bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of nicotine on spontaneous contractions of cat urinary bladder in situ
Authors: Koley Biswanath , Koley Juthika , Saha Joy Krishna 
Published: July 2012

Nicotine and dimethyl‐phenylpiperazinium (DMPP) increased intravesicular pressure and then transiently depressed the spontaneous activity of the urinary bladder in chloralose anaesthetized cats.
Adrenaline (5–10 μg kg−1), noradrenaline (5–20 μg kg−1) and isoprenaline (40–50 μg kg−1) which depressed spontaneous urinary bladder activity, were antagonized by the β‐receptor blocking agent propranolol (1 mg kg−1). Phenylephrine (10–30 μg kg−1) was ineffective on the urinary bladder though it increased the systemic blood pressure. This latter effect was blocked by the α‐receptor blocking agent phentolamine (2 mg kg−1).
Acetylcholine (2–8 μg kg−1) caused a marked fall in systemic blood pressure, which was potentiated by physostigmine, but failed to produce any response on the intravesicular pressure even after physostigmine (50–100 μg kg−1) treatment.
ATP (2 mg kg−1) produced an increase in intravesicular pressure accompanied by a fall in systemic blood pressure. The increased intravesicular pressure was antagonized by quinidine (20 mg kg−1); however, the fall in blood pressure remained unaltered.
The increased intravesicular pressure induced by nicotine (20–40 μg kg−1) or DMPP (50–100 μg kg−1) was not affected by phentolamine (2 mg kg−1), propranolol (1 mg kg−1) or guanethidine (15–20 mg kg−1). Physostigmine (50–100 μg kg−1), hemicholinium 3 (2 mg kg−1) or atropine (1 mg kg−1) were also unable to affect the response to nicotine.
Hexamethonium (1 mg kg−1), reduced the amplitude of spontaneous bladder contractions and quinidine (20 mg kg−1) abolished the effect of nicotine.
Bilateral sectioning of the cervical sympathetic or hypogastric nerves did not alter the effect of nicotine or DMPP. Higher spinal cord transection (C1–C2) blocked the spontaneous, as well as the nicotine‐ and DMPP‐induced, contractions of the bladder.
It is concluded that the increase in intravesicular pressure induced by nicotine is atropine‐resistant and is not mediated either through adrenergic or cholinergic mechanisms. It is probable that a purinergic mechanism is involved, via the activation of P2‐receptors present in the urinary bladder.
Prostanoid synthesis by aortic rings in human blood: selective increase of prostacyclin mediated by a serum factor
Authors: Ritter J.M. 
Published: July 2012

Synthesis of vascular epoprostenol (PGI2) and platelet thromboxane (TX) A2 is influenced by the coagulation cascade in incompletely understood ways. To elucidate this, prostanoids were determined in human blood anticoagulated by different drugs and incubated with and without rat aortic rings. Control incubations were performed in Hanks balanced salt solution. PGI2 and TXA2 synthesis were assessed by radioimmunoassay of their stable hydrolysis products 6‐oxo‐prostaglandin (PG) F1α and TXB2.
Fresh aortic rings incubated in Hanks solution with a thrombin inhibitor (TCK) synthesized similar quantities of 6‐oxo‐PGF1α in the presence or absence of sodium citrate. In contrast, the intracellular calcium antagonist TMB‐8 inhibited 6‐oxo‐PGF1α synthesis.
In contrast to the finding in Hanks solution, sodium citrate inhibited 6‐oxo‐PGF1α synthesis by fresh aortic rings incubated in blood anticoagulated with TCK. However, TXB2 synthesis was not affected by citrate.
Blood incubated alone at 37°C in plain glass tubes generated a small amount of immunoreactive 6‐oxo‐PGF1α. A thromboxane synthase inhibitor, OKY1581, increased immunoreactive 6‐oxo‐PGF1α. However, blood anticoagulated with TCK and incubated similarly, generated no detectable 6‐oxo‐PGF1α either in the presence or absence of OKY1581, showing that 6‐oxo‐PGF1α synthesis in the previous experiments was dependent on the vascular rings.
OKY1581 had little or no effect on 6‐oxo‐PGF1α synthesis in incubations of fresh aortic rings with blood anticoagulated with TCK, despite inhibition of TXB2 synthesis. However, OKY1581 increased 6‐oxo‐PGF1α synthesis by rings pretreated with acetylsalicylic acid (ASA) when incubated in blood, presumably by diversion of platelet endoperoxide to vascular PGI2 synthase.
Sodium citrate did not influence the increase in 6‐oxo‐PGF1α synthesis by ASA pretreated aortic rings caused by OKY1581 in whole blood. This implies that the PGI2 stimulating activity of whole blood in the absence of citrate exerts its effect proximal to PGI2 synthase.
It is concluded that a low molecular weight serum factor formed during activation of the intrinsic coagulation pathway in blood, modulates PGI2/TXA2 balance by an action on vascular cyclooxygenase, possibly by an effect on intracellular calcium.
Neuropeptide Y potentiates the effect of various vasoconstrictor agents on rabbit blood vessels
Authors: Edvinsson Lars , Ekblad Eva , Håkanson Rolf , Wahlestedt Claes 
Published: July 2012

The contractile effect of neuropeptide Y (NPY) was tested on isolated segments of basilar artery, central ear artery, gastro‐epiploic artery and vein, and femoral artery and vein from the rabbit. At 30 nM NPY did not evoke vasoconstriction; at 300 nM NPY evoked a weak and variable response.
NPY greatly potentiated the response of the gastro‐epiploic and femoral arteries to noradrenaline without affecting the maximum response. As tested on the gastro‐epiploic artery NPY was effective at concentrations of 1 nM and higher. As tested on the femoral artery the potentiating effect of 30 nM NPY on noradrenaline‐evoked contractions was apparent immediately and 30 min after the application of NPY, but not after one hour.
NPY (30 nM) potentiated the contractile response to noradrenaline and histamine but not to 5‐hydroxytryptamine or high K+. The response to histamine was augmented in both arteries and veins, whereas the response to noadrenaline was enhanced in arteries but not in veins. NPY failed to potentiate the prostaglandin F2α‐evoked contraction except in the gastro‐epiploic vein.
An analysis of the purinergic component of active muscle vasodilatation obtained by electrical stimulation of the hypothalamus in rabbits
Authors: Shimada Steven G. , Stitt John T. 
Published: July 2012

In anaesthetized rabbits, electrical stimulation of the hypothalamus in areas analogous to the defence area in cats produces the ‘defence reaction.’ This response includes signs of arousal and a large increase in blood flow to skeletal muscle in the hind limb caused by a vasodilatation in the skeletal muscle vasculature.
The vasodilatation is a sympathetic response, and it is not dependent upon muscle activity in the hind limb.
The muscle vasodilatation is insensitive to α‐adrenoceptor, β‐adrenoceptor, cholinoceptor and histamine receptor antagonists.
Intra‐arterial injections of the purinoceptor agonists, adenosine triphosphate (ATP) and adenosine, mimic the vasodilatation produced by electrical stimulation.
The P1‐purinoceptor blocker, aminophylline, attenuates adenosine‐induced vasodilatation, but it does not affect the vasodilatation produced by ATP or hypothalamic stimulation.
The P2‐purinoceptor blocker, antazoline, attenuates the vasodilatation produced by both ATP and hypothalamic stimulation.
Our results suggest that the muscle vasodilatation produced by hypothalamic stimulation is mediated by purinergic nerves which release ATP and act on P2‐purinoceptors.
Sex and hormonal influences on platelet sensitivity and coagulation in the rat
Authors: Emms H. , Lewis G.P. 
Published: July 2012

Platelet sensitivity to adenosine di‐phosphate (ADP), thrombin, collagen, arachidonic acid and prostaglandin I2 (PGI2) and the activity of the coagulation system as measured by the activated partial thromboplastin time, prothrombin time, Russell's viper venom time and plasma fibrinogen have been examined in male and female rats, female rats during the oestrous cycle and female rats treated with oestrogen and a progestogen.
Male rat platelets were less sensitive to thrombin and more sensitive to inhibition by PGI2 than those from females and fibrinogen levels in male rat plasma were approximately twice those seen in females.
During the oestrous cycle, platelets were more sensitive to ADP and less sensitive to thrombin at dioestrus.
Following 6 weeks treatment with 17 β‐oestradiol or ethynyl oestradiol, both platelet aggregation and release of granular ATP induced by collagen were significantly reduced. Platelet sensitivity to other agents, ADP, arachidonic acid, thrombin and PGI2 was, however, unchanged following oestrogen treatment. Activation of factor X by Russell's viper venom was accelerated in rats treated with ethynyl oestradiol, although this enhancement was not reflected in the overall clotting times.
The isolated stomach preparation of the mouse: a physiological unit for pharmacological analysis
Authors: Black J.W. , Shankley N.P. 
Published: July 2012

Although oxyntic cell secretion can be studied at many organisation levels between isolated cell suspensions and non‐invasive techniques in animals, the isolated, lumen‐perfused, stomach preparation of the mouse represents a hierarchical level which eliminates extrinsic regulatory influences but retains all the cellular architecture known to be necessary for physiological responses and so can be defined as the physiological unit of acid secretion.
The feeding pattern before and the distending pressure during an experiment have been identified as the main determinants of basal secretion: the combination of an intragastric pressure of 12 cmH2O and the fasted state generated a stable basal secretion over 2 h providing a satisfactory basis for bioassays.
Basal acid secretion was lowered by treatment with omeprazole and sodium thiocyanate but not with tetrodotoxin, N‐methylatropine or tiotidine, suggesting that basal secretion does not involve nervous stimulation or the local release of histamine under these experimental conditions.
The improved assay permitted the full characterization of cumulative agonist concentration‐effect curves in single stomach preparations to histamine, 5‐methylfurmethide, pentagastrin and isobutylmethylxanthine.
Interestingly, pentagastrin produced sustained stimulation of gastric acid secretion under conditions when there was no pharmacological evidence that histamine secretion was taking place. This finding is discussed in relation to the role of histamine in the control of gastric acid secretion.
Pharmacological analysis of the pentagastrin‐tiotidine interaction in the mouse isolated stomach
Authors: Black J.W. , Leff P. , Shankley N.P. 
Published: July 2012

The pentagastrin‐tiotidine interaction has been analysed, using improved techniques, in the mouse isolated, lumen‐perfused, stomach assay. For comparison and quantification of the H2‐receptor blocking activity of tiotidine, histamine‐tiotidine interactions have also been analysed in the mouse stomach and guinea‐pig isolated right atrial preparation.
Tiotidine behaved as a competitive antagonist of histamine both in the guinea‐pig right atrium (pKB 7.57) and mouse stomach (pKB 6.96). The difference in pKB was attributed to the loss of tiotidine into the gastric secretion.
On the stomach assay, pentagastrin concentration‐effect curves were significantly flatter with lower maximal responses than those obtained to histamine. In addition the profile of inhibition observed with tiotidine was different in that the pentagastrin curve maxima were depressed with only a small concomitant dextrad shift.
A mathematical model has been developed which accounts for the differences in agonist concentration‐effect curves and describes in a quantitative manner the expectations for the competitive antagonism of endogenous histamine assumed to be released by pentagastrin. Fitting of the pentagastrin‐tiotidine data to this model provided a reasonable goodness‐of‐fit.
The results are discussed in terms of the role of endogenous histamine in gastrin‐stimulated acid secretion. We conclude that the results are consistent with the hypothesis that pentagastrin stimulates acid secretion via the release of endogenous histamine under the present experimental conditions.
Evidence that the accumulation of 5‐hydroxytryptamine in the liver but not in the brain may cause the hypoglycaemia induced by 5‐hydroxytryptophan
Authors: Endo Yasuo 
Published: July 2012

Experiments were undertaken to determine whether the site of the hypoglycaemic action of 5‐hydroxytryptophan (5‐HTP), a direct precursor of 5‐hydroxytryptamine (5‐HT), was in the central nervous system or in the liver.
The fall in blood glucose followed the rapid increase in the amount of 5‐HT both in the brain and liver after 5‐HTP injection into pargyline‐treated and non‐treated mice.
Carbidopa, an inhibitor of peripheral aromatic amino acid decarboxylase, prevented the elevation of 5‐HT levels in the liver of both pargyline‐treated and non‐treated mice. In contrast, carbidopa did not prevent but rather enhanced the elevation of 5‐HT levels in the brain of both groups of mice.
Corresponding to the prevention of 5‐HT elevation in the liver, the fall in blood glucose was prevented by carbidopa.
These results support the idea that the accumulation of 5‐HT in the liver but not in the brain causes the hypoglycaemia induced by 5‐HTP.
Carbachol and dibutyryl cyclic GMP on the vulnerability to ventricular fibrillation in rat isolated hearts
Authors: Daugherty Alan , Woodward Brian 
Published: July 2012

cyclic monophosphate (cyclic GMP) concentrations may increase electrical stability of the myocardium was examined by determination of ventricular fibrillation thresholds (VFT) on isolated perfused hearts of the rat. Hearts were paced to circumvent any complicating effects of bradycardia. Using this system, carbachol produced a concentration‐related reduction in VFT.
The reduction in VFT produced by carbachol was not significantly modified by a high concentration of atenolol (10−5 M), indicating that the increased vulnerability to ventricular fibrillation was not an indirect consequence of catecholamine release from intramyocardial stores.
Atropine (10−6 M) blocked the carbachol‐induced reduction in VFT.
At the concentrations of carbachol used to reduce VFT, myocardial cyclic GMP concentrations were also elevated. The dibutyryl analogue of cyclic GMP (10−4 M) mimicked the effect of carbachol in reducing VFT.
Carbachol potentiated the adrenaline (3 × 10−7 M)‐induced reduction in VFT.
The ability of thapsigargin and thapsigargicin to activate cells involved in the inflammatory response
Authors: Ali H. , Christensen S. Brøgger , Foreman J.C. , Pearce F.L. , Piotrowski W. , Thastrup O. 
Published: July 2012

The ability of thapsigargin and thapsigargicin to activate mast cells and leukocytes has been investigated.
The thapsigargin‐induced histamine release from rat peritoneal mast cells was found to be dependent on the concentration of thapsigargin, the purity of the mast cell preparations, and the number of mast cells in suspension.
Thapsigargin induced histamine release from human basophil leukocytes.
Thapsigargin induced β‐glucuronidase and lysozyme release from human neutrophil leukocytes.
Thapsigargin caused a release of histamine from mesentery, lung, and heart mast cells of the rat, but only to a minor extent from the corresponding guinea‐pig cells.
Thapsigargicin induced histamine release from mesentery, lung, and heart mast cells of the rat at concentrations from 0.1 μM but provoked only a release from the corresponding guinea‐pig cells in the concentration‐range 0.16 to 1.6 μM.
Thapsigargin increased the cytoplasmic free calcium level in intact human blood platelets at concentrations from 3.0 nM
Opioid inhibition of synaptic transmission in the guinea‐pig myenteric plexus
Authors: Cherubini E. , Morita K. , North R.A. 
Published: July 2012

Intracellular recordings were made from neurones in the myenteric plexus of the guinea‐pig ileum. Presynaptic nerves were excited by a focal stimulating electrode on an interganglionic strand.
Fast excitatory postsynaptic potentials (e.p.s.ps) were depressed in amplitude by morphine and [Met5]enkephalin in the concentration range of l nM‐l μM. Nicotinic depolarizations evoked by exogenously applied acetylcholine (ACh) were not affected by these opioids.
Hyperpolarization of the presynaptic fibres probably contributed to the depression of the fast e.p.s.p. because fast e.p.s.ps evoked by low stimulus voltages were more depressed than those evoked by high stimulus voltages and fast e.p.s.ps resulting from activation of a single presynaptic fibre were blocked in a non‐graded manner.
Opioids depressed the slow e.p.s.p. in those neurones in which they did not change the resting membrane potential.
The slow e.p.s.p. was increased in amplitude in those neurones hyperpolarized by opioids. Depolarizations resulting from application of barium, substance P or ACh were also enhanced by opioids. Equivalent circuit models in which opioids increase, and substance P or ACh decrease, the same potassium conductance could account for this enhancement.
The actions of opioids were prevented or reversed by naloxone (l nM‐l μM).
It is concluded that morphine and enkephalin inhibit the release of ACh and a non‐cholinergic transmitter from fibres of the myenteric plexus, and that this may involve a hyperpolarization of presynaptic fibres. Additionally, opioids can interact postsynaptically with other substances which affect membrane potassium conductances.
Pharmacological basis for the induction of gastric carcinoid tumours in the rat by loxtidine, an unsurmountable histamine H2‐receptor blocking drug
Authors: Brittain R.T. , Jack D. , Reeves J.J. , Stables R. 
Published: July 2012

The very late occurrence of gastric carcinoids in a life‐span carcinogenicity study with loxtidine in the rat might have resulted from continuous achlorhydria induced by this long‐acting unsurmountable histamine H2‐antagonist.
The nature of the anti‐secretory activity of loxtidine was compared with that of ranitidine on histamine‐induced acid secretion in the perfused stomach preparation of the rat and in the rat isolated gastric mucosa preparation.
Ranitidine and loxtidine had qualitatively different inhibitory effects on acid secretion, ranitidine being a competitive antagonist of histamine even at high concentrations, whereas the effect of loxtidine on both preparations was unsurmountable at relatively low concentrations.
These results support the hypothesis that the late formation of gastric carcinoids in rats receiving loxtidine is a consequence of persistent achlorhydria caused by unsurmountable blockade of parietal cell H2‐receptors.
Bay K 8644, a dihydropyridine calcium agonist, augments vasoconstrictor responses to endogenous and exogenous noradrenaline in the peripheral vasculature of the dog
Authors: Goto Toshikazu , Satoh Keisuke , Taira Norio 
Published: July 2012

The effect of Bay K 8644 (a substance known to increase calcium influx through the voltage‐dependent calcium channel) on vasoconstrictor responses of resistance vessels to endogenous and exogenous noradrenaline (NA) was investigated in pentobarbitone‐anaesthetized dogs which had also undergone spinal anaesthesia and bilateral vagotomy and received atropine.
In these dogs the saphenous arterial bed was perfused at fixed flow rates with autologous blood to give perfusion pressure close to the systemic blood pressure.
Electrical stimulation (3–30 Hz) of the saphenous nerve and single intra‐arterial (i.a.) injections of noradrenaline (NA, 0.03‐3 μg) produced an increase in perfusion pressure (vasoconstriction) in a frequency‐ and a dose‐dependent manner, respectively.
Intra‐arterial infusions of Bay K 8644 (3 and 10 μg min−1) per se produced no significant change in perfusion pressure. However, these infusions augmented vasoconstrictor responses to both saphenous nerve stimulation (endogenous NA) and i.a. NA (exogenous NA).
These results suggest that augmentation by Bay K 8644 of vasoconstrictor responses of resistance vessels to endogenous and exogenous NA is probably due to promotion of the calcium influx through calcium channels closely associated with α‐adrenoceptors in smooth muscle cells there.
Identification of presynaptic β2‐adrenoceptors on the sympathetic nerve fibres of the human pulmonary artery
Authors: Göthert Manfred , Hentrich Frank 
Published: July 2012

Strips of human pulmonary arteries from patients undergoing surgery for lung tumour were incubated with [3H]‐noradrenaline. Subsequently, they were supervised with physiological salt solution containing cocaine and corticosterone. Tritium overflow from the strips was stimulated by transmural electrical impulses (2 Hz). The electrically evoked overflow of tritium consisted of 91% unmetabolized [3H]‐noradrenaline, and this percentage was not altered by isoprenaline.
Adrenaline (in the presence of rauwolscine), isoprenaline and the preferential β2‐adrenoceptor agonist, procaterol, concentration‐dependently increased the electrically evoked tritium overflow. Prenalterol, a β‐adrenoceptor agonist with moderate preference for β,‐adrenoceptors, was considerably less active than the previously mentioned agonists; noradrenaline (in the presence of rauwolscine) was ineffective.
The concentration‐response curve of procaterol was shifted to the right by the preferential β2‐adrenoceptor antagonist ICI 118–551 but was not affected by the β1‐selective antagonist, atenolol. Propranolol, but not atenolol, produced a shift to the right of the concentration‐response curve of isoprenaline.
It is concluded that the sympathetic nerve fibres of the human pulmonary artery are endowed with facilitatory presynaptic β2‐adrenoceptors.