bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmaco‐mechanical coupling in the response to acetylcholine and substance P in the smooth muscle of the rat iris sphincter
Authors: Banno Hitoshi , Imaizumi Yuji , Watanabe Minora 
Published: July 2012

In the rat iris sphincter muscle contractile responses to transmural stimulation consisted of two components, a fast cholinergic followed by a slow non‐adrenergic, non‐cholinergic (NANC) one. The magnitude of the latter varied widely and was on average 5% of that of the cholinergic component.
Exogenous substance P (1 nM‐1 μM) produced a concentration‐dependent contraction, the maximum amplitude of which was as large as that produced by acetylcholine (ACh).
Capsaicin (10 μM) induced a transient contraction only once in each preparation. After the treatment with capsaicin the NANC component disappeared.
Neither nerve nor direct electrical stimulation with short pulses elicited any active change in the membrane potential under physiological conditions, but an action potential was triggered by direct stimulation when the extracellular Ca ion was totally replaced by Ba ion. Under the latter conditions spontaneous spike potentials occurred repetitively.
ACh and substance P produced a large contraction without modifying the membrane potential. This was also the case in the presence of 5 mM Ba.
These results suggest that substance P‐ergic innervation may have a far lesser physiological significance than that which has been described in rabbits and that pure pharmaco‐mechanical coupling is characteristic of the responses to acetylcholine, substance P, and nerve stimulation in the rat iris sphincter muscle.
Pharmacological investigation into the effects of histamine and histamine analogues on guinea‐pig and rat colon in vitro
Authors: Aguilar María‐José , Morales‐Olivas Francisco J. , Rubio Elena 
Published: July 2012

The effects of histamine and specific histamine agonists has been examined on isolated longitudinal colon strips of guinea‐pig and rat.
Histamine and 2‐pyridyl‐ethylamine but not 4 methylhistamine produced a concentration‐related contractile response in the guinea‐pig colon.
The H1‐antagonist clemizole antagonized competitively the effect of histamine but the H2‐antagonist ranitidine did not modify the dose‐response curve to histamine in the guinea‐pig colon.
Atropine, hexamethonium, prazosin and propranolol failed to modify the contractile response to histamine.
Tone induced with KCl in guinea‐pig isolated colon was not modified by histamine agonists even in tissues pretreated with clemizole or ranitidine.
Histamine and histamine analogues were without effect on the isolated longitudinal strip of the rat colon.
It is concluded that histamine produced dose‐dependent contractions of the guinea‐pig colon due to direct activation of H1‐histamine receptors. There is no evidence in favour of the existence of H2‐histamine receptors in this preparation. The lack of effect of histamine agonists in rat colon strip argues against the existence of histamine receptors in this preparation.
The antinociceptive action of some β‐adrenoceptor agonists in mice
Authors: Bentley G.A. , Starr Jennifer 
Published: July 2012

The antinociceptive actions of several β‐adrenoceptor agonist drugs have been studied in mice by use of a modified abdominal constriction test.
All the drugs studied had high antinociceptive activity, with ID50 values in the nmol kg−1 range. (−)‐Isoprenaline and (±)‐isoxsuprine were the most potent, being about ten times more active than salbutamol, the least potent drug studied. All these drugs produced their action very rapidly and appear to act within the peritoneum.
(−)‐Isoprenaline had about six times the potency of the (+)‐isomer.
(±)‐Propranolol caused rightward shifts, usually parallel, of the dose‐response curves for (−)‐isoprenaline. (+)‐Propranolol was more than ten times less potent than the racemic drug.
Practolol also caused parallel, rightward shifts of the dose‐response curves for (−)‐isoprenaline, and was about twice as potent as (±)‐propranolol, whether given by subcutaneous or intraperitoneal injection. Atenolol and ICI 118551 had intermediate potencies.
Propranolol, practolol and ICI 118551 were all considerably less potent in antagonizing the antinociceptive actions of fenoterol and RO363, than (−)‐isoprenaline. None of these antagonist drugs showed more than a slight ability to discriminate between the β1‐ and β2‐selective agonist drugs.
No evidence was found for the involvement of opioid, dopamine, or α‐adrenoceptors in the antinociceptive action of the β‐adrenoceptor agonist drugs. Evidence for and against the involvement of β‐adrenoceptors is discussed, and it is concluded that if these receptors do mediate the antinociceptive action they appear to be atypical.
The effects of long‐term infusion of salbutamol, diltiazem and nifedipine on uterine contractions in the ovariectomized, post‐partum rat
Authors: Abel Margaret H. , Hollingsworth M. 
Published: July 2012

The sensitivity of the uterus to the inhibition of contractions by salbutamol, diltiazem or nifedipine was assessed in the ovariectomized, post‐partum rat by dose‐response curves following bolus intravenous (i.v.) administration. These tests were performed before (day 1), immediately after a 20 h i.v. infusion of salbutamol, diltiazem, nifedipine or appropriate control infusate (day 2) and after a further 20 h infusion of saline (day 3). In a further group of animals sensitivity to nifedipine was assessed before and after a 20 h infusion of salbutamol. Uterine contractions were monitored throughout infusions.
Infusion of salbutamol (2 μg kg−1 min−1) produced an initial marked inhibition of uterine contractions, an effect which was not maintained despite continued infusion. Contractions reappeared after 2 h of infusion and reached pre‐infusion levels by 5 h. The dose‐response curve to salbutamol on day 2 was shifted more than 100 fold to the right compared with that on day 1. Sensitivity of the uterus on day 3 did not differ from that on day 1.
Nifedipine (25 μg kg−1 min−1) produced sustained inhibition of uterine contractions throughout the 20 h of infusion. Sensitivity of the uterus to nifedipine could not, therefore, be tested on day 2; sensitivity on day 3 did not differ from that on day 1. In addition, there was no change in sensitivity of the uterus to nifedipine after a 20 h infusion of salbutamol.
Diltiazem (200 μg kg−1 min−1) produced a marked initial inhibition of uterine contractions, with a partial return of contractions during continued infusion in 7 out of 12 animals so that mean integral values reached 40% of those pre‐infusion. The dose‐response curve to diltiazem on day 2 showed a 25 fold shift to the right compared with that on day 1 in 4 out of 12 animals where the test could be performed. Sensitivity of the uterus on day 3 did not differ from that on day 1.
These findings suggest that marked but reversible tolerance to the inhibitory actions of salbutamol on uterine contractions occurs during long‐term infusion. There was no evidence of tolerance to the uterine actions of nifedipine, but there was evidence of tolerance to diltiazem in some animals.1
Coronary vasoconstriction in the rat, isolated perfused heart induced by platelet‐activating factor is mediated by leukotriene C4
Authors: Piper Priscilla J. , Stewart A.G. 
Published: July 2012

Platelet‐activating factor (Paf, 0.04‐4.50 nmol) dose‐dependently induced coronary vasoconstriction and decreased cardiac contractility in rat, isolated perfused hearts and concomitantly released leukotriene‐like bioactivity into the cardiac effluent.
Platelet‐activating factor (0.9 nmol) induced an increase in 6‐keto‐prostaglandin F1α (6‐keto‐PGF1α), PGF2α, PGE2 and thromboxane B2 (TXB2) measured by radioimmunoassay (RIA) of cardiac effluents following partial purification using C18 Sep‐Paks.
The leukotriene‐like bioactivity released by Paf was identified as leukotriene C4 (LTC4) using a combination of isolation on reverse phase‐h.p.l.c. (r.p.h.p.l.c.) and quantitation by RIA. In addition, LTB4 was also identified by r.p.h.p.l.c. and the levels, determined by RIA, were within the range having biological activity.
The release of cyclo‐oxygenase products by Paf was prevented by indomethacin (2.8 μM), markedly attenuated by diethylcarbamazine (7.7 mM) but unaffected by FPL 55712 (1.9 μM)‐pretreatment. Furthermore, LTC4 (50 pmol) did not increase the release of the cyclo‐oxygenase products measured.
The release of LTB4 and LTC4 appeared to be unaffected by indomethacin pretreatment whereas diethylcarbamazine‐pretreatment markedly inhibited release.
The coronary vasoconstriction induced by Paf (0.9 nmol) was attenuated by pretreatment with indomethacin or diethylcarbamazine, whereas FPL 55712 caused a marked inhibition of the response. In contrast, the decrease in cardiac contractility was prevented by indomethacin or diethylcarbamazine and unaffected by FPL 55712 pretreatment.
It is concluded that LTC4 may be largely responsible for the coronary vasoconstriction induced by Paf with cyclo‐oxygenase products having a possible modulatory role whereas the latter appear to be involved in the Paf‐induced decrease in cardiac contractility.
Comparison of potency of α2‐adrenoceptor antagonists in vitro: evidence for heterogeneity of α2‐adrenoceptors
Authors: Alabaster V.A. , Keir R.F. , Peters C.J. 
Published: July 2012

A comparison has been made of affinity of α‐adrenoceptor antagonists for α2 binding sites in radioligand binding assays, and functional antagonist activity at pre‐ and postjunctional α2‐adrenoceptors in various in vitro preparations.
The antagonists displaced [3H]‐rauwolscine from rat brain and rabbit spleen membranes but there were substantial differences in rank order and absolute potency in the two tissues.
pA2 values for yohimbine, phentolamine and Wy26703 against the selective α2 agonist UK‐14,304 were determined in the rat left atrium, rat and rabbit vas deferens and rabbit saphenous vein preparations. The pA2 values varied substantially between the tissues, differing by two orders of magnitude in the case of Wy26703. Yohimbine was more potent in rabbit preparations while Wy26703 was markedly more potent in all the rat preparations.
Yohimbine and Wy26703 were compared in the dog saphenous vein preparation where pre‐ and postjunctional α2 antagonist activity can be compared in the same tissue. As in the rabbit preparations, yohimbine was more potent than Wy26703 at both sites but the absolute potencies were different.
It is concluded that α2‐adrenoceptors are a heterogeneous population, different subgroups being more apparent between species rather than between tissue types or location.
Quantification of the actions of agonists that simultaneously act on a particular type of receptor and have separate functional interactant properties
Authors: Goodall Jacqueline , Hughes I.E. , Mackay D. 
Published: July 2012

Null equations have been derived which allow quantification of the agonist properties of a compound that is able to modify the state of a tissue simultaneously by interacting with a particular type of receptor and by other means.
Parameters can be estimated which separately characterize the agonist properties of the compound and its functional interactant effect.
The null equations have been tested in a model system by using a mixture of papaverine (5 μM) and hexyltrimethylammonium bromide (30 μM) to mimic an agonist which also has functional antagonist properties.
The values obtained for the various parameters measured directly and indirectly are in good general agreement, confirming the validity of the model.
Meptazinol has a similar agonist action on opioid receptors in field‐stimulated mouse vas deferens and guinea‐pig ileum
Authors: Goodall Jacqueline , Hughes I.E. , Mackay D. 
Published: July 2012

The effects of the opioid receptor agonist RX783006 and of the opioid receptor partial agonist (+)‐meptazinol have been examined on electrically induced twitch responses of the guinea‐pig isolated ileum and of the mouse isolated vas deferens.
Log10 concentration‐tissue state curves were determined for (+)‐meptazinol and RX783006, alone, in combination and in the presence of naloxone (30 nM).
Analysis of these log10 concentration‐tissue state curves using the null equations derived and tested in the preceding paper indicates that the opioid agonist action of (+)‐meptazinol on mouse vas deferens is quantitatively similar to that on guinea‐pig ileum.
The results also suggest that (+)‐meptazinol acts as a functional antagonist on the guinea‐pig ileum as well as on the mouse vas deferens.
The potency of (+)‐meptazinol relative to RX783006 has been measured by an indirect method which should eliminate any functional antagonistic action of (+)‐meptazinol. This method gives a relative potency of (+)‐meptazinol in both tissues which is three to six times greater than that measured directly on guinea‐pig ileum. This discrepancy may be due to experimental error but it may also indicate that direct measurements on guinea‐pig ileum underestimate the agonist potency of this compound on opioid receptors.
α2‐Adrenoceptor‐mediated contractile response to catecholamines in smooth muscle strips isolated from rainbow trout stomach (Salmo gairdneri)
Authors: Kitazawa Takio , Kondo Hiroshi , Temma Kyosuke 
Published: July 2012

The type of adrenoceptor involved in the contractile response to catecholamines in smooth muscle strips isolated from rainbow trout stomach was determined.
Noradrenaline (10 nM‐10 μM) and adrenaline (10 nM‐3 μM) caused non‐sustained contractions which were markedly decreased by phentolamine (5.4 μM) but not by carteolol (5 μM). Phenylephrine (1 μM‐1 mM) was less effective in causing muscle contraction and methoxamine produced no contraction. Clonidine (100 nM‐300 μM) caused no mechanical response but inhibited the contraction to noradrenaline or adrenaline but not acetylcholine or 5‐hydroxytryptamine.
Yohimbine (10 nM‐1 μM) decreased the contraction induced by noradrenaline or adrenaline but prazosin (1 μM) did not.
Tetrodotoxin (780 nM) partially reduced the contraction induced by noradrenaline or adrenaline but atropine (500 nM) did not.
In the presence of atropine (1 μM), electrical transmural stimulation caused frequency‐dependent, tetrodotoxin‐sensitive contractions.
These results suggest that the contractile response induced by noradrenaline or adrenaline is mediated by α2‐adrenoceptors. It is also suggested that noradrenaline and adrenaline contract the smooth muscle by direct action and by indirect action through the non‐cholinergic excitatory nerve.
5‐Methoxy‐N,N‐dimethyltryptamine‐induced analgesia is blocked by α‐adrenoceptor antagonists in rats
Authors: Archer Trevor , Danysz Wojciech , Jonsson Gösta , Minor Bruce G. , Post Claes 
Published: July 2012

The effects of the α‐adrenoceptor antagonists prazosin, phentolamine and yohimbine upon 5‐methoxy‐N,N‐dimethyltryptamine (5‐MeODMT)‐induced analgesia were tested in the hot‐plate, tail‐flick and shock‐titration tests of nociception with rats.
Intrathecally injected yohimbine and phentolamine blocked or attenuated the analgesia produced by systemic administration of 5‐MeODMT in all three nociceptive tests. Intrathecally administered prazosin attenuated the analgesic effects of 5‐MeODMT in the hot‐plate and tail‐flick tests, but not in the shock titration test.
Intrathecal yohimbine showed a dose‐related lowering of pain thresholds in saline and 5‐MeODMT‐treated animals. Phentolamine and prazosin produced normal dose‐related curves in the hot‐plate test and biphasic effects in the shock titration and tail‐flick tests.
These results demonstrate a functional interaction between α2‐adrenoceptors and 5‐HT agonist‐induced analgesia at a spinal level in rats.
Effects of opioid peptides and morphine on histamine‐induced catecholamine secretion from cultured, bovine adrenal chromaffin cells
Authors: Livett Bruce G. , Marley Philip D. 
Published: July 2012

The effect of opioid peptides and morphine on histamine‐induced catecholamine secretion has been studied in monolayer cultures of dispersed, bovine adrenal chromaffin cells.
Histamine‐induced a dose‐dependent secretion of both adrenaline and noradrenaline with a threshold dose of approximately 5 nM, an EC50 of 150 nM and maximal secretion at 10 μM.
Catecholamine secretion induced by 1 μM histamine was completely dependent on extracellular calcium, was inhibited in a dose‐dependent manner by mepyramine (1 nM‐1 μM), and was unaffected by cimetidine (10 μM) and hexamethonium (0.1 mM).
Dynorphin‐1–13 (1 nM‐20μM), metorphamide (0.1 nM‐10μM), morphine (1 nM − 0.1 mM) and diprenorphine (1 nM − 0.1 mM) each had no effect on adrenaline or noradrenaline secretion induced by 1 μM histamine.
The characteristics of histamine‐induced catecholamine secretion from bovine adrenal chromaffin cells were similar to those reported previously for cat and rat adrenal medulla being calcium‐dependent and mediated by H1 histamine‐receptors. The results with opioid peptides and morphine suggest that endogenous adrenal opioid peptides do not act on the opioid binding sites found on adrenal medullary chromaffin cells to modify their secretory response to histamine.
Pharmacological modulation of the effects of N‐formyl‐L‐methionyl‐L‐leucyl‐L‐phenylalanine in guinea‐pigs: involvement of the arachidonic acid cascade
Authors: Boukili M. Abdelhakim , Bureau Michel , Lagente Vincent , Lefort Jean , Lellouch‐Tubiana Arielle , Malanchère Evelyne , Vargaftig B. Boris 
Published: July 2012

The intravenous administration of the chemotactic and secretagogue peptide N‐formyl‐L‐methionyl‐L‐leucyl‐L‐phenylalanine (FMLP; 0.3–30 μg kg−1) to the guinea‐pig induces bronchoconstriction and dose‐dependent leukopenia accompanied by mild thrombocytopenia. No electron microscopic evidence of platelet aggregation in lungs or significant accumulation of 111In‐labelled platelets in the thoracic region at the height of bronchoconstriction was noted.
Bronchoconstriction and leukopenia induced by FMLP were not affected by prostacyclin, by platelet depletion, by the platelet‐activating factor (Paf‐acether) antagonist BN 52021 or by the histamine H1‐antagonist mepyramine. Bronchoconstriction, but not leukopenia, was inhibited by aspirin, whereas the peptido‐leukotriene antagonist compound FPL 55712 and the cyclo‐oxygenase lipoxygenase inhibitor indomethacin reduced bronchoconstriction to a limited extent only. The mixed cyclo‐oxygenase/lipoxygenase inhibitor compound BW 755C was very effective in blocking bronchoconstriction by the highest dose of FMLP used, but failed to interfere with leukopenia.
FMLP‐induced dose‐dependent contraction of parenchymal lung strips was accompanied by the formation of immuno‐reactive thromboxane B2 in amounts markedly less than those formed from exogenous arachidonic acid at concentrations equieffective in inducing contractions.
FMLP‐induced contractions of the guinea‐pig lung strip were not modified by mepyramine nor by FPL 55712. They were reduced by indomethacin and aspirin and an even greater reduction was obtained with aspirin used in combination with FPL 55712. BW 755C suppressed the effects of all the concentrations of FMLP tested, whereas tert‐butyloxy‐carbonyl‐L‐methionyl‐L‐leucyl‐L‐phenylalanine, a chemical analogue of FMLP, displaced the concentration‐response curve to the right, without reducing the maximal contraction obtained.
The present results indicate that: (a) bronchoconstriction by FMLP is not due to platelet activation, to cyclo‐oxygenase‐dependent mechanisms or to peptido‐leukotriene formation. The inhibitory effect of aspirin and BW 755C involves a property other than cyclo‐oxygenase inhibition, which is not shared by indomethacin. (b) The contractile effects of FMLP on parenchymal lung strips follow an interaction with specific receptor sites, as shown by the effectiveness of tert‐butyloxy‐carbonyl‐L‐methionyl‐L‐leucyl‐L‐phenylalanine, and involves the combined effects of cyclo‐oxygenase and lipoxygenase metabolites.
Electrical and mechanical effects of BRL34915 in guinea‐pig isolated trachealis
Authors: Allen S.L. , Boyle J.P. , Cortijo J. , Foster R.W. , Morgan G.P. , Small R.C. 
Published: July 2012

BRL34915 (0.1–10 μM) suppressed the spontaneous tone of guinea‐pig isolated trachealis in a concentration‐dependent manner. BRL34915 was not antagonized by propranolol (1 μM).
In trachea where spontaneous tone was suppressed by indomethacin (2.8 μM) but subsequently restored to the same level with acetylcholine or histamine, the relaxant potency of BRL34915 was reduced.
In Krebs solution containing K+ (120 mM), isolated trachealis muscle developed near‐maximal tension. The relaxant effects of BRL34915 were virtually abolished in this medium.
Concentration‐effect curves for KCl, acetylcholine and histamine were constructed in tissues treated with indomethacin (2.8 μM). BRL34915 (10 μM) depressed the foot of the concentration‐effect curve for KCl and caused minor rightward shifts in the concentration‐effect curves of acetylcholine and histamine.
Four K+‐channel inhibitors were tested. Apamin (0.1 μM) did not modify the action of BRL34915. Tetraethylammonium (8 mM) had little effect but procaine (5 mM) and 4‐aminopyridine (5 mM) each significantly inhibited the relaxant action of BRL34915.
Intracellular electrophysiological recording showed that BRL34915 (0.1 μM) caused very minor relaxation and little, if any, electrical change. Higher concentrations (1–10 μM) evoked relaxation, suppression of spontaneous electrical slow waves and marked hyperpolarization of the trachealis cells. In the presence of TEA (8 mM) or procaine (5 mM) the hyperpolarization induced by BRL34915 was significantly reduced.
In trachealis skinned of its plasma membranes, tension development induced by Ca2+ (20 μM) was unaffected either by BRL34915 (10 μM) or by nicorandil (1 mM).
In studies of the efflux of 86Rb+ from muscle‐rich strips of trachea, BRL34915 (1 and 10 μM) increased the effux rate constant.
It is concluded that BRL34915 evokes relaxation of the trachealis by a mechanism that involves neither β‐adrenoceptor activation nor direct reduction of the sensitivity of the intracellular contractile machinery to cytosolic free Ca2+. The action of BRL34915 may depend on the opening of K+ channels in the plasma membrane which are permeable to 86Rb+. The opening of these channels, or the effects of their opening, may be reduced by K+‐channel inhibitors such as 4‐aminopyridine, procaine and TEA but not by apamin.