bluuebunny/crossref_metadata_2025_split huggingface dataset:
Augmentation by external Mg ions of β‐adrenoceptor‐mediated actions in the longitudinal muscle of rat uterus
Authors: Maruta Keiji , Osa Takuro 
Published: July 2012

The longitudinal muscle isolated from the uterus of oestrogen‐treated rats was not spontaneously active in Locke solution, and electrical stimulation evoked phasic contraction. Isoprenaline (3 × 10−11‐10−8m) and dibutyryl cyclic AMP (db cyclic AMP, 0.1–0.8 mm) depressed the phasic contraction; the depression was enhanced in the presence of 0.6 mm Mg.
The contracture generated by 40 mm K was partially relaxed by isoprenaline (10−11‐10−8m) and db cyclic AMP (0.1–0.8 mm). Mg (0.6 mm) enhanced the isoprenaline‐induced relaxation, but not that induced by db cyclic AMP.
The membrane potential of the muscle was −61 mV, and electrical stimulation induced an action potential which consisted of spike and plateau components. Application of isoprenaline and db cyclic AMP mainly reduced the duration of the plateau potential. The effect was potentiated by 0.6 mm Mg.
The membrane was hyperpolarized, accompanied by a decrease in membrane resistance, when 10−8 m isoprenaline or 0.8 mm db cyclic AMP was applied. The effects of isoprenaline were prominently augmented in the presence of 1.2 mm Mg, while those of db cyclic AMP were slightly potentiated.
Forskolin (0.1 μm) or papaverine (10 μm) inhibited the phasic contraction and the K‐contracture. The effect on the phasic contraction was potentiated by 0.6 mm Mg, while that on the K‐contracture was not affected.
Forskolin shortened the action potential at 0.3 μm, and hyperpolarized the membrane with a decrease in membrane resistance at 3.0 μm. The membrane effects were augmented by 0.6 and 1.2 mm Mg, respectively.
It was hypothesized that external Mg ions could affect at least two processes involved in actions at β‐adrenoceptors on rat myometrium; receptor‐agonist interaction and cyclic AMP‐mediated inhibition of membrane excitability.
Tolerance to cromakalim in the rat uterus in vivo
Authors: Downing Sandra J. , Miller M. , Hollingsworth> M. 
Published: July 2012

Cromakalim (0.1 and 1 mg kg−1) produced inhibition of uterine contractions and falls in mean blood pressure in ovariectomized, non‐pregnant rats, the durations of which were dose‐dependent. Frequency of contractions was inhibited selectively compared to amplitude.
The durations of the uterine effect of cromakalim (1 mg kg−1), when given at 12 h intervals, were less after the second, third and fourth doses compared to the first dose in non‐pregnant rats. In ovariectomized rats treated from day 18 of pregnancy, using the same experimental design, no uterine relaxant effects were seen to the third and fourth doses. The timing of delivery and foetal viability were unaffected by cromakalim.
The sensitivity of the uterus to cromakalim was tested using small doses before and after three cromakalim doses (1 mg kg−1) given at 8 h intervals in non‐pregnant rats. This regime resulted in a 25 fold decrease in the sensitivity of the uterus to cromakalim.
Cromakalim can produce long‐lasting inhibition of uterine contractions in the rat after bolus i.v. dose but it exhibits little selectivity relative to its vasodepressor action and there appears to be tolerance to the uterine relaxant action of cromakalim in vivo.
Evidence that central 5‐hydroxytryptaminergic neurones are involved in the anxiolytic activity of buspirone
Authors: Carli M. , Prontera C. , Samanin R. 
Published: July 2012

A two‐compartment exploratory test was used to assess the role of central 5‐hydroxytryptaminergic neurones in the anxiolytic activity of buspirone in rats.
Buspirone 0.1 mg kg−1, administered subcutaneously 15 min before testing, significantly increased black‐white transitions (BWT) in control rats but had no effect in animals injected intra‐cerebroventricularly one week before with 150 μg 5,7‐dihydroxytryptamine (in 20 μl).
Infusion of buspirone in the median raphe (but not in the dorsal raphe) significantly enhanced BWT, at doses from 1 μg to 10 μg (in 0.5 μl). Buspirone 5 and 10 μg, but not 1 μg, administered in the median raphe, significantly enhanced motor activity of rats during the first 10 min of testing in the activity cages.
The effect on BWT of 5 μg buspirone in the median raphe was completely antagonized in animals which had received either 5,7‐dihydroxytryptamine intraventricularly, 150 μg (in 20 μl), one week before or an infusion of 0.1 μg (in 0.5 μl) (−)‐propranolol in the same area 5 min before. (−)‐Propranolol infused in the median raphe did not modify the effect of buspirone on locomotion.
Infusion of 5 μg buspirone (in 0.5 μl) in the median raphe significantly enhanced punished responses in a conflict test with no effect on unpunished responding. Buspirone infused in the dorsal raphe had no effect on punished or unpunished responding over a wide dose range.
The results indicate that at the relatively low dose used in the present study buspirone produces an anxiolytic effect by acting on central 5‐hydroxytryptaminergic neurones. It is likely that activation of 5‐hydroxytryptamine1A‐receptors in the median raphe is involved.
Inhibition by glibenclamide of the vasorelaxant action of cromakalim in the rat
Authors: Buckingham Robin E. , Hamilton Thomas C. , Howlett David R. , Mootoo Sheila , Wilson Campbell 
Published: July 2012

In rat isolated thoracic aortic rings pre‐contracted with noradrenaline (10−6 m), cromakalim (3 × 10−7‐3 × 10−5 m) produced concentration‐related relaxation. This effect was progressively inhibited by increasing concentrations of the anti‐diabetic sulphonylurea drug, glibenclamide (10−6‐10−5 m).
In rat isolated portal veins, cromakalim (3 × 10−8‐10−6 m) produced concentration‐related inhibition of the spontaneous contractive activity and glibenclamide (3 × 10−7‐3 × 10−6 m) prevented this inhibitory action in a concentration‐dependent manner.
In both rat aortic rings and portal veins, cromakalim (10−5 m) stimulated 86Rb efflux. Prior exposure to glibenclamide (10−7‐10−6 m) produced a concentration‐related inhibition of this response.
In conscious rats, cromakalim, 0.075 mg kg−1 i.v., produced a rapid and sustained fall in arterial blood pressure which was not influenced by pretreatment (2 h) with a large oral dose of glibenclamide (100 mg kg−1).
In conscious rats, the hypotensive action of cromakalim, 0.075 mg kg−1 i.v., was abolished by pretreatment (30 min) with glibenclamide, 20 mg kg−1, given by the intravenous route.
The results suggest that the vasorelaxant and hypotensive actions of cromakalim involve a K+ channel which can be inhibited by glibenclamide, but which may be distinct from the ATP‐sensitive K+ channel of the pancreatic β‐cell.
6‐Cyano‐7‐nitroquinoxaline‐2,3‐dione as an excitatory amino acid antagonist in area CA1 of rat hippocampus
Authors: Blake J.F. , Yates R.G. , Brown M.W. , Collingridge G.L. 
Published: July 2012

A quantitative pharmacological investigation of the excitatory amino acid antagonist 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) has been made in area CA1 of rat hippocampal slices bathed in 1 mm Mg2+ containing medium.
At a concentration of 10 μm, CNQX reversibly antagonized responses to α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA), quisqualate and kainate; it produced a parallel shift in their log dose‐response curves. Responses to N‐methyl‐d‐aspartate (NMDA) were not antagonized by 10 μm CNQX (dose‐ratio: 1.04 ± 0.06, n = 3).
Schild plots (constructed over the range 1–100 μm) yielded the following estimated pA2 values, AMPA 5.8, quisqualate 5.9, and kainate 5.9. NMDA was antagonized by 100 μm CNQX, giving an apparent log K of 4.44 ± 0.06.
The slopes (±s.e.mean) of the Schild plots were for AMPA 0.84 + 0.06, quisqualate 0.79 ± 0.04 and kainate 0.68 ± 0.07. These were all significantly less than unity.
Synaptic responses elicited by low frequency activation of the Schaffer collateral‐commissural pathway were blocked completely by CNQX (10 μm) providing that a low stimulus intensity was used. With high intensity stimulation a small component remained that was blocked by the selective NMDA antagonist d‐2‐amino‐5‐phosphonovalerate (APV).
These results suggest that CNQX does not differentially affect the responses of CA1 neurones to AMPA, quisqualate and kainate. It does, however, depress responses to these agonists to a greater degree than it does responses to NMDA and it is a highly effective synaptic antagonist.
Sex‐related differences in central adrenergic function and responsiveness to repeated administration of desipramine or electroconvulsive shock
Authors: Heal D.J. , Bristow L.M. , Hurst E.M. , Elliott J.M. , Buckett W.R. 
Published: July 2012

Clonidine induces hypoactivity in rodents. Male rats were found to be markedly more susceptible to the sedative effects of this α2‐adrenoceptor agonist than females. Thus to obtain identical hypoactivity responses for subsequent experiments, clonidine was administered to male and female rats at doses of 0.2 and 0.5 mg kg−1, respectively.
The clonidine‐induced hypoactivity response of female rats was not affected by the oestrous cycle.
Repeated injection of desipramine (DMI; 5 mg kg−1 b.d.) for up to 14 days progressively attenuated clonidine‐induced hypoactivity in both male and female rats. However, in males the attenuation was more rapid in onset and a greater overall reduction was obtained. This α2‐adrenoceptor‐mediated response was also progressively reversed by repeated daily administration of an electroconvulsive shock (ECS; 110 V, 1 s). In this case, although the maximum decrease was greater in males, the time of onset was identical in both sexes.
There were no sex‐related differences in either the number or affinity of α2‐ and β‐adrenoceptors in rat cortex. Cortical α2‐adrenoceptors were decreased by 14 days of DMI injection or 10 days of ECS treatment (ECS × 10) and these effects were identical in both sexes. These receptors were not altered by 2 days administration of DMI or ECS. Cortical β‐adrenoceptors were reduced in male and female rats by 2 and 14 days of DMI injection and by ECS × 10, but not ECS × 2.
Viewed overall, the data show differences in α2‐adrenoceptor function between the sexes, as determined by clonidine‐induced hypoactivity and the responsiveness of this paradigm to repeated administration of DMI and ECS. In contrast, no differences were observed in complementary α2‐ and β‐adrenoceptor binding experiments using rat cortical tissue.
Further characterization of the 5‐HT receptor mediating vascular relaxation and elevation of cyclic AMP in porcine isolated vena cava
Authors: Sumner M.J. , Feniuk W. , Humphrey P.P.A. 
Published: July 2012

5‐Hydroxytryptamine (5‐HT) and 5‐carboxamidotryptamine (5‐CT) produce both smooth muscle relaxation and elevation of tissue adenosine 3′: 5′‐cyclic monophosphate (cyclic AMP) levels in isolated rings of neonatal porcine vena cava. We now present studies attempting to characterize in more detail the 5‐HT receptor mediating these responses.
Both 5‐HT and 5‐CT relaxed porcine isolated vena cava rings (EC50 values 200 nm and 4 nm respectively) and elevated tissue cyclic AMP levels (EC50 values 1500 nm and 16 nm respectively). For both responses 5‐CT was approximately 50–100 fold more potent than 5‐HT.
Both 5‐CT‐induced smooth muscle relaxation and cyclic AMP elevation were potently and specifically antagonized to a similar extent by methiothepin, methysergide and spiperone.
At concentrations up to 1 μm, 8‐hydroxy‐2‐(di‐n‐propylamino) tetralin, buspirone, ipsapirone, n,n‐dipropyl‐5‐CT, cyanopindolol, RU24969, ketanserin, GR38032 and GR43175 were devoid of both agonist and antagonist activity for both responses.
These findings suggest that the same 5‐HT1‐like receptor mediates both smooth muscle relaxation and elevation of cyclic AMP. This receptor is unlike any known 5‐HT1 ligand binding site or adenylate cyclase‐coupled 5‐HT receptor in brain tissues.
Involvement of the protein kinase C system in calcium‐force relationships in ferret aorta
Authors: Ruzycky A.L. , Morgan Kathleen G. 
Published: July 2012

Intracellular Ca2+‐force relationships were investigated in ferret aortic smooth muscle by the simultaneous measurement of aequorin luminescence and isometric force. Complete calcium‐force curves were constructed by plotting calibrated aequorin luminescence versus force, while intracellular [Ca2+] was made to change by increasing degrees of K+ depolarization or decreasing extracellular [Ca2+].
The steady state calcium‐force curve in response to K+ depolarization exhibited maximal force generation at an intracellular [Ca2+] of approximately 4 × 10−7 m. Further increases in intracellular [Ca2+] did not yield additional increments in force.
Protein kinase C activation with the phorbol ester, 12‐deoxyphorbol‐13‐isobutyrate 20 acetate (DPBA) produced contractions accompanied by no detectable increases in aequorin luminescence. DPBA significantly shifted the control [Ca2+]‐force relationship leftward to lower intracellular [Ca2+] with an increase in the magnitude of maximal generated force.
In aorta maximally precontracted by K+ depolarization, the addition of DPBA resulted in a significant increase in force in the absence of further increases in intracellular [Ca2+]. Conversely, in muscles maximally precontracted with DPBA, responses to K+ depolarization resulted in subsequent increases in force in the presence of simultaneous sustained increases in intracellular [Ca2+].
The relatively specific protein kinase C antagonist H‐7 caused a significant decrease in intrinsic myogenic tone in the absence of any statistically significant decrease in intracellular [Ca2+].
These results suggest that protein kinase C may be an important regulator of vascular smooth muscle contractility by: (1) providing a mechanism by which the apparent [Ca2+] sensitivity of the contractile apparatus during agonist‐induced contractions is increased, and (2) maintaining intrinsic myogenic tone by a mechanism the [Ca2+] requirement of which is satisfied by the resting [Ca2+]i.
Secretion of acetylcholinesterase and butyrylcholinesterase from the guinea‐pig isolated ileum
Authors: Appleyard M.E. , Smith A.D. 
Published: July 2012

Strips of longitudinal muscle from guinea‐pig ileum, retaining Auerbach's plexus, were superfused with oxygenated Krebs solution. Addition of 50 mm KCl led to a pronounced Ca2+‐dependent increase in the activities of both acetylcholinesterase and non‐specific cholinesterase (butyrylcholinesterase) in the perfusate but with no change in lactate dehydrogenase activity.
No release of acetylcholinesterase, either spontaneous or K+‐evoked was observed in tissue freed of the nerve plexus, although release of butyrylcholinesterase still occurred.
Carbachol induced a marked Ca2+‐dependent increase in the release of acetylcholinesterase but had no effect on the release of butyrylcholinesterase or lactate dehydrogenase. This carbachol‐evoked increase in acetylcholinesterase release was blocked by hexamethonium but not by atropine.
Four readily soluble molecular forms of acetylcholinesterase and three soluble molecular forms of butyrylcholinesterase were present in innervated longitudinal muscle strips, but insignificant amounts of acetylcholinesterase were detected in denervated strips of muscle. Only one of the four molecular forms of acetylcholinesterase was recovered in the perfusates.
It is concluded that acetylcholinesterase is secreted from the nerves of Auerbach's plexus in response to depolarizing stimuli or to nicotinic cholinergic stimulation, while butyrylcholinesterase is secreted from non‐neural elements, possibly the longitudinal muscle cells, of guinea‐pig ileum in response to a depolarizing stimulus.
Effect of pirenzepine and gallamine on cardiac and pulmonary muscarinic receptors in the rabbit
Authors: Maclagan Jennifer , Faulkner David 
Published: July 2012

The effect of muscarinic antagonists considered to be selective for M1 receptors (pirenzepine) and for M2 receptors (gallamine) were studied on bronchoconstriction and bradycardia elicited by stimulation of the vagal nerves and by i.v. acetylcholine (ACh) in anaesthetized rabbits.
Pirenzepine was equipotent as an antagonist of ACh‐induced responses at postjunctional muscarinic receptors in the heart, lung and blood vessels, whereas gallamine was at least ten times less potent at pulmonary and vascular muscarinic receptors. Thus, gallamine never caused complete inhibition of bronchoconstrictor or hypotensive responses to i.v. ACh, whereas doses of pirenzepine in excess of 1 μmol kg−1 abolished all muscarinic responses.
In the lung, both antagonists inhibited bronchoconstriction caused by vagal stimulation and ACh‐induced bronchoconstriction to the same extent (pirenzepine, mean ED50 65 ± 22 and 130 ± 28 nmol kg−1 respectively; gallamine, ED50 > 10,000 nmol kg−1 for both responses). Enhancement of vagally‐induced bronchoconstriction was never observed.
In the heart, however, both pirenzepine and gallamine were ten times less potent as antagonists of vagally‐induced bradycardia than of ACh‐induced bradycardia. This differential blockade was unaltered by propranolol (1 mg kg−1) pretreatment.
It is concluded that there is no evidence for M1 or M2 muscarinic receptors in the pulmonary innervation of the rabbit and the potency of the antagonists in abolishing vagally‐induced bronchoconstriction was consistent with blockade of M3 muscarinic receptors on airway smooth muscle.
The results suggest that M2 muscarinic receptors may exert an inhibitory effect on transmission in the parasympathetic nerves innervating the heart in the rabbit. Blockade of such neuronal receptors would increase transmitter output to the atrial cells and explain the low potency of both antagonists in abolishing vagally‐induced bradycardia in the rabbit.
Generation of histamine‐releasing activity from serum albumin by medium derived from stimulated neutrophils of rat
Authors: Cochrane David E. , Boucher William , Carraway Robert E. 
Published: July 2012

Medium conditioned by rat neutrophils stimulated by N‐formyl‐methionyl‐leucyl‐phenylalanine (FMLP) has been found to generate mast cell histamine‐releasing activity (HRA) when incubated with bovine serum albumin (BSA).
Histamine release increased as the concentration of BSA used to generate HRA was increased from 0.25 to 10 mg ml−1, as the concentration of neurotrophil conditioned medium was increased and as the concentration of FMLP used to stimulate the neutrophils was increased. Histamine release was non‐cytotoxic as it was inhibited by energy deprivation or by removal of calcium and it was accompanied by degranulation.
HRA was detectable after 30 min of incubation with BSA and its generation continued to increase over the 18 h of our measurements.
Generation of HRA was dependent upon the presence of medium from stimulated neutrophils and on the presence of BSA, although plasma could substitute for BSA. Likewise, HRA could be generated from γ‐globulin although to a lesser extent than with albumin.
Generation was optimum at acid pH and was inhibited by prior boiling of the neutrophil conditioned medium or by the addition of pepstatin.
It is suggested that an enzyme(s) released from the neutrophil during stimulation acts on an albumin‐like substrate to generate HRA. It is proposed that HRA is peptide in nature and may be generated during an inflammatory response.
Inhibition of histamine‐stimulated inositol phospholipid hydrolysis by agents which increase cyclic AMP levels in bovine tracheal smooth muscle
Authors: Hall I.P. , Donaldsona J. , Hill S.J. 
Published: July 2012

The effect on histamine‐stimulated [3H]‐inositol phosphate accumulation of a range of agents which increase the accumulation, or mimic the actions, of cyclic AMP has been investigated in bovine tracheal smooth muscle.
Salbutamol (1 μm), forskolin (1 μm) and vasoactive intestinal peptide (VIP, 1 μm) inhibited the inositol phosphate response to 0.1 mm histamine and increased the accumulation of [3H]‐cyclic AMP in [3H]‐adenine‐labelled slices of bovine tracheal smooth muscle. The effect on inositol phospholipid hydrolysis was mimicked by the membrane permeant analogues of cyclic AMP, dibutryl‐cyclic AMP (1 mm) and 8‐bromo‐cyclic AMP (1 mm).
In contrast to salbutamol, which was equally effective at producing the two effects, forskolin produced large increases in [3H]‐cyclic AMP accumulation (EC50 = 1.2 μm) at much higher concentrations than those required for inhibition of histamine‐stimulated [3H]‐inositol phosphate accumulation (EC50 = 0.09 μm). However, significant increases in [3H]‐cyclic AMP accumulation, of similar magnitude to those obtained with salbutamol and VIP, were observed over the concentration range appropriate for inhibition of the inositol phosphate response to histamine.
In the presence of histamine (0.1 mm), isobutylmethylxanthine (IBMX, 1 mm) and rolipram (0.1 mm) both significantly (P < 0.05) elevated tissue [3H]‐cyclic AMP levels. IBMX, rolipram and (to a lesser extent) SKF 94120 significantly (P < 0.05) reduced histamine‐stimulated [3H]‐inositol phosphate accumulation by 81%, 68% and 20%, respectively. M&B 22948 was without a significant effect on either [3H]‐cyclic AMP or histamine‐induced [3H]‐inositol phosphate accumulation.
Both rolipram and forskolin reduced the increase in incorporation of [3H]‐inositol into membrane phospholipids which followed stimulation with histamine. However, a significant inhibition of [3H]‐inositol phosphate accumulation could be demonstrated under conditions in which there was no change in the level of [3H]‐inositol incorporation.
Alterations of coronary vascular responses to noradrenaline, acetylcholine and isoprenaline during acute myocardinal ischaemia in dogs
Authors: Sun Jian‐Zhong , Li Zhi‐Yuan , Zang Yi‐Min , Wang Fu‐Zhou 
Published: July 2012

The reactivity of coronary arteries to noradrenaline (NA), acetylcholine (ACh) and isoprenaline (Iso) during acute myocardial ischaemia was studied in anaesthetized, open‐chest dogs.
The left anterior descending coronary artery (LAD) was cannulated and perfused via an extracorporal circuit at constant flow. Ischaemia was produced by decreasing the perfusion blood flow of the LAD to 50% (moderate ischaemia) and 27% (severe ischemia) of normal. A dose of each agent which had no significant myocardial effects was chosen. Heart rate was held constant by ventricular pacing during ACh administration.
Under normal conditions, the infusion of NA, ACh and Iso into the LAD produced significant decreases in coronary vascular resistance (P < 0.01). However, under either moderate or severe ischaemic conditions intracoronary NA resulted in a marked increase in coronary vascular resistance (P < 0.01), which was completely blocked by phentolamine, an α‐adrenoceptor blocker; intracoronary ACh and Iso did not have a significant effect on coronary vascular resistance (P > 0.05).
These results indicate that coronary arterial responsiveness to some intrinsic vasoactive substances, such as NA and ACh, is altered during acute myocardial ischaemia. This may be important in the pathophysiology of myocardial ischaemia.
The action of dopamine and vascular dopamine (DA1) receptor agonists on human isolated subcutaneous and omental small arteries
Authors: Hughes A.D. , Sever P.S. 
Published: July 2012

Human small arteries were obtained from surgical specimens and studied in vitro by use of a myograph technique. Following induction of tone with a potassium depolarizing solution, dopamine in the presence of β‐adrenoceptor and catecholamine uptake blockade relaxed isolated omental and subcutaneous arteries. Preincubation of tissues with phentolamine increased the maximum relaxation in response to dopamine.
The selective vascular dopamine receptor agonists, fenoldopam and SKF 38393 also relaxed isolated subcutaneous and omental arteries in a concentration‐dependent manner. The order of potency for agonists was dopamine > fenoldopam > SKF 38393.
Dopamine‐induced relaxation was competitively antagonized by SCH 23390, (R)− and (S)‐sulpiride, and fenoldopam induced relaxation by SCH 23390 and (+)− but not (−)‐butaclamol.
These results indicate the presence of vascular dopamine receptors (DA1 subtype) on human isolated resistance arteries from omental and subcutaneous sites.