acetylcholine (ACh) (10−7‐10−6 M).
Pretreatment with ICI‐118551, aβ2‐adrenoceptor blocking agent, reduced the inhibitory action of procaterol on the amplitude of twitch contractions evoked by field stimulations in the dog trachea.
These results indicate that procaterol in low concentrations has a prejunctional action inhibiting the excitatory neuro‐effector transmission in addition to a postsynaptic action, presumably by suppressing transmitter release from the vagus nerve terminals through β2‐adrenoceptors in the dog tracheal tissue. The pre‐ and post‐junctional actions of procaterol explain its potent bronchodilator effects in clinical use.
Antigen‐induced contraction of guinea‐pig isolated trachea: studies with novel inhibitors and antagonists of arachidonic acid metabolites
Authors: Jones T.R. , Charette L. , Denis D. 
Published: July 2012

Responses of antigen‐challenged isolated trachea from sensitized guinea‐pigs were pharmacologically characterized by use of some novel inhibitors and antagonists of arachidonic acid metabolites.
The cyclo‐oxygenase inhibitor, indomethacin, prolonged without altering the maximum response to antigen in the absence of the anti‐muscarinic agent, atropine, and/or the H1receptor blocker, mepyramine. In the presence of mepyramine, indomethacin both prolonged and increased the magnitude of the response. The selective (SQ‐29548) and non‐selective (L‐640, 035) thromboxane A2 (TXA2) antagonist and the TXA2 synthetase inhibitor, OKY‐046, were essentially inactive.
Two novel inhibitors of 5‐lipoxygenase product formation, AA‐861 and L‐651,896 produced complete inhibition of the response to antigen on tissues treated with atropine and mepyramine, with or without indomethacin.
Equimolar concentrations of the leukotriene D4 (LTD4) receptor antagonists LY‐171883 > L‐649,923 ≧ L‐648,051 ≧ FPL‐55712 blocked part of the response to antigen on tissues treated with atropine, mepyramine and indomethacin. All compounds tended to block a larger component of the response in the absence of indomethacin. A similar tendency was observed with the potent phosphodiesterase inhibitor, isobutylmethylxanthine (IBMX) but not the less potent phosphodiesterase inhibitor theophylline.
These results are consistent with the hypothesis that 5‐lipoxygenase products acting on LTD4 receptors play only a minor role in the mediation of the contraction of guinea‐pig trachea to antigen challenge. The nature of the residual contractile mediator is unknown; however, it can be completely blocked by the 5‐lipoxygenase inhibitors AA‐861 and L‐651,896 and non‐selectively blocked by the phosphodiesterase inhibitor, IBMX and non‐selective LTD4 receptor antagonists, such as LY‐171883.
Primary sensory neurones and naloxone‐precipitated morphine withdrawal
Authors: Donnerer Josef 
Published: July 2012

The C‐fibre‐evoked depressor reflex following i.a. injection of capsaicin and the wiping movements following chemical irritation of the cornea by capsaicin were both found to be augmented in the naloxone‐precipitated morphine withdrawal phase.
The in vitro capsaicin‐evoked release of substance P from central terminals of C‐fibre afferents in the spinal cord was decreased in morphine‐treated rats. Following naloxone, the release in the morphine‐treated group was as large as in the control group.
The C‐fibre mediated plasma extravasation in the rat paw after naloxone was found to be the same in morphine‐treated and control rats.
It is concluded that C‐fibre‐evoked reflex reactions are augmented during morphine withdrawal, but that the mechanisms responsible are either located postsynaptically to the primary sensory neurone or further centrally.
Reversal of the cardiotonic and action‐potential prolonging effects of DPI 201–106 by BDF 8784, a methyl‐indol derivative
Authors: Armah Benjamin I. , Pfeifer Thomas , Ravens Ursula 
Published: July 2012

We studied the interaction of the cardiotonic compound DPI 201–106 (4‐[3′‐(4″‐benzhydryl‐1′‐piperazinyl)−2′‐hydroxypropoxy]‐1H‐indole‐2‐carbonitrile; DPI) and its derivative BDF 8784 (2‐methyl‐4‐[3′‐(4″‐benzhydryl‐1”‐piperazinyl)−2′‐hydroxypropoxy]‐1H‐indole; BDF) in isolated right ventricular papillary muscles of guinea‐pig heart.
In contrast to the cardiotonic DPI, the methyl‐indole derivative lacked a positive inotropic effect and even caused negative inotropic effects in concentrations above 1 μm. At 10 μm BDF significantly reduced the force of contraction and dV/dtmax' but did not affect action potential duration (APD).
Pretreatment of papillary muscles with BDF prevented the positive inotropic action of DPI in a concentration‐dependent, but non‐competitive fashion. At 10 μm, BDF prevented the inotropic effect of racemic DPI and shortened the DPI‐induced prolongation of action potential duration. BDF similarly affected the inotropic and APD‐prolonging effects of the sea anemone polypeptide ATX II.
In cardiac myocytes, DPI induced a tetrodotoxin (TTX)‐sensitive, slowly inactivating inward current. The slow decay of this current was enhanced by BDF. In cells pretreated with BDF, DPI was not effective. BDF alone depressed the sodium and the calcium current.
In conclusion, the non‐inotropic methyl‐indole derivative BDF interacts with DPI non‐competitively at the sodium channels to abolish the inotropic and APD‐prolonging effects of DPI, emphasizing the importance of the substituent in position 2 of the indole moiety for this effect.
The relaxant properties of human calcitonin gene‐related peptide on vascular and extravascular (capsular) smooth muscle of the isolated blood‐perfused spleen of the anaesthetized dog
Authors: Withrington P.G. 
Published: July 2012

The 37 amino acid human calcitonin gene‐related peptide (CGRP), was injected intra‐arterially into the isolated, blood perfused spleen of the dog.
The only vascular response observed to CGRP, once threshold had been reached (10–20 fmol), was a dose‐dependent splenic arterial vasodilatation.
The mean intra‐arterial bolus dose of CGRP to reduce the splenic arterial vascular resistance by 50% of maximum response was 0.52 ± 0.12 pmol. This value was significantly lower than the ED50 for the non‐selective β‐adrenoceptor agonist isoprenaline (P < 0.01) in the same experiments. CGRP is the most potent splenic vasodilator yet tested.
The mean maximum vasodilator response to CGRP was significantly less (P < 0.01) than that achieved with isoprenaline.
The time course of the splenic arterial vascular response to CGRP was substantially longer than that to isoprenaline.
The splenic vasodilator response to CGRP was not altered by the prior administration of the selective β2‐adrenoceptor antagonist, ICI 118,551.
At all doses of CGRP that caused splenic vasodilatation there were substantial increases in spleen volume. The time course of the response and slope of the regression line suggested an active capsular relaxation component.
In view of its location within the spleen and high molar potency, CGRP may be considered as a potential factor in the local control of the circulation through the spleen.
8‐OH‐DPAT, flesinoxan and guanfacine: systemic and regional haemodynamic effects of centrally acting antihypertensive agents in anaesthetized rabbits
Authors: Hof R.P. , Fozard J.R. 
Published: July 2012

8‐Hydroxy‐2‐(di‐n‐propylamino) tetralin (8‐OH‐DPAT) and flesinoxan, agents which show high affinity and selectivity for 5‐HT1A receptors, were administered intravenously in doses of 0.003 to 0.1 and 0.01 to 0.3 mg kg−1 respectively to 5 rabbits each. Their effects were compared with those of the centrally acting agent and α2‐adrenoceptor agonist, guanfacine, 0.01–0.3 mg kg−1, administered to a group of 5 rabbits. Five further rabbits were used as controls and treated with the vehicle of the active agents.
Both flesinoxan and 8‐OH‐DPAT induced similar systemic and regional haemodynamic changes. Both lowered mean arterial pressure and heart rate. The principal blood pressure lowering mechanism was vasodilatation; cardiac output changed minimally despite the falls in heart rate and myocardial contractile force.
With guanfacine the maximal fall of blood pressure was comparable to that obtained with the 5‐HT1A receptor ligands; however, in contrast to the latter, the dose‐response curve was U‐shaped, the highest dose eliciting a pressor effect with reversal of the vasodilatation.
Widespread peripheral vasodilatation was found with all the agents in the splanchnic circulation and also in the brain and skeletal muscle. A weak tendency towards vasodilatation was found in the kidneys where the dose‐response curve was bell‐shaped for guanfacine.
This spectrum of activity is different from that of peripheral vasodilators, such as calcium antagonists, potassium channel activating agents or hydralazine; it is, however, consistent with the putative mechanism of action of these compounds to reduce peripheral sympathetic tone by a central mechanism of action.
Differential antagonism of the negative inotropic effect of gentamicin by calcium ions, Bay K 8644 and isoprenaline in canine ventricular muscle: comparison with cobalt ions
Authors: Hashimoto Hiroo , Yanagisawa Teruyuki , Taira Norio 
Published: July 2012

Gentamicin (10−4−10−2 m) and Co2+ (10−4 — 10−2 m) produced a decrease in developed tension of canine isolated ventricular muscles leading to near abolition at 10−2m. Their negative inotropic effects developed rapidly and wore off shortly after wash‐out.
The concentration‐negative inotropic effect curves for gentamicin were shifted to the right in a parallel manner by increasing external Ca2+, or by the presence of Bay K 8644 (10−7−10−5m) or isoprenaline (10−7−10−5m). IC50 values for gentamicin increased about 3‐fold with about a 6 fold increase in external Ca2+. The Schild plot yielded a pA2 of 2.29 for Ca2+ and its slope was −1.17 (r = −0.79).
The concentration‐negative inotropic effect curves for Co2+ were shifted to the right in a parallel manner by increasing external Ca2+, or by the presence of isoprenaline (10−7−10−5m). IC50 values for Co2+ increased about 5 fold with about a 6 fold increase in external Ca2+. The Schild plot gave a pA2 value of 2.60 for Ca2+ and its slope was −1.11 (r = −0.86).
The concentration‐positive inotropic effect curves for Ca2+, which were computer‐fitted to a logistic equation, gave 2.88 × 10−3 m for EC50. This value was very close to the KCa calculated from pA2 values for Ca2+ based on antagonism between gentamicin or Co2+ and Ca2+ (5.13 × 10−3 and 2.51 × 10−3 m).
It is concluded that like Co2+, gentamicin molecules compete with Ca2+ for the same binding sites presumably located at the outer orifice of Ca‐channels in the cardiac sarcolemma.