bluuebunny/crossref_metadata_2025_split huggingface dataset:
5‐Carboxamidotryptamine is a selective agonist at 5‐hydroxytryptamine receptors mediating vasodilatation and tachycardia in anaesthetized cats
Authors: Connor H.E. , Feniuk W. , Humphrey P.P.A. , Perren M.J. 
Published: July 2012

We have attempted to characterize the 5‐hydroxytryptamine (5‐HT) receptors mediating bronchoconstriction, vasodilatation, vasodepression and tachycardia in anaesthetized cats following bilateral vagosympathectomy and β‐adrenoceptor blockade with propranolol.
5‐HT (1–100 μg kg−1 i.v.) caused dose‐related bronchoconstriction and tachycardia but variable and complex effects on diastolic blood pressure and carotid arterial vascular resistance.
In contrast, 5‐carboxamidotryptamine (5‐CT; 0.01–1 μg kg−1 i.v.) caused consistent, dose‐related decreases in diastolic blood pressure and carotid arterial vascular resistance and increases in heart rate. 5‐CT did not cause bronchoconstriction.
The 5‐HT‐induced bronchoconstriction was dose‐dependently antagonized by methiothepin, methysergide and ketanserin (10–100 μg kg−1 i.v.). The highest doses used of these antagonists did not antagonize bronchoconstriction induced by prostaglandin F2α. The high potency of all three antagonists indicate a 5‐HT2‐receptor mediated effect.
The 5‐HT‐ and 5‐CT‐induced tachycardia as well as the 5‐CT‐induced vasodepressor and carotid arterial vasodilator responses were dose‐dependently antagonized by low doses of methiothepin (10–100 μg kg−1 i.v.) and by high doses of methysergide (100–1000 μg kg−1 i.v.) but were little affected by ketanserin in doses up to 1000 μg kg−1 i.v. These selective effects of 5‐CT appear to be mediated by ‘5‐HT1‐like’ receptors.
Modulation of in vitro anaphylaxis of guinea‐pig isolated tracheal segments by azelastine, inhibitors of arachidonic acid metabolism and selected antiallergic drugs
Authors: Chand N. , Diamantis W. , Sofia R.D. 
Published: July 2012

The ability of azelastine to influence antigen‐induced contractile responses (Schultz‐Dale phenomenon) in isolated tracheal segments of the guinea‐pig was investigated and compared with selected antiallergic drugs and inhibitors of arachidonic acid metabolism.
Indomethacin produced a significant leftward shift of the antigen concentration‐effect curve.
The inhibitory activity of azelastine on anaphylactic responses in guinea‐pig trachea was dependent on the duration of exposure (preincubation period).
The relative order of potency (antianaphylactic activity) at calculated IC50 level was as follows: FPL 55712 (a leukotriene receptor antagonist) > nordihydroguaiaretic acid (a lipoxygenase inhibitor) > p‐bromophenacyl bromide (a phospholipase A2 inhibitor) > BW 755c (a dual inhibitor of lipoxygenase and cyclo‐oxygenase) > theophylline (a phosphodiesterase inhibitor) > azelastine > diphenhydramine (H1 histamine‐receptor antagonist) > ketotifen > disodium cromoglycate. FPL 55712 (added 5 min before antigen challenge) was about 12 times as potent as azelastine (added 2 h before antigen challenge).
The incubation of tracheal segments with azelastine and BW 755c for a period of 30 min was found to inhibit indomethacin‐augmented anaphylactic responses. These observations seem to suggest that azelastine and BW 755c interfere with the synthesis/release of the products of lipoxygenase/leukotriene synthetase pathway (e.g., leukotrienes) in the mediation of allergic responses in airway smooth muscles.
Postsynaptic α1‐ and α2‐adrenoceptors in the vascular system of the herring gull, Larus argentatus
Authors: Hermansson Lars‐Erik , Johansson Pehr 
Published: July 2012

The nature of the vascular α‐adrenoceptors has been studied in the herring gull, Larus argentatus.
In the anaesthetized herring gull, both phenylephrine and clonidine elicited dose‐dependent increases in arterial blood pressure.
The α1‐adrenoceptor antagonist prazosin was a better antagonist of phenylephrine than were the α2‐adrenoceptor antagonists yohimbine and rauwolscine.
Yohimbine and rauwolscine were better antagonists of clonidine than was prazosin.
The maximum response to phenylephrine, but not clonidine, was lower in reserpine‐treated birds, indicating that phenylephrine in high doses liberates endogenous catecholamines, which contribute to the effect.
It is concluded that the herring gull possesses postsynaptic, vascular α‐adrenoceptors, of both the α1‐ and α2‐subtypes, similar to those found in mammals.
In vitro effects of calcium entry blockers, chlorpromazine and fenoterol upon human pregnant myometrium contractility
Authors: Ballejo Gustavo , Calixto João B. , Medeiros Yara S. 
Published: July 2012

The inhibitory effects of nifedipine, verapamil, cinnarizine (calcium entry blockers), chlorpromazine (a putative calmodulin antagonist) and fenoterol (a β2‐adrenoceptor agonist) on contractility in human isolated pregnant myometrium were studied.
Spontaneous contractions (present in 93% of the preparations) were inhibited in a concentration‐related manner by these compounds in the following order of potency: nifedipine > verapamil >> cinnarizine > chlorpromazine. Cinnarizine was effective only at a concentration greater than 100 μM. Fenoterol, at 10 μM, did not produce an inhibitory effect but decreased the frequency of spontaneous contractions.
All drugs, except fenoterol, produced a concentration‐dependent relaxation of K+‐induced contractions in the following order of sensitivity: nifedipine > verapamil >> chlorpromazine. Cinnarizine produced only about 40% of relaxation. Under these conditions nifedipine and verapamil were about 80 and 5 fold more potent respectively than when tested against spontaneous contractions. The potencies of chlorpromazine and cinnarizine did not differ in the two experimental conditions.
Both the spontaneous and K+‐induced contractions were inhibited in a time‐dependent manner in Ca2+‐free media and the responses were almost completely abolished in 70–100 min. Calcium addition to the medium rapidly restored both spontaneous or K+‐induced contractions.
To investigate further the role of intracellular calcium, K+‐depolarized preparations contracted by calcium 3 mM (40–60% of maximal contractions) were relaxed by these compounds. Nifedipine and verapamil showed a relaxation time course similar to that induced by calcium removal. Cinnarizine and fenoterol had no relaxant effect while chlorpromazine induced a slight and slow relaxation.
These findings suggest that calcium influx and calmodulin are involved in spontaneous contractions of pregnant human myometrium in vitro. Since nifedipine and verapamil were more potent against K+‐induced than spontaneous contractions, calcium channels activated by these conditions could be different. Finally, fenoterol, a β2‐adrenoceptor agonist, widely used as a tocolytic agent, blocked neither spontaneous nor K+‐induced contractions.
The mechanisms by which haemoglobin inhibits the relaxation of rabbit aorta induced by nitrovasodilators, nitric oxide, or bovine retractor penis inhibitory factor
Authors: Martin William , Smith Jerry A. , White David G. 
Published: July 2012

The mechanisms by which haemoglobin and methaemoglobin inhibit the vasodilator actions of glyceryl trinitrate, sodium azide, nitric oxide, and the bovine retractor penis inhibitory factor (IF) were studied on rabbit endothelium‐denuded aortic rings.
Methaemoglobin was less effective than haemoglobin against each vasodilator, it was more effective at inhibiting the relaxation to azide than that to glyceryl trinitrate.
Glyceryl trinitrate was neither bound nor inactivated when passed through columns of haemoglobin‐agarose or methaemoglobin‐agarose. Azide was reversibly bound but less by haemoglobin‐agarose than by methaemoglobin‐agarose. Inhibition of the vasodilator actions of glyceryl trinitrate is not attributable therefore to a direct interaction with the haemoproteins, although a small part of the inhibition of azide‐induced relaxation by methaemoglobin is likely to be due to a direct interaction.
Columns of haemoglobin‐agarose were more effective than columns of methaemoglobin‐agarose in removing nitric oxide from solution. The greater ability of haemoglobin, compared to methaemoglobin, to inhibit vasodilatation induced by nitrovasodilators may therefore reflect the greater ability of haemoglobin to bind nitric oxide which is the active principle of the nitrovasodilators.
Neither the acid‐activated nor the inactive forms of IF were bound or inactivated when passed through columns of methaemoglobin‐agarose. Neither form of IF was retained on passage through colomns of haemoglobin‐agarose, but the resulting activity in the eluates was less than control, was unstable and, unlike the original activity, decayed rapidly on ice. The greater ability of haemoglobin, compared to methaemoglobin, to inhibit vasodilatation induced by IF might therefore reflect the greater ability of haemoglobin to interact with this vasodilator and inactivate it.
D2‐dopamine receptor‐mediated inhibition of intracellular Ca2+ mobilization and release of acetylcholine from guinea‐pig neostriatal slices
Authors: Fujiwara Hiroshi , Kato Noriko , Shuntoh Hisato , Tanaka Chikako 
Published: July 2012

The effect of dopamine receptor activation on electrically‐or high K+ (30 mm)‐evoked neurotransmitter release and rise in intracellular Ca2+ concentration was investigated using slices of guinea‐pig neostriatum.
A specific D2‐dopamine receptor agonist, LY‐171555 (a laevorotatory enantiomer of LY‐141865: N‐propyl tricyclic pyrazole) at 10−6 m inhibited electrical stimulation‐and high K+‐evoked release of [3H]‐acetylcholine ([3H]‐ACh) to 47.7 ± 6.0% and 54.1 ± 5.0% of control, respectively. The maximal inhibition by LY‐171555 at 10−5 m was 54.8 ± 5.1% reduction of the control. The half‐maximal effective concentration (EC50) of LY‐171555 for the inhibition of [3H]‐ACh release was 2.3 × 10−7 m. A specific D2‐dopamine receptor antagonist, (−)‐sulpiride (10−7 m) reversed the inhibition of [3H]‐ACh release induced by LY‐171555. A specific D1‐dopamine receptor agonist, SK&F 38393 (2,3,4,5‐tetrahydro‐7,8‐dihydroxy‐1‐phenyl‐1H‐benzazepine) (10−5 m) had no effect on the release of [3H]‐ACh. LY‐171555 (10−6 m) also inhibited the high K+‐evoked endogenous glutamate release, by 47% of control. This inhibitory effect was reversed by (−)‐sulpiride (10−7 m).
We used a fluorescent, highly selective Ca2+ indicator, ‘quin 2’ to measure intracellular free Ca2+ concentrations ([Ca2+]i). Electrical stimulation of slices preloaded with quin 2 led to an elevation of relative fluorescence intensity and this response was reduced by the removal of Ca2+ from the bathing medium. These results indicate that the enhanced elevation in fluorescence intensity in the quin 2‐loaded slices reflects the increase of intracellular free Ca2+ concentration, [Ca2+]i.
The mixed D1‐and D2‐receptor agonist, apomorphine and LY‐171555 inhibited the increase of [Ca2+]i induced by electrical stimulation or high K+ medium, in a concentration‐dependent manner, while SK&F 38393 did not affect the increase of [Ca2+]i. The maximal inhibitory effect of LY‐171555 at 3 × 10−5 m was 35 ± 3% reduction in control values. The inhibitory effect of LY‐171555 was antagonized by (−)‐sulpiride (10−7 m).
There was a high correlation (r = 0.997, P < 0.05) between the D2‐receptor‐mediated inhibition of the stimulated rise of [Ca2+]i and [3H]‐ACh release.
When the slices were superfused with the Ca2+‐free medium containing EGTA (10−4 m) for 5 min, the rise in [Ca2+]i was markedly suppressed to 18.0% of control by LY‐171555 (10−6 m).
These data indicate that activation of the D2‐dopamine receptor suppresses the elevation of [Ca2+]i induced by depolarizing stimuli. This may be due to inhibition of mobilization of Ca2+ from the intracellullar store. We propose that the D2‐receptor‐mediated inhibition of transmitter release is probably due to a reduction in intracellular Ca2+ mobilization.
Electrophysiological effects of Ca antagonists, tetrodotoxin, [Ca]o and [Na]o on myocardium of hibernating chipmunks: possible involvement of Na‐Ca exchange mechanism
Authors: Kondo Noriaki 
Published: July 2012

The electrophysiological performance of myocardium of hibernating chipmunks was investigated in the presence of Ca antagonists and tetrodotoxin, and the effects of high [Ca]o and low [Na]o were examined.
The action potential of the preparations was characterized by the low amplitude of the plateau phase (APp). Ca antagonists, nifedipine (10−6 m) and nitrendipine (2 × 10−6 m), did not significantly inhibit this APp or the contraction.
These nifedipine‐insensitive electromechanical responses were completely abolished by an internal Ca release inhibitor, ryanodine.
Both increasing [Ca]o and lowering [Na]o, by replacing Na by lithium or choline, also inhibited APp.
Tetrodotoxin (10−5 m) which markedly inhibited the initial rapid phase of the action potential slightly affected APp.
These results suggest that the plateau potential of the present preparations is controlled by a process linked to Ca release from internal stores, most likely the Na‐Ca exchange mechanism.
pH‐dependent stimulation by Ca2+ of prostacyclin synthesis in rat aortic rings: effects of drugs and inorganic ions
Authors: Ritter J.M. , Frazer C.E. , Taylor G.W. 
Published: July 2012

Fresh rat aortic rings were incubated in HEPES‐buffered salt solutions. Extracellular Ca2+ stimulated the production of prostacyclin (PGI2), as determined by radioimmunoassay of its stable hydrolysis product 6‐oxo‐prostaglandin F1α. This action of Ca2+ was modified by H+ over the pH range 8.0–6.5. Stimulation by calcium ionophore A23187 was not pH‐dependent.
In parallel incubations of aortic rings with 45 Ca2+, followed by washing in the presence of La3+, tissue uptake of 45Ca2+ increased progressively as extracellular pH was increased from 6.5–8.0. Over this range intracellular pH, estimated by the distribution of [14C]‐dimethadione, varied from 5.9‐7.4.
Stimulation by Ca2+ of PGI2 synthesis was concentration‐dependent over the range 0.7–20 mm. The maximum effect was an increase of approx. 4 fold.
Nifedipine, but not verapamil or diltiazem, inhibited Ca2+‐stimulated PGI2 synthesis. A dihydropyridine compound that activates voltage‐dependent Ca2+ channels, Bay K 8644, did not increase PGI2 synthesis.
8‐(N, N‐diethylamino)‐octyl‐3,4,5 timethoxybenzoate (TMB‐8), an antagonist of intracellular Ca2+ mobilisation, inhibited basal and Ca2+‐stimulated PGI2 synthesis to a similar extent.
A solution containing 40 mm K+ reduced Ca2+‐stimulated PGI2 production. Mg2+ stimulated PGI2 synthesis in a pH‐dependent manner but was less potent than Ca2+. Other divalent cations (Mn2+, Ba2+ and Sr2+), and La3+ had little or no effect on basal or Ca2+‐stimulated PGI2 synthesis.
Effect of gastric secretagogues on the formation of inositol phosphates in isolated gastric cells of the rat
Authors: Puurunen Juhani , Schwabe Ulrich 
Published: July 2012

The effects of compounds affecting gastric acid secretion were studied on the formation of inositol phosphates after prelabelling with [3H]‐inositol in enriched gastric parietal cells of the rat, prepared by isopycnic centrifugation with Percoll.
In cell preparations with 60 to 70% parietal cells, carbachol (10−6‐10−2 m) enhanced the accumulation of [3H]‐inositol monophosphate ([3H]‐IP1), [3H]‐inositol bisphosphate ([3H]‐IP2) and [3H]‐inositol trisphosphate ([3H]‐IP3) in a concentration‐dependent manner, an effect which was antagonized by 10−8 m atropine.
Li+ (0.5 − 30 mm) enhanced the basal and carbachol‐induced accumulation of all three [3H]‐inositol phosphates, the formation of [3H]‐IP1 being more sensitive to Li+ than those of [3H]‐IP2 and [3H]‐IP3.
The concentration of Ca2+ in the incubation medium did not affect the relative stimulation of the accumulation of [3H]‐inositol phosphates by carbachol, although the basal formation was higher in the presence of Ca2+ in the medium. In the absence of added Ca2+, the incorporation of [3H]‐inositol into phospholipids was increased—an effect which was further enhanced by the addition of EGTA to the medium.
Gastrin and pentagastrin (10−8 −10−5 m) enhanced the formation of [3H]‐inositol phosphates, although they were clearly less effective than carbachol. Histamine (10−6−10−3 m) had no effect of its own, but slightly attenuated the effect of carbachol. Cholecystokinin octapeptide (10−9−10−6 m) slightly increased the formation of [3H]‐inositol phosphates.
Indomethacin (10−4 m) had no consistent effect on the basal and carbachol‐induced accumulation of [3H]‐inositol phosphates, nor did prostaglandin E2 (10−5 m) modify it.
Adrenaline (10−3 m), 5‐hydroxytryptamine (10−3 m), forskolin (10−5 m), vasopressin (10−5 m), angiotensin II (10−5 m) and bombesin (10−9‐10−6 m) were all without effect.
We suggest that the hydrolysis of inositol phospholipids may be involved in the signal transduction mechanism by which the activation of the muscarinic and gastrin receptors on the parietal cells leads to Ca2+ mobilization and the stimulation of hydrogen ion secretion.
Effects of 5‐hydroxy‐propafenone in guinea‐pig atrial fibres
Authors: Delgado C. , Tamargo J. , Tejerina T. , Valenzuela C. 
Published: July 2012

The effects of 5‐hydroxy‐propafenone (5‐OH‐P), an active metabolite of propafenone, were studied on isolated atrial muscle fibres obtained from non‐treated guinea‐pigs and from animals pretreated with 5‐OH‐P, 3 mg kg−1, for 28 days.
In untreated atria 5‐OH‐P, 10−8 m‐10−4 m, produced a dose‐dependent decrease in amplitude and df/dtmax and reduced the amplitude of the slow contractions induced by isoprenaline and histamine in high K+ media.
5‐OH‐P also produced a dose‐dependent decrease in atrial rate, prolonged the sinus node recovery time and reduced the maximum chronotropic responses to isoprenaline.
In untreated atrial muscle fibres 5‐OH‐P depressed action potential amplitude and Vmax, reduced the resting membrane potential and prolonged the action potential duration (ADP) and the effective refractory period, lengthening the effective refractory period relative to APD.
Pretreatment with 5‐OH‐P reduced atrial rate and increased contractile force, but did not modify the action potential characteristics from the values obtained in untreated atria. Further addition of 5‐OH‐P produced similar but more marked changes than in untreated atria.
It is concluded that in guinea‐pig isolated atrial muscle fibres 5‐OH‐P, like propafenone, exhibits class I (membrane stabilizing), class II (antisympathetic) and class IV (Ca antagonistic) antiarrhythmic actions. Therefore, this metabolite could be responsible, at least in part, for some of the antiarrhythmic effects previously attributed to propafenone.
Cellular electrophysiological effects of d‐and dl‐sotalol in guinea‐pig sinoatrial node, atrium and ventricle and human atrium: differential tissue sensitivity
Authors: Campbell Terence J. 
Published: July 2012

The effects of racemic dl‐sotalol and d‐sotalol on guinea‐pig sino‐atrial node, atrium and ventricle and on human atrium were studied using standard microelectrode techniques. Both compounds increased spontaneous sinus node cycle length largely by prolonging the repolarization phase of the action potentials. This effect was attributed to blockade of outward potassium current.
Ventricular action potential duration was similarly prolonged by dl‐sotalol at concentrations of 5–50 μm.
dl‐Sotalol 1–50 μm had no effect on guinea‐pig atrial action potential duration and d‐sotalol produced minor prolongation only at the highest concentration (50 μm).
Human atrial action potentials were, however, significantly prolonged by both dl‐AND d‐sotalol 10 μm. This indicates differential sensitivities to sotalol for human and guinea‐pig atrium and explains the ability of sotalol to prolong atrial monophasic action potential duration in clinical studies.
The role of blood vessels in the bioconversion of leukotrienes in the pig
Authors: Galton Simon A. , Piper Priscilla J. 
Published: July 2012

Porcine pulmonary artery has the ability to convert leukotriene C4 (LTC4) to LTD4 and then to LTE4.
In this vessel, there appears to be no further metabolism beyond LTE4.
LTC4 (1 nm) is converted rapidly to LTD4, whereas the conversion of LTD4 to LTE4 is somewhat slower.
The conversion of LTC4 to LTD4 is inhibited by the γ‐glutamyl transpeptidase inhibitor, serine‐borate (45 mm).
The conversion of LTD4 to LTE4 is inhibited by the aminopeptidase inhibitor, l‐cysteine (10 mm).
LTB4 did not appear to be metabolized by porcine pulmonary artery.
These results suggest that the vessel wall may play a role in the early stages of leukotriene metabolism.
Effect of neomycin on post‐tetanic twitch tension of the mouse diaphragm preparation
Authors: Tsai M.C. 
Published: July 2012

The effect of calcium (0.5–6 mm) and neomycin (0.1‐0.2 mm) on the maximum post‐tetanic twitch tension (MTT) and post‐tetanic depression (PTD) of the indirectly elicited twitch tension was studied on the mouse isolated phrenic nerve‐diaphragm preparation. The effect of neomycin on MTT of directly stimulated twitch tension was also tested in (+)‐tubocurarine pretreated preparations.
Three‐dimensional plots between MTT and frequency and duration of indirect tetanic stimulation revealed that the frequencies and durations inducing maximal MTT were 500 Hz for 20 s in 0.5 mm CaCl2, 100 Hz for 5 s in 2 mm CaCl2 and 100 Hz for 10 s in 6 mm CaCl2. The frequency and duration inducing maximal PTD was 100 Hz for 20 s in 0.5 mm CaCl2, but there was no PTD in 2 mm or 6 mm CaCl2.
Neomycin was associated with significantly greater MTT than in control if the duration of tetanic stimulation was 1 or 2 s, while it was associated with less MTT if the duration of tetanic stimulation was 10 or 20 s.
Neomycin caused PTD in 2 mm CaCl2; sometimes the depressive effect was so severe that twitch tension was abolished. The maximal depression effect was found after 100 Hz tetanic stimulation for 20 s. Increasing the extracellular calcium concentration to 6 mm antagonized the effects of neomycin on MTT and PTD, whereas neostigmine (1.6 μm) antagonized the effect partially.
Neomycin had no effect on the MTT or PTD of the directly stimulated twitch tension.
It is concluded that neomycin alters the conditions of tetanic stimulation inducing MTT.
Glutamate‐evoked release of endogenous brain dopamine: inhibition by an excitatory amino acid antagonist and an enkephalin analogue
Authors: Jhamandas Khem , Marien Marc 
Published: July 2012

The present study examined the effect of a selective δ‐opioid receptor agonist [d‐Ala2‐d‐Leu5] enkephalin (DADL) on the spontaneous and the l‐glutamic acid (l‐Glu)‐evoked release of endogenous dopamine from superfused slices of rat caudate‐putamen. The amount of dopamine in slice superfusates was measured by a sensitive method employing high‐performance liquid chromatography with electrochemical detection (h.p.l.c.‐e.d.) after a two‐step separation procedure.
The spontaneous release of endogenous dopamine was (a) partially dependent on Ca2+, (b) enhanced in Mg2+‐free superfusion medium, (c) partially reduced by tetrodotoxin (TTX, 0.3 μm), (d) partially reduced by the putative excitatory amino acid receptor antagonist dl‐2‐amino‐7‐phosphonoheptanoic acid (dl‐APH, 1 mm), and (f) increased 10 fold by the dopamine uptake blocker, nomifensine (10 μm). DADL (5 and 50 nm) did not significantly affect spontaneous dopamine release.
l‐Glu (0.1–10 mm) produced a concentration‐dependent release of endogenous dopamine from slices of caudate‐putamen. This effect was (a) Ca2+‐dependent, (b) strongly inhibited by 1.2 mm Mg2+, (c) attenuated by dl‐APH (1 mm), (d) attenuated by TTX (0.3 μm), and (c) enhanced by nomifensine (10 μm). In the presence of nomifensine DADL (50 nm) reduced significantly the l‐Glu‐evoked release of endogenous dopamine by 20%. The inhibitory effect of DADL was blocked by 10 μm naloxone.
These results indicate tht l‐Glu stimulates the Ca2+‐dependent release of endogenous dopamine in the caudate‐putamen by activation of N‐methy‐d‐aspartate‐type of excitatory amino acid receptors. This release can be selectively modified by the δ‐opioid agonist DADL in a naloxone‐sensitive manner.