bluuebunny/crossref_metadata_2025_split huggingface dataset:
Forskolin, cyclic nucleotides and positive inotropism in isolated papillary muscles of the rabbit
Authors: Rodger I.W. , Shahid M. 
Published: July 2012

The effects of forskolin, isoprenaline, sodium nitroprusside and the frequency of stimulation were examined on cyclic nucleotide levels and tension responses in rabbit isolated right ventricular papillary muscles.
Increasing the frequency of stimulation from 0.01 Hz to 1.6 Hz induced positive inotropic responses that were not obviously related to alterations in the level of either cyclic AMP or cyclic GMP.
Isoprenaline induced rapid, concentration‐related positive inotropic responses that were associated with increases in the levels of both cyclic AMP and cyclic GMP. There existed good correlations between the increases in tension and the concentrations of both cyclic nucleotides measured in the tissues.
Forskolin induced concentration‐related positive inotropic responses that were slow to develop. These responses were accompanied by concentration‐related increases in the levels of cyclic AMP but not cyclic GMP. The tension responses correlated well with the levels of cyclic AMP measured. The cyclic AMP levels produced by forskolin were some 8 fold higher than those induced by isoprenaline for similar increases in tension.
Sodium nitroprusside was without inotropic effect either positive or negative; it nevertheless elevated cyclic GMP levels whilst slightly reducing cyclic AMP levels.
These data show that the ratio of cyclic AMP to cyclic GMP does not correlate well with changes in mammalian cardiac contractility. The data further suggest that whilst the intracellular concentration of cyclic AMP in rabbit ventricular myocardium may be an important determinant of positive inotropism, the relationship between the two parameters is more complex than simple proportionality between the tension generated and the amount of cyclic AMP measured within the cells.
Excitant activity of methyl derivatives of quinolinic acid on rat cortical neurones
Authors: Stone Trevor W. 
Published: July 2012

Various synthetic analogues of quinolinic acid have been tested for agonist and antagonist properties when applied by microiontophoresis to neurones in the rat cerebral cortex.
Quinolinic acid 2‐methylester was a weak antagonist of N‐methyl‐d‐aspartate (NMDA) and quinolinic acid, but also showed agonist activity, being about half as active as quinolinic acid. The excitant effects of the compound could be antagonized by the NMDA receptor blocker, 2‐amino‐7‐phosphonoheptanoic acid (2APH). N‐methyl‐quinolinic acid 2,3‐dimethylester showed very weak agonist and antagonist activity.
Homoquinolinic acid was a potent excitant of cortical neurones, being about five times more active than quinolinic acid and approximately equipotent with NMDA. The excitations were blocked by 2APH or its pentanoate analogue (2APV). Homoquinolinic acid 2‐methylester was also active as an agonist.
N‐methyl‐dl‐glutamic acid was also tested, since homoquinolinic acid is a rigid analogue of this compound. Although it did cause excitation of 5 of the 16 units tested, N‐methyl‐glutamate was a weaker agonist than NMDA or homoquinolinate.
Phthallic acid, ejected as an anion caused excitation of 14 out of 16 units. It is therefore concluded that the ring nitrogen of quinolinic acid is not essential for excitant activity.
Since homoquinolinic acid is a rigid analogue of glutamic acid, but causes excitation by acting apparently on the NMDA receptor, the results are consistent with the suggestion that activation of the NMDA receptor may require the carboxyl groups to be held in a relatively extended configuration.
The effects of 3,5,5‐trimethylcyclohexanol on hepatic cholesterol synthesis, bile flow and biliary lipid secretion in the rat
Authors: Bell G.D. , Clegg R.J. , Ellis W.R. , Middleton B. , White D.A. 
Published: July 2012

The chemical trimethylcyclohexanol (TMC) is closely related to menthol, the major component of a terpene preparation with known choleretic and cholelitholytic activity. Its effects on hepatic cholesterol synthesis and bile secretion were examined in the rat.
In both acute and long‐term dosing experiments TMC significantly inhibited hepatic S‐3‐hydroxy‐3‐methylglutaryl coenzyme A (HMGCoA) reductase. TMC was a potent choleretic, with detectable effects on bile flow at low doses, which also reduced coupling of cholesterol secretion to bile salt secretion. Single large doses tended to lower biliary cholesterol output and caused significant reduction in cholesterol saturation index after biliary diversion for 1h.
TMC and its widely prescribed ester cyclandelate, which is rapidly degraded to TMC after ingestion, should be investigated further as potential cholelitholytic treatments in man.
The platelet‐independent release of thromboxane A2 by Paf‐acether from guinea‐pig lungs involves mechanisms distinct from those for leukotriene
Authors: Lefort J. , Rotilio D. , Vargaftig B.B. 
Published: July 2012

Intra‐arterial injections of platelet‐activating factor (Paf‐acether, 10–300 ng) to the perfused guinea‐pig lung induced a dose‐related bronchoconstriction, followed by contraction of the rat aorta superfused with the lung effluent, indicating the release of thromboxane A2 (TXA2) activity. These effects were matched with injections of bradykinin (Bk) at 100–1000 ng, leukotriene C4 (LTC4) at 10–300 ng or arachidonic acid (AA) at 30–300 μg.
Repeated doses of Paf‐acether led to a specific desensitization of the release of TXA2, under conditions where Bk, LTC4 and arachidonic acid retained their ability to release TXA2.
Bronchoconstriction and the release of TXA2 induced by Paf‐acether were suppressed when the lungs were perfused with acetylsalicylic acid, but not with salicylic acid.
The phospholipase A2 inhibitor, p‐bromophenacyl bromide suppressed the release of TXA2 by Bk, but did not interfere with its formation from AA, nor with its release with Paf‐acether and LTC4. The lipoxygenase inhibitor, nordihydroguaiaretic acid, inhibited to a similar extent the release of TXA2 by Bk, LTC4 and Paf‐acether but also reduced directly the formation of TXA2 from arachidonic acid, invalidating its use as a specific antilipoxygenase agent.
The leukotriene C4/D4 antagonist, FPL 55712, suppressed the TXA2 releasing effects of LTC4, and was completely inactive against Paf‐acether, Bk or arachidonic acid.
The aerosol of Paf‐acether was tested in the anaesthetized guinea‐pig and resulted in bronchoconstriction, unaccompanied by thrombocytopenia. Unlike bronchoconstriction induced by intravenous Paf‐acether, which is refractory to cyclo‐oxygenase inhibitors, the effects of the aerosol were suppressed by aspirin. Platelet depletion, which blocks the intravenous effects of Paf‐acether, failed to interfere with those of the aerosol.
Paf‐acether induced a marked contraction of the superfused guinea‐pig isolated parenchyma lung strip, which was followed by total and irreversible desensitization to itself. The contractile effect was not inhibited by aspirin or indomethacin, atropine, mepyramine, methysergide, phenoxybenzamine or propranolol, indicating that cyclo‐oxygenase products, cholinergic stimuli, histamine, 5‐hydroxytryptamine and catecholamine mechanisms are not involved.
Our results indicate that Paf‐acether interacts with pulmonary sites distinct from those for Bk, LTC4 or AA, since no cross‐desensitization between Paf‐acether and the other agonists was noted, p‐bromophenacyl bromide inhibited Bk only and FPL 55712 inhibited only LTC4. The phospholipase A2 involved with the release of the arachidonate needed for the formation of TXA2 by Paf‐acether or LTC4‐stimulated lungs may differ from the enzyme accounting for its formation by Bk. The cellular sites with which Paf‐acether interacts may also be distinct and less readily accessible to p‐bromophenacyl bromide.
Role of calcium ions in kinin‐induced chloride secretion
Authors: Cuthbert A. W. , Halushka P.V. , Margolius H.S. , Spayne J. A. 
Published: July 2012

Electrogenic ion transport across the epithelium lining the descending colon of male Sprague‐Dawley rats has been measured under short‐circuit conditions.
Responses to kallidin (lysylbradykinin) were inhibited by 70% if calcium was removed from the solution bathing the basolateral aspect of the tissue. Under identical conditions responses to prostaglandin E1 and dibutyryl cyclic adenosine monophosphate were not changed. Forskolin, which directly activates the catalytic subunit of adenylate cyclase, was inhibited by 35% by calcium removal, whereas responses to the phosphodiesterase inhibitor isobutylmethylxanthine were inhibited by 45 % by the same procedure.
In the absence of calcium, strontium could substitute in promoting the chloride secretory events triggered by kallidin. Magnesium ions antagonized the effects of the kinin in the presence of calcium ions in the bathing solution.
The effects of kallidin were partially antagonized by verapamil and trifluoperazine and were potentiated by isobutylmethylxanthine.
These results, together with earlier evidence, suggest that kinin elicits a chloride secretory response in this epithelium by stimulating the formation of prostaglandins which then activate adenylate cyclase. Extracellular calcium ions appear to have an important role in the proximal part of this cascade for prostaglandin generation. However, biochemical correlates of these biophysical responses presented in the following paper indicate a more complex role for calcium in the genesis of the kinin response.
The channel‐blocking action of methonium compounds on rat submandibular ganglion cells
Authors: Gurney A.M. , Rang H.P. 
Published: July 2012

The effects of drugs of the polymethylene bis‐trimethylammonium (methonium) series on the characteristics of the synaptic currents (e.s.cs) recorded from voltage‐clamped rat submandibular ganglion cells have been studied. The drugs studied were from C4 to C10 (decamethonium).
All of the drugs except C4 shortened the initial decay phase of the e.s.c.; C9 and C10 produced an additional slowly decaying component. These effects were interpreted in terms of an open channel block mechanism, the calculated rate constants for association with the open channel at — 80 mV being fairly similar (5.9 × 106 to 18.1 × 106m−1 s−1) for all of the compounds except C4, which had no effect on the e.s.c. decay.
All of the compounds produced use‐dependent block when tested with short trains of stimuli at 10 Hz, or with trains of ionophoretic pulses of acetylcholine, consistent with their channel blocking property. Tubocurarine had a similar effect, but not trimetaphan or mecamylamine.
Recovery from use‐dependent block with short chain methonium compounds, up to C8, was very slow in the absence of agonist, being incomplete even after several minutes. With C9 or C10 or tubocurarine, recovery from use‐dependent block was complete within a few seconds. With C6 recovery in the absence of agonist was unaffected by membrane potential, but could be accelerated by applying acetylcholine with the cell depolarized to — 40 mV. This persistent block was ascribed to the ability of the blocking molecule to become trapped by closure of the channel. With C9 and C10 it is assumed that their presence inhibits channel closure, so they can escape without the help of agonist.
When use‐dependent block is avoided by leaving the ganglion unstimulated during equilibration with the blocking drug, the first e.s.c. elicited shows no appreciable reduction of amplitude, though with C6, C7 or C8 subsequent responses elicited at 0.1 Hz become progressively more blocked.
Even at 1 mm, C6 does not prevent acetylcholine from opening ionic channels.
It is concluded that all of the effects on e.s.c. amplitude can be interpreted in terms of channel block, there being no evidence of any receptor blocking action.
Classification of β‐adrenoceptors in human isolated bronchus
Authors: Goldie Roy G. , Paterson James W. , Spina Domenico , Wale Janet L. 
Published: July 2012

(±)‐Isoprenaline (Iso), (−)−adrenaline (Ad), (−)−noradrenaline (NA), (±)‐phenylephrine (Phe) and the β2‐selective adrenoceptor agonist (±)‐fenoterol (Fen) caused a concentration‐dependent relaxation of human isolated bronchial preparations. Iso, Ad and NA caused complete relaxation of both spontaneous and carbachol‐induced bronchial tone. Fen, which was only tested in preparations where tone was induced with carbachol, also caused complete relaxation. However, Phe was a partial agonist in all preparations tested.
When relaxation responses to these amines were calculated as a % of their maximal effects, comparison of EC50 values showed that the order of potency was Iso > Ad = Fen > NA > Phe (92:27:25:1:0.2) in preparations with carbachol‐induced tone and Iso > Ad > NA > Phe (112:38:1:0.3) in preparations with spontaneous tone.
pA2 values determined for the β‐adrenoceptor antagonists propranolol (non‐selective), atenolol (β‐selective) and ICI‐118, 551 (β2‐selective), using Iso as an agonist were, 9.3, 5.3 and 9.1 respectively.
These results indicate that β2‐adrenoceptors mediate relaxation of human isolated bronchus to sympathomimetic amines in preparations obtained 4–14 h post‐mortem from non‐diseased lung. α‐Adrenoceptors were apparently sparse or absent in this tissue.
Modification by betamethasone of the effects of bronchodilator drugs on cholinergic bronchoconstriction in rats
Authors: Mattila M.J. , Salonen R.O. 
Published: July 2012

Effects of betamethasone (BM), a long‐acting glucocorticoid, given alone and in combination with bronchodilator drugs, terbutaline (Ter), theophylline (Theo), or ipratropium bromide (Ipra), were studied on dose‐related methacholine (MeCh 2, 3, and 4.5 μg i.v.)‐induced bronchoconstriction in anaesthetized rats. BM (0.4 or 2 mg kg−1) was given intraperitoneally 24 h before the experiment followed by a similar dose intravenously, 12 min before MeCh challenge. The bronchodilator drugs were given i.v. as acute single doses.
BM 0.4 mg kg−1 counteracted significantly MeCh‐induced bronchoconstriction without modifying MeCh‐induced transient bradycardia and hypotension. BM 2 mg kg−1 failed to improve that response. A time interval of 24 h after pre treatment proved mandatory to produce these effects.
Combined treatment with BM 0.4 mg kg−1 + Ter 20 μg kg−1 antagonized the MeCh‐induced bronchoconstriction in an additive manner at 2 and 3 μg of MeCh, but a synergistic interaction was found at the largest MeCh dose. The effects of the other combinations (BM 0.4 mg kg−1 + Theo 20 mg kg−1 and BM 0.4 mg kg−1 + Ipra 0.5 μg kg−1) on airways failed to exceed the expected sum of the individual drugs.
The combination of BM + Ter was selective to the airways only, whereas BM + Theo also counteracted MeCh‐induced bradycardia and BM + Ipra counteracted both hypotension and bradycardia.
It is concluded that combined treatment with glucocorticoid and β2‐adrenoceptor agonist may result in a synergistic interaction on severe airway obstruction without significant influence on cardiovascular system.
The antidyskinetic action of dihomo‐γ‐linolenic acid in the rodent
Authors: Costall Brenda , Kelly M. Elizabeth , Naylor R.J. 
Published: July 2012

The antidyskinetic action of dihomo‐γ‐linolenic acid (DHLA) was assessed against dyskinesias induced in the guinea‐pig by dopamine injected into the striatum (200 μg bilateral 2 h after nialamide, 75 mg kg−1, i.p.) and in the guinea‐pig and rat by 2‐di‐n‐propylamino‐5, 6‐dihydroxytetralin (tetraiin), 0.025 mg kg−1, s.c.
Dopamine and tetralin‐induced dyskinesias in the guinea‐pig were reduced or abolished by DHLA given i.p., 30−100 mg kg−1, given once daily for 5–10 days.
Tetralin‐induced dyskinesias were antagonized by DHLA given orally to the guinea‐pig (50−200 mg kg−1, 5 days) or in the diet to the rat (approximately 200 mg kg−1 daily for 10−14 days).
DHLA injected into the striatum (2.5−20 μg bilateral, 2–4 days) also antagonized tetralin‐induced dyskinesias in the rat.
The antidyskinetic action of DHLA given i.p. to the guinea‐pig could be antagonized by aspirin or eicosa‐5,8,11,14‐tetraynoic acid (100 mg kg−1 i.p. daily, starting 2 days before a 5 day treatment with DHLA). Aspirin (25−100 mg kg−1, i.p.) dose‐dependently antagonized the antidyskinetic activity of 5 and 20 μg DHLA given bilaterally into the striatum (2 days).
DHLA (100 mg kg−1 i.p.) given daily for 10 days or approximately 200 mg kg−1 DHLA (daily for 10–14 days given in the diet) administration to the rat failed to modify the stereotyped behaviour induced by apomorphine, 0.5 or 2 mg kg−1 s.c., to induce catalepsy, or to modify the cataleptic effects of haloperidol 0.25 or 1 mg kg−1 i.p.
It is suggested that the selective inhibition of dyskinesias in the rodent by DHLA may reflect a striatal effect with a dependency on conversion to prostaglandins.
The molal volumes of atropine and hyoscine in relation to their respective potencies
Authors: Cohen Sasson , Haberman Frank 
Published: July 2012

The partial molal volumes, , at infinite dilution of atropine and hyoscine were determined in each of eight different solvents having cohesive energy densities in the range 64 to 144 cal cm−3.
for hyoscine in a given solvent was invariably and significantly smaller than that of atropine in the same solvent. The difference being 1.58 cm3 mol−1 in the least polar solvent (n‐propylbenzene) and 4.29 cm3 mol−1 in the most polar one (acetonitrile) in the series studied.
It is proposed that the lower affinity of atropine relative to that of hyoscine for the muscarinic cholinoceptor could be accounted for by the relative increase in enthalpy in the adsorption of atropine to the receptor with respect to the same process with hyoscine.
Presynaptic, muscarinic inhibition of non‐adrenergic, non‐cholinergic neuromuscular transmission in the chicken rectum
Authors: Komori S. , Ohashi H. 
Published: July 2012

Cholinergic inhibition of the non‐adrenergic, non‐cholinergic (NANC) transmission was investigated in the chicken isolated rectum with Remak's nerve attached.
Stimulation of Remak's nerve (RT stimulation) at frequencies higher than 5 Hz elicited a late, slow contraction of the rectum in addition to an initial, fast NANC contraction. The late, slow contraction was blocked by atropine (0.25 μg ml−1), potentiated by physostigmine (50 ng ml−1) and accompanied by an overflow of acetylcholine into the vascular perfusate, indicating the existence of cholinergic innervation to the rectum via Remak's nerve.
RT stimulation (10 pulses at 0.5–1.0 Hz) elicited NANC‐mediated excitatory junction potentials (e.j.ps). The e.j.p. amplitude declined at the second stimulus and then increased to reach a plateau. Atropine, by abolishing this decrease in amplitude, increased the mean amplitude of the e.j.ps during trains of stimuli but atropine did not affect the amplitude of the first e.j.p. Physostigmine reduced the mean e.j.p. amplitude, and this action was readily antagonized by atropine.
A single intramural nerve stimulation delivered 2 s or less before RT stimulation with trains of stimuli, suppressed the amplitude of the first e.j.p. of the train. This effect was abolished by atropine.
Atropine in concentrations high enough to affect the e.j.p. amplitude had no effect on the resting membrane potential, the threshold for generating an action potential, or membrane resistance of the smooth muscle.
It is concluded that RT stimulation at low frequencies causes the release of acetylcholine simultaneously with the NANC transmitter. The released acetylcholine acts mainly on prejunctional muscarinic receptors and mediates an inhibitory effect on the release of the NANC transmitter.
Orthograde and retrograde axonal transport of calmodulin in a cat noradrenergic neurone
Authors: Ceña V. , Garcia A.G. , Gonzalez‐Garcia C. , Kirpekar S.M. 
Published: July 2012

Subcellular distribution studies of calmodulin in cat sympathetic ganglia demonstrated that about 90% of the protein remained in the 27,000 g supernatant, suggesting that it is a cytosolic protein. Only 4.5% was recovered in the microsomal fraction pellet.
The inferior mesenteric ganglia contained 93.3 ± 3 ng calmodulin per ganglion, and segments of unligated cat hypogastric nerves had 6.53 ± 0.32 ng per 5 mm segment.
When the nerve was ligated in the middle and left in the cat for 1–6 days, substantial amounts of calmodulin accumulated in segments of nerve immediately proximal (P1) and distal (D1) to the ligature. The amounts found in P1 amounted to 15.3, 20, 30.4 and 39.4 ng calmodulin per 5 mm segment 1, 2, 3 and 6 days after ligation, respectively. The average rate of transport was 5.5 mm per day, which corresponds to a slow component b of axonal transport (SCb).
The accumulation of calmodulin in D1 was also increased with the time of ligation. After 1, 2, 3 and 6 days, the amounts of the protein found in D1 were 14.4,17.7,19 and 21 ng per 5 mm segment, respectively. The calculated mean rate for the retrograde transport was 3.9 mm per day.
Decentralization of the inferior mesenteric ganglia did not affect the rate of accumulation of calmodulin or the basal amounts found in ganglia and nerves. Local injection inhibited the orthograde, but not the retrograde axonal transport of the protein.
It is concluded that calmodulin undergoes a process of slow orthograde axonal transport probably incorporated into the axoplasmic matrix of a network of actin microfilaments. The protein is also transported in a retrograde manner.
The calcium dependency of mucus glycoconjugate secretion by canine tracheal explants
Authors: Barbieri Edward J. , Bobyock Emil , Chernick Warren S. , McMichael Robert F. 
Published: July 2012

Canine tracheal explants, incubated overnight with [14C]‐glucosamine, elicited an enhanced secretion of ethanol‐precipitated 14C‐labelled glycoconjugate when challenged with methacholine, 10 μM.
Explants were rendered deficient in total calcium content and unresponsive to methacholine, 10 μM, by incubating them in calcium‐free medium for 18 to 22 h; however, the secretory response to the cholinergic agonist was restored with the addition of calcium to the medium.
A dose‐response relationship resulted when explants were challenged with methacholine in nutrient medium containing varied calcium concentrations (0.45 to 7.2 mM); alterations in the calcium concentration in the absence of methacholine had no significant effect on the basal secretion of 14C‐labelled glycoconjugate.
The calcium‐selective ionophore A23187, 10 μM, stimulated [14C]‐glycoconjugate secretion and induced the most significant effect in the presence of nutrient medium containing calcium.
Verapamil, 10 μM, a calcium‐entry blocker failed to inhibit basal or stimulated [14C]‐glycoconjugate secretion; however, the intracellular calcium antagonist TMB‐8, 10 to 100 μM, inhibited methacholine‐induced [14C]‐glycoconjugate secretion in a dose‐dependent manner.
These data suggest that respiratory mucus secretion is a calcium‐dependent process and that intracellular calcium is more vital than extracellular calcium in supporting this phenomenon.