bluuebunny/crossref_metadata_2025_split huggingface dataset:
STIMULATORY AND INHIBITORY HISTAMINE RECEPTORS IN CANINE CYSTIC DUCT
Authors: CLANACHAN A.S. , COURTNEY D.R , SCOTT G.W. 
Published: July 2012

The effects of histamine receptor stimulation were assessed on the resistance of the canine cystic duct in vivo and on the contractility of circular muscle preparations of canine cystic duct in vitro.
In anaesthetized dogs, the H1‐receptor agonist, 2‐pyridylethylamine (0.05 to 15 μmol, i.a.), elicited dose‐dependent increases in cystic duct resistance, whereas the H2‐receptor agonist, 4‐methylhistamine (0.05 to 15 μmol, i.a.) decreased cystic duct resistance. These responses were antagonized by the H1‐receptor antagonist, diphenhydramine, and the H2‐receptor antagonist, cimetidine, respectively.
Histamine (0.1 to 3000 nmol, i.a.) also increased cystic duct resistance in vivo. In the presence of diphenhydramine, the stimulatory effect of histamine was antagonized and slight decreases in cystic duct resistance became apparent. Cimetidine or prazosin also antagonized the stimulatory effects of histamine.
Histamine (1 to 100 μm) or 2‐pyridylethylamine (1 to 100 μm) contracted, whereas 4‐methylhistamine (1 to 100 μm) relaxed, circular muscle preparations of cystic duct. These excitatory and inhibitory responses were antagonized by diphenhydramine and cimetidine, respectively.
These results indicate that the canine cystic duct possesses excitatory H1‐ and inhibitory H2‐receptors. The predominant effect of histamine is an H1‐receptor‐mediated increase in cystic duct resistance. Histamine, which may be released in association with cholecystitis, may exert significant effects on the regulation of bile flow in and out of the gallbladder and may contribute to gallbladder stasis during biliary disease.
DIRECT AND INDIRECT EFFECTS OF ADENOSINE 5′‐TRIPHOSPHATE ON GUINEA‐PIG ILEUM
Authors: WATT A.J. 
Published: July 2012

The inhibitory effects of adenosine 5′‐triphosphate (ATP) were compared on the responses to electrical stimulation, and to direct and indirect stimulation by drugs of the longitudinal smooth muscle of guinea‐pig ileum before and after blocking nervous activity.
While the major inhibitory effect of ATP was an indirect one on the intramural excitatory nerves, there was also a small direct effect on the muscle.
ATP also had direct and indirect excitatory effects. The direct effect particularly was only seen with high concentrations of ATP, but the appearance of these excitatory effects may be affected by the inhibitory actions.
Antiarrhythmic actions of meptazinol, a partial agonist at opiate receptors, in acute myocardial ischaemia
Authors: Fagbemi Olu , Kane Kathleen A. , Leprán Istvan , Parratt James R. , Szekeres Laszlo 
Published: July 2012

The intravenous administration, to anaesthetized rats, of meptazinol (1 and 2 mg kg−1), a partial agonist at opiate receptors, greatly reduced the incidence of ventricular extrasystoles that resulted from acute coronary artery occlusion. The incidence of ventricular fibrillation (VF) was reduced from 50% (in the controls) to 10% and the mortality from 30% to zero.
In similar doses, pretreatment with meptazinol also reduced ventricular arrhythmias, including fibrillation, in conscious rats subjected to coronary artery occlusion. In this model, survival at 16 h was increased from 27% in the controls to 50% and 83% respectively in rats pre treated with 1 and 2 mg kg−1 of the drug.
In antiarrhythmic doses, meptazinol had little effect on either heart rate or systemic arterial blood pressure.
Intracellular action potential recordings from papillary muscle removed from rats given meptazinol (2 mg kg−1) 15 min previously showed an increase in APD50 and APD90 of more than 40%. There was no effect on dV/dtmax. When superfused with meptazinol in vitro normal rat papillary muscle stimulated at 1 or 3 Hz showed an increase in APD90 and a decrease in dV/dtmax.
The antiarrhythmic effect of meptazinol in these models can probably be explained by direct actions on the cardiac muscle action potential (increase in APD) although effects on opiate receptors cannot be ruled out. It is suggested that meptazinol might be useful in relieving pain, and in reducing the severity of arrhythmias in the early stages of acute myocardial infarction.
Contractions induced by grayanotoxin I in the guinea‐pig vas deferens
Authors: Ohizumi Yasushi 
Published: July 2012

In the guinea‐pig vas deferens, grayanotoxin I (G‐I), a diterpenic toxin isolated from certain ericaceous plants caused rhythmic contractions which were dose‐dependent (5 × 10−5 m — 10−3 m); these followed an initial transient contraction.
The G‐I (3 × 10−4 m)‐induced contraction was markedly inhibited or abolished by reserpine (2 mg/kg on 2 days), phentolamine (2 × 10−7 m and 10−6 m) or tetrodotoxin (TTX, 5 × 10−7 m), but remained almost unaffected by atropine (10−6 m) or mecamylamine (3 × 10−5 m). This contraction was also abolished after storage at 4°C for 7 days or incubation in Na‐deficient or Ca‐free medium.
After treatment with G‐I (3 × 10−5 m), which did not alter the tension of the preparation, transmural stimulation (10–50 Hz, 0.5 ms, supramaximal voltage, for 3 s) induced a slower contraction (second contraction) following the first rapid contraction caused by stimulation.
The second contraction was inhibited or abolished by reserpine (2 mg/kg on 2 days), phentolamine (2 × 10−7 m and 10−6 m) and TTX (2 × 10−8 m), but was not affected by atropine (10−6 m) and mecamylamine (3 × 10−5 m).
G‐I (3 × 10−5 m) shifted the dose‐response curves for noradrenaline (NA), acetylcholine and high‐K contractions to the left in a parallel manner and slightly increased the maximal response to these agonists.
G‐I (3 × 10−4 m) caused a release of endogenous NA from the vas deferens which was approximately 120 times that of control preparations. This response was inhibited or abolished by TTX (5 × 10−7 m) or incubation in Ca‐free medium.
These results suggest that the G‐I‐induced contraction of the vas deferens and the G‐I‐induced second contraction on electrical stimulation are the result of an indirect action mediated through the release of NA from the adrenergic nerve endings.
Effects of prostaglandin I2 and carbocyclic thromboxane A2 on smooth muscle cells and neuromuscular transmission in the guinea‐pig mesenteric artery
Authors: Makita Yuji 
Published: July 2012

In the guinea‐pig mesenteric arteries neither prostacyclin (PGI2) nor carbocyclic thromboxane A2 (cTxA2) affected membrane potential in concentrations below 1 × 10−6 m. Increasing the concentration to 3 × 10−6 m either slightly hyperpolarized or depolarized the membrane with little change in membrane resistance.
At a concentration of 1 × 10−7 m, the amplitude of the first e.j.p. and the enlarged amplitudes of the subsequent e.j.ps evoked by trains of stimuli were reduced consistently by PGI2 or cTxA2. Facilitation was unaffected by either agent.
The inhibitory actions of PGI2 were partly overcome by increased concentrations of 5 mm [Ca]o and were accelerated by a reduced concentration of 1.25 mm [Ca]o.
The amplitude of the contraction evoked by perivascular nerve stimulation was inhibited to a greater extent by PGI2 than by cTxA2 at concentrations below 1 × 10−6 m.
The contraction evoked by 5 × 10−6 m noradrenaline (NA) or excess concentrations of 20.2 mm [K]o was enhanced by 1 × 10−8 m — 1 × 10−6 m cTxA2 and suppressed by 1 × 10−8 m — 1 × 10−6 m PGI2. The minimum concentration of cTxA2 required to produce the contraction was 1 × 10−8 m.
These results indicate that transmission at the neuromuscular junction was inhibited consistently by PGI2 or cTxA2, presumably due to inhibition of NA release by suppression of the Ca influx at the nerve terminals. Whereas PGI2 inhibited, cTxA2 enhanced the mechanical response by a direct action on the smooth muscle cells.
The release of prostanoids during the acute pulmonary response to E. coli endotoxin in anaesthetized cats
Authors: Coker Susan J. , Hughes Bernadette , Parratt J.R. , Rodger I.W. , Zeitlin I.J. 
Published: July 2012

The administration of E. coli endotoxin (2 mg/kg i.v.) to anaesthetized cats results in a characteristic acute pulmonary response. This consists of increases in pulmonary artery pressure and airways resistance and a reduction in lung compliance.
Plasma concentrations of prostaglandin E2 (PGE2), PGF2α, thromboxane B2 and 6‐keto PGF1α were measured by radioimmunoassay in aortic and pulmonary arterial blood samples before, during and after the acute pulmonary response to endotoxin.
Endotoxin administration resulted in the rapid release of PGF2α and thromboxane B2 from the lungs. The time course of this release was parallel to that of the pulmonary hypertensive and airways responses to endotoxin. PGE2 and 6‐keto PGF1α were released more gradually and with greater variations between individual animals.
During the delayed shock phase (2 h after endotoxin) the concentrations of PGE2, PGF2α and 6‐keto PGF1α were once again elevated in both the aorta and pulmonary artery. Thromboxane B2 concentrations were not increased at this time.
These results suggest that PGF2α and thromboxane A2 may be mediators of the acute pulmonary responses to endotoxin.
Presynaptic α2‐adrenoceptor antagonism by verapamil but not by diltiazem in rabbit hypothalamic slices
Authors: Galzin Anne‐Marie , Langer S.Z. 
Published: July 2012

Rabbit hypothalamic slices prelabelled with [3H]‐noradrenaline and superfused with Krebs solution were stimulated electrically at a frequency of 5 Hz. Exposure to verapamil (0.1 to 10 μm) significantly increased, in a concentration‐dependent manner, the electrically‐evoked overflow of tritium, without affecting the spontaneous outflow of radioactivity.
Exposure to diltiazem in concentrations up to 100 μm had no effect on the electrically evoked release of [3H]‐noradrenaline, but increased the basal outflow of radioactivity at 10 and 100 μm.
The preferential α2‐adrenoceptor antagonist, yohimbine (0.1 μm) significantly antagonized the inhibitory effect of clonidine or adrenaline on [3H]‐noradrenaline overflow elicited by electrical stimulation. Verapamil (3 μm) also antagonized this inhibitory effect of the α2‐adrenoceptor agonists on [3H]‐noradrenaline release. In contrast to these results, exposure to diltiazem (10 μm) was ineffective in blocking the action of the α2‐adrenoceptor agonist.
These results suggest that the two Ca2+‐antagonists verapamil and diltiazem differ in their ability to affect central noradrenergic neurotransmission. While verapamil is a relatively potent α2‐adrenoceptor antagonist, diltiazem is devoid of presynaptic α2‐adrenoceptor antagonist properties.
Modulation of transmission in rat sympathetic ganglia by activation of presynaptic α‐ and β‐adrenoceptors
Authors: Medgett Iain C. 
Published: July 2012

Conditions under which transmission in rat isolated superior cervical ganglia may be affected by activation of presynaptic α‐ and β‐adrenoceptors have been investigated by means of an extracellular recording method.
Clonidine caused a small hyperpolarization of the ganglia (mean EC50˜‐2 nm) in unstimulated preparations; with continuous preganglionic stimulation at 0.2 Hz, clonidine markedly decreased the height of the compound action potential (mean EC50˜18 nm).
Phentolamine (0.1–3 μm) per se increased the height of the compound action potential by up to 15%, and antagonized the inhibitory effects of adrenaline and clonidine.
Using a higher frequency of stimulation (0.5 Hz), the effect of phentolamine (1 μm) was unchanged, whereas the inhibitory effectiveness of adrenaline on the height of the compound action potential was reduced.
(±)‐Propranolol (0.1 μm) did not affect the height of the compound action potential, whereas the inhibitory effects of high concentrations of adrenaline were enhanced.
During an infusion of clonidine (1 μm), adrenaline (1–100 μm) and, less effectively, noradrenaline (10–100 μm) increased the height of the compound action potential by up to 14%; these effects were antagonized by propranolol (0.1 μm).
In the presence of noradrenaline (10 and 30 μm) adrenaline (100 μm) caused a small (up to 5%) enhancement of the height of the compound action potential.
The results obtained are consistent with the existence of presynaptic α‐ and β‐adrenoceptors on preganglionic terminals. The α‐adrenoceptor may be part of a trans‐synaptic inhibitory feedback mechanism; however the functional role of the facilitatory β‐adrenoceptor is not clear.
Influence of diabetes on the reactivity of mesenteric microvessels to histamine, bradykinin and acetylcholine
Authors: Fortes Zuleica B. , Leme J. Garcia , Scivoletto Regina 
Published: July 2012

Noradrenaline (NA) evoked a vasoconstrictor response in rat mesenteric microvessels in situ, the latency and nature of which was analogous in normal and alloxan‐diabetic animals.
Histamine and bradykinin (Bk) were capable of antagonizing the response to NA in normal but not in diabetic animals. In contrast, acetylcholine (ACh) was equally effective as an antagonist to NA in both groups of animals.
The altered responses to histamine and Bk were not associated with hyperglycaemia since fasting rendered the diabetic animals normoglycaemic and yet did not restore the reactivity of microvessels. Previous administration of insulin to diabetic animals corrected the impaired responses to histamine and Bk.
A similar condition of impaired responses to histamine and Bk was produced in normal animals by the intravenous injection of 2‐deoxyglucose although ACh remained fully active.
Apparently, the functional changes observed in the response to histamine or Bk, as antagonists of the vasoconstrictor reaction to NA, were not associated with a defective response of all smooth muscle. First, because ACh remained active in diabetic animals, and, second, because extravascular smooth muscles obtained from either normal or diabetic rats were equally relaxed by histamine or Bk in vitro.
It is suggested that histamine and Bk antagonized the vasoconstrictor response of microvessels to NA through an action on lining endothelial cells resulting in increased vascular permeability and hyperosmolarity of extracellular fluids.
The process depended on the availability of insulin, and, therefore, might be affected by intracellular glucopaenia as occurring in diabetes.
Intracellular glucopaenia markedly affected other structures. Reduced atria rates were observed in diabetes, despite the fact that the isolated preparation responded normally to NA, ACh or tyramine. Partial substitution of glucose in the bathing fluid by 2‐deoxyglucose or addition of NaF to the organ bath evoked similar changes in atria from normal animals.
ACh which has little effect on vascular permeability must exert its vasodilator effects through mechanisms which are different from those influenced by the biochemical changes occurring in diabetes.
Neostigmine augments responses of the rat anococcygeus muscle to field stimulation
Authors: Smith J. A. , Spriggs T.L.B. 
Published: July 2012

The effects of neostigmine on noradrenergic transmission have been studied in the field stimulated, isolated anococcygeus muscle of the rat.
In those muscles where the excitatory response to field stimulation was not completely inhibited by guanethidine (5 × 10−6 to 10−5m) or phentolamine (10−6m), atropine (5 × 10−8m) gave no further inhibition of the response.
The shape of the response to field stimulation was altered in a dose‐dependent manner by neostigmine (5 × 10−7 to 5 × 10−6m), such that a ‘shoulder’ appeared during the relaxation phase. The ‘shoulder’, present at all stimulation frequencies tested between 3 and 40 Hz, was abolished by atropine (5 × 10−8 M) and unaffected by tubocurarine (10−6 m).
Neostigmine (2.5 × 10−6 m), whether alone or in the presence of atropine (5 × 10−8 m), had no effect on the uptake or stimulation‐induced release of [3H]‐noradrenaline.
Using electron microscopy, small Schwann/axon bundles close to smooth muscle cells rarely showed Cholinesterase staining, whereas larger bundles at the outer serosal aspects of the muscle exhibited dense staining.
It is concluded that the observed effects of neostigmine are not due to a presynaptic effect on noradrenergic transmission.
An in vivo model for measuring antigen‐induced SRS‐A‐mediated bronchoconstriction and plasma S RS‐ A levels in the guinea‐pig
Authors: Anderson Wayne H. , O'Donnell Margaret , Simko Beverly A. , Welton Ann F. 
Published: July 2012

Pharmacological modulation of antigen‐induced anaphylaxis in actively sensitized guinea‐pigs with intravenously administered indomethacin (10 mg/kg), pyrilamine (2.0 mg/kg) and propranolol (0.1 mg/kg) resulted in a delayed onset, slowly developing bronchoconstriction indicative of a slow‐reacting substance of anaphylaxis (SRS‐A) response.
Measurements of pulmonary mechanics on the drug‐pretreated animals challenged with ovalbumin demonstrated a more prominent effect on dynamic compliance than resistance. This is consistent with the more potent effects of SRS‐A on peripheral rather than central airways.
The slowly developing bronchoconstriction obtained after treatment with indomethacin, pyrilamine and propranolol was inhibited by the standard SRS‐A antagonist, FPL 55712 and the SRS‐A synthesis inhibitors, phenidone, BW 755C and nordihydroguaiaretic acid.
Plasma SRS‐A levels were determined in guinea‐pigs following antigen challenge. The appearance of SRS‐A in the plasma preceded the onset of bronchoconstriction and SRS‐A levels remained elevated throughout its development. Coincident with the inhibition of bronchoconstriction by the SRS‐A synthesis inhibitor, phenidone, was a dose‐dependent reduction in plasma SRS‐A. The intravenous ED50 in each case was 4 mg/kg.
This model of antigen‐induced SRS‐A‐mediated bronchoconstriction should prove useful for the in vivo evaluation and development of therapeutics which regulate the synthesis of SRS‐A.
Selective inhibition of thromboxane B2 accumulation and metabolism in perfused guinea‐pig lung
Authors: Hoult J.R.S. , Robinson C. 
Published: July 2012

U46619, a prostaglandin H2 endoperoxide analogue and thromboxane A2 agonist, dose‐dependently inhibited accumulation and metabolism of thromboxane B2 in the isolated perfused lung of the guinea‐pig. At similar doses prostaglandins E1, E2, F2α, F2α, I2, 5,6‐trans‐PGE2 and 8‐iso‐PGE1 were ineffective.
U46619 did not affect accumulation and metabolism of prostaglandin F2α under similar conditions.
The pulmonary disposition of thromboxane B2, which occurs by uptake into pulmonary cells or binding to a specific macro molecular component, is mediated by a mechanism distinct from that handling prostaglandin F2α. The possible relevance of these findings to the pulmonary disposition of thromboxane A2 is discussed.
Indirect action of 5‐hydroxytryptamine on the isolated muscularis mucosae of the guinea‐pig oesophagus
Authors: Kamikawa Yuichiro , Shimo Yasuo 
Published: July 2012

The site of action of 5‐hydroxytryptamine (5‐HT) was examined on the isolated muscularis mucosae attached to the submucous plexus of the guinea‐pig oesophagus. Isotonic responses of the longitudinal muscularis mucosae were recorded.
5‐HT produced a transient contraction of the muscularis mucosae at concentrations higher than 3 μm. The contraction was rapid in onset, reaching a peak in about 15 s or less, and was restored to the basal level after 20 to 30 s without washing out 5‐HT. When the 5‐HT‐induced contraction faded to the basal tone, successive applications of 5‐HT no longer produced any contracture.
Nicotine (Nic), at concentrations higher than 10 μm, also produced a transient contraction which had a very similar pattern to that induced by 5‐HT. Again, the successive application of Nic no longer produced any contracture following prior treatment with Nic itself. However, the 5‐HT‐induced contraction was not modified by the presence of Nic.
Exogenously applied acetylcholine (ACh) produced a concentration‐dependent contraction of the muscularis mucosae, the 50% effective concentration (EC50) was 69 ± 5.6 nm. The contraction was sustained during incubation with ACh, and was not modified by prior treatment with 5‐HT or Nic.
The 5‐HT (100 μm)‐induced contraction was completely abolished by tetrodotoxin (0.2 μm) and atropine (0.2 μm). This means that the action is mediated by stimulating cholinergic nerves in the submucous plexus attached to muscularis mucosae. Moreover, the stimulating action of 5‐HT does not involve nicotinic receptors, since the action was not blocked by hexamethonium (100 μm).
Among several 5‐MT antagonists examined, methysergide (1 μm), ketanserin (1 μm) and morphine (100 μm) failed to modify the 5‐HT (100 μm)‐induced contraction significantly. Cinanserin (0.1–3 μm), cyproheptadine (3–100 nm) and phenoxybenzamine (0.1–3 μm) inhibited the 5‐HT‐induced contraction, in a concentration‐dependent manner, and each highest concentration abolished the response. However, none of these antagonists was specific for 5‐HT, but the Nic (100 μm) or ACh (0.1 μm)‐induced contractions were also inhibited by them.
The present results indicate that 5‐HT contracts the muscularis mucosae of the guinea‐pig oesophagus indirectly by stimulating cholinergic nerves in the submucous plexus, and has no direct action on the muscularis mucosae. In addition, the type of 5‐HT receptors responsible for the stimulant action may be different from those in other parts of the gastrointestinal tract, blood vessels or brain, because of the different effects of 5‐HT antagonists.
Occurrence of α1s‐adrenoceptors in the mouse but not in the rabbit isolated anococcygeus preparations
Authors: Coates Jill , Weetman D.F. 
Published: July 2012

Both Sgd 101/75 (4(2‐imidazoline‐amino‐2‐methylindazol‐chlorhydrate) and noradrenaline contracted anococcygeal preparations from the mouse and rabbit.
The maximal response to and sensitivity (EC30 values) of each drug on the mouse was similar, whereas in the rabbit, Sgd 101/75 was a partial agonist relative to noradrenaline (intrinsic activity 0.50) and the EC30 value was 14.5 times higher than for noradrenaline.
In both species, phenoxybenzamine (0.3 nm for 30 min followed by 20 washes over 30 min) reduced the effects of Sgd 101/75 preferentially. When noradrenaline was then added in the presence of a high concentration of Sgd 101/75 (400 μm), its maximum response and EC30 value were decreased in the rabbit, but not in the mouse.
When a range of concentrations of phenoxybenzamine (30 pm‐3μm for 30 min followed by 20 washes over 30 min) was tested, the maximum response of the rabbit anococcygeus to noradrenaline declined in a concentration‐dependent manner. Similar experiments in the mouse resulted in two distinct sensitivities of the maximum response of noradrenaline to phenoxybenzamine (at 0.3 and 300 nm).
The results indicate that noradrenaline acts on two receptors to contract the mouse anococcygeus (α1 and α1s‐adrenoceptors), but only one (α1‐adrenoceptor) in preparations derived from the rabbit.
Inhibition of gastric acid secretion by intracerebroventricularly administered prostaglandin E2 in anaesthetized rats
Authors: Puurunen Juhani 
Published: July 2012

The effect of intracerebroventricularly (i.c.v) administered prostaglandin E2 (PGE2) on gastric acid secretion was studied in anaesthetized rats.
Intracerebroventricular injections of 1 and 3 μg of PGE2 inhibited gastric acid secretion induced by insulin, electrical vagal stimulation and acetylcholine in a dose‐dependent manner.
Intravenous injections of 1, 3 and 10 μg of PGE2 had no effect on insulin‐stimulated gastric acid output.
The results indicate that upon i.c.v. administration PGE2 inhibits gastric acid secretion by acting centrally and not peripherally after leakage from the central nervous system.