bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE BINDING PROPERTIES OF THE MUSCARINIC RECEPTORS OF THE CYNOMOLGUS MONKEY CILIARY BODY AND THE RESPONSE TO THE INDUCTION OF AGONIST SUBSENSITIVITY
Authors: BÁRÁNY E. , BERRIE C.P. , BIRDSALL N.J.M. , BURGEN A.S.V. , HULME E.C. 
Published: July 2012

The binding properties of the muscarinic receptors in the ciliary muscle of cynomolgus monkeys have been evaluated.
The concentration of receptor binding sites is the highest yet reported. As found in many species and tissues, there are subclasses of agonist binding sites. Agonist binding is not affected by the non‐hydrolysable guanosine triphosphate (GTP) analogue, GppNHp, suggesting that these receptors are not linked to adenylate cyclase.
Ciliary muscles made subsensitive by treatment with muscarinic agonists have a decreased receptor concentration but no other changes in the binding properties of the receptors could be detected.
Studies on RX 781094: a selective, potent and specific antagonist of α2‐adrenoceptors
Authors: Doxey J.C. , Roach A.G. , Smith C.F.C. 
Published: July 2012

The selectivity and specificity of RX 781094 [2‐(2‐(1,4 benzodioxanyl))2‐imidazoline HCl] for α‐adrenoceptors have been examined in peripheral tissues.
In isolated tissue experiments RX 781094 was a competitive antagonist at prejunctional α2‐adrenoceptors situated on the sympathetic nerve terminals of the rat (pA2 = 8.56) and mouse (pA2 = 7.93) vas deferens and on the parasympathetic nerve terminals of the guinea‐pig ileum (pA2 = 8.55).
Although RX 781094 was also a competitive antagonist at the postjunctional α1‐adrenoceptors of the rat anococcygeus muscle (pA2 = 6.10) its affinity for these receptors was markedly less than that displayed for prejunctional sites. From pA2 values obtained in the rat vas deferens and anococcygeus muscle the calculated α2/α1‐adrenoceptor selectivity ratio for RX 781094 was 288.
The rank order of α2/α1‐adrenoceptor selectivities for the antagonists studied was RX 781094 > RS 21361 > yohimbine > piperoxan > phentolamine > WB 4101 > prazosin.
RX 781094 had extremely low affinity for β‐adrenoceptors, histamine receptors, cholinoceptors, 5‐hydroxytryptamine and opiate receptors in vitro.
In pithed rats, intravenous administration of RX 781094 antagonized the prejunctional α2‐adrenoceptor agonist effects of clonidine and guanabenz on electrically‐induced contractions of the vas deferens and anococcygeus muscle respectively.
In the vas deferens the rank order of α2‐adrenoceptor antagonist potencies was RX 781094 > phentolamine > piperoxan > yohimbine > RS 21361 > WB 4101. Only RX 781094, yohimbine and RS 21361 were active against guanabenz in the anococcygeus muscle.
In the pithed rat, RX 781094 preferentially antagonized the pressor responses evoked by postjunctional α2‐adrenoceptor activation by UK 14,304 although higher doses also inhibited the effects of phenylephrine and cirazoline at postjunctional α1‐adrenoceptors.
RX 781094 had little effect on the cardiovascular responses to 5‐hydroxytryptramine, angiotensin II, histamine, acetylcholine and isoprenaline in pithed rats and rats anaesthetized with pentobarbitone.
These results demonstrate that RX 781094 is a potent and selective α2‐adrenoceptor antagonist with a high degree of specificity for these receptors.
The evaluation of different types of anti‐convulsant drug activity against leptazol‐induced epileptogenic activity in the anaesthetized rat
Authors: Kent A.P. , Webster R.A. 
Published: July 2012

The effects of various anticonvulsant drugs were evaluated quantitatively on the development of the epileptogenic EEG, induced by the intravenous infusion of leptazol in rats anaesthetized with urethane.
Leptazol alone produced five distinct phases of EEG activity developing from early wave and small spike and wave activity to larger spikes which later grouped and led to full body convulsion (FBC).
Drugs effective in petit mal such as clonazepam (0.1 and 0.25 mg kg−1) and ethosuximide (100 and 200 mg kg−1), significantly delayed the time to FBC by prolonging the early phases of the epileptogenic EEG and delaying the appearance of spiking.
Drugs effective in grand mal such as sodium valproate (60 mg kg−1) and phenytoin (5 mg kg−1) significantly prolonged the time to FBC by extending the later phases of the EEG and the development and grouping of spikes. Higher doses of these compounds were without effect. Carbamazepine and phenobarbitone produced mixed effects but were generally not markedly anticonvulsant.
The model is sensitive to drugs effective in both petit mal and grand mal, and appears able to differentiate usefully between them.
Neuronal influence on the mechanical activity of the ciliary muscle
Authors: Suzuki Ryo 
Published: July 2012

Neuronal effects and the pharmacological properties of the bovine ciliary muscle were investigated in vitro. The bovine ciliary muscle exhibited no spontaneous activity.
Electrical stimulation of an isolated short ciliary nerve produced distinct contractions. The minimal stimulus duration required to evoke a contraction was 0.2 ms and amplitude of the contraction was maximal at 2 ms. Twitch or incomplete tetanus reached a complete tetanus with 4 Hz stimulation.
Raising the external potassium concentration from 5.9 to 158.8 mm produced a contracture which consisted of an initial phasic and then tonic components.
The contractions generated by either electrical stimulation (0.2–100 ms) or high K were potentiated by physostigmine and completely inhibited by atropine. Neither adrenoceptor agonists nor blockers influenced these contractions.
Application of tetraethylammonium (TEA), potentiated the electrically‐induced ciliary muscle contraction, and the effect of TEA was not completely inhibited by high concentrations of either atropine or tetrodotoxin. Thus, TEA presumably acts both pre‐junctionally and post‐junctionally to increase the contractile development of ciliary muscle.
The ciliary contractile response is primarily mediated by acetylcholine released from nerves, and this response is accompanied by a negligible contribution from the sympathetic nerves. Depolarization induced by electrical currents or by high K was ineffective in evoking contraction of the ciliary muscle.
The results suggest that excitation of the ciliary muscle is probably mediated via junction potentials or by a direct transmitter action without any very great change in the potential. Action potentials are probably generated in the presence of TEA.
Evidence against the temperature‐dependent interconversion of histamine H1‐ and H2‐receptors in the guinea‐pig ileum
Authors: Bertaccini G. , Zappia L. 
Published: July 2012

The possible temperature‐dependent interconversion of histamine H1‐ and H2‐receptors in the guinea‐pig ileum suggested from previous studies was re‐investigated by use of new and selective H2‐receptor agonists and antagonists.
Chlorpheniramine, an H1‐blocker, caused a rightward shift of the cumulative histamine dose‐response curve at both 37°C and 12°C. Conversely cimetidine and tiotidine, two H2‐receptor blockers, were ineffective at both temperatures. Metiamide behaved as a non competitive antagonist at 12°C but only in very high concentrations.
Dimaprit and impromidine, two selective H2‐receptor agonists, were inactive at both 37°C and 12°C when given alone, whereas at both temperatures they elicited the already described relaxation of the contractions induced by histamine.
Similar results were obtained on the guinea‐pig whole ileum and on the longitudinal muscle strip: this indicates a lack of interference of the circular smooth muscle.
Our results allow us to conclude that no temperature‐dependent interconversion of histamine H1‐ and H2‐receptors occurs in the guinea‐pig ileum.
Comparison of the effects of bicuculline and strychnine on brain stem auditory evoked potentials in the cat
Authors: Martin M.R. , Penix L.P. 
Published: July 2012

Experiments were performed to determine the effects of intravenously applied bicuculline and strychnine on the click‐evoked brain stem auditory evoked potentials (BAEP) of cats.
The BAEP was not affected by bicuculline (0.5 mg/kg, i.v.) administration. Strychnine (0.2 mg/kg, i.v.) administration caused a significant increase in the amplitude of peak 4, which is thought to be produced by potentials in the superior olive, lateral lemniscus and inferior colliculus.
These results suggest that strychnine blocks glycinergic inhibitory inputs to these auditory structures.
The effect of chronic antidepressant administration on β‐adrenoceptor function of the rat pineal
Authors: Cowen P.J. , Fraser Sheila , Grahame‐Smith D.G. , Green A.R. , Stanford Clare 
Published: July 2012

The β‐adrenoceptor agonist, isoprenaline (1.5–3.0 mg kg−1 intravenously), produced a dose‐related increase in rat pineal melatonin content. This increase was prevented by pretreatment with the selective β1‐adrenoceptor antagonist, atenolol (2 mg kg−1), but not by the β2‐adrenoceptor antagonist, butoxamine (2 mg kg−1). The β2‐adrenoceptor agonist, terbutaline (5.0 mg kg−1), produced a moderate increase in pineal melatonin content.
Repeated daily administration of desmethylimipramine (10 mg kg−1 for 10 days) and map‐rotiline (10 mg kg−1 for 10 days), antidepressants predominantly inhibiting noradrenaline (NA) uptake, reduced the isoprenaline‐induced increase in pineal melatonin content. Amitriptyline (20 mg kg−1 for 14 days), a drug which inhibits both NA and 5‐hydroxytryptamine (5‐HT) uptake, had a similar effect. The β‐adrenoceptor agonist, clenbuterol (5 mg kg−1 for 14 days), also attenuated the increase in pineal melatonin produced by isoprenaline.
In contrast, chronic administration of the selective 5‐HT uptake inhibitor, fluoxetine (10 mg kg−1 for 10 days), or the antidepressants, iprindole and mianserin (both 20 mg kg−1 for 14 days), which do not inhibit monoamine uptake, failed to reduce the increase in pineal melatonin following isoprenaline. Repeated electroconvulsive shock was similarly without effect.
Ten hours after the final dose of desmethylimipramine (10 mg kg−1) once daily for 10 days there was no change in the usual dark phase increase in pineal melatonin.
The data suggest that repeated administration of certain antidepressant drugs results in reduced pineal β‐adrenoceptor sensitivity. However the lack of change in the dark phase increase in pineal melatonin following repeated desmethylimipramine, implies that the reduced β‐adrenoceptor sensitivity may be part of an adaptive process which maintains normal pineal function. Therefore the decrease in β‐adrenoceptor number in the brain reported after chronic antidepressant administration may not be associated with a change in overall synaptic function.
Seasonal variations in drug response and staircase phenomena in atrial muscle from a hibernating rodent (Spermophilus richardsonii)
Authors: Charnock John S. , Dryden William F. , Marshall Richard J. 
Published: July 2012

Electrically driven atrial muscle from a hibernating rodent (Spermophilus richardsonii) showed marked seasonal variations in inotropic responsiveness to both the cardiac glycoside actodigin and to raised extracellular calcium concentration. In contrast, glycoside toxicity was apparent and comparable in all tissues.
These variations were accompanied by changes in force‐frequency (‘staircase’) characteristics of the tissues.
In contrast, no seasonal variation was observed in either positive inotropic responses to rubidium (a non‐glycoside inhibitor of Na+ + K+ ATP‐ase) or negative inotropic responses to methacholine.
In summer atria the calcium antagonist, verapamil (6 × 10−7 m) abolished the positive staircase phenomenon but did not modify the positive inotropic actions of actodigin.
These data do not support the hypothesis that ‘staircase’ and glycoside‐induced inotropism are mediated through a common mechanism.
An analysis of the effects of systemically administered clonidine on the food and water intake of rats
Authors: Sanger D.J. 
Published: July 2012

It is known that intracerebral injections of clonidine can induce eating in rats but it has not been clear whether systemic administration can produce similar effects.
Subcutaneous injections of clonidine (0.01, 0.03, 0.1 mg/kg) increased food and water intake during the 6 h period following injection in non‐deprived male rats.
Pretreatment with a dose of yohimbine (1.0 mg/kg) shifted the clonidine dose‐response curves to the right, suggesting competitive antagonism.
A dose of naloxone (0.1 mg/kg) produced a lowering of the clonidine dose‐response curve but statistical analysis suggested that the opiate antagonist did not produce a competitive antagonism of the effect of clonidine.
The results are consistent with a role for α2‐adrenoceptors in appetite regulation.
Stimulation and inhibition of prostacyclin formation in the gastric mucosa and ileum in vitro by anti‐inflammatory agents
Authors: Boughton‐Smith N.K. , Whittle B.J.R. 
Published: July 2012

Homogenates of rat gastric mucosa, forestomach and ileum and dog gastric mucosa reproducibly generated prostacyclin from endogenous substrate.
Prostacyclin formation was inhibited by pre‐incubation with indomethacin, flurbiprofen, naproxen, ketoprofen or meclofenamate (0.1–10 μm).
BW755C (3‐amino‐1[m‐(trifluoromethyl)‐phenyl]‐2‐pyrazoline) stimulated prostacyclin production in the rat gastric mucosa and ileum with inhibition occurring only at high concentrations (>200 μm). The stimulation of prostacyclin production by BW755C in rat forestomach homogenates was less pronounced, with inhibition at concentrations > 20 μm.
BW755C thus exhibits differential activity on prostacyclin production from different gastric tissues in vitro.
The antioxidant‐lipoxygenase inhibitor, nordihydroguiaretic acid (NDGA, 3–15 μm) likewise augmented rat mucosal prostacyclin formation.
Paracetamol stimulated and, at higher concentrations, inhibited prostacyclin formation (> 1 mm), and had comparable activity in both rat gastric tissues.
The ability of NDGA and BW755C to enhance prostacyclin generation may reflect the removal of a modulating influence of lipoxygenase products on prostacyclin formation, the diversion of substrate to the cyclo‐oxygenase pathway, or free‐radical scavenging.
Stimulation‐evoked release of [3H]‐noradrenaline by 1, 10 or 100 pulses and its modification through presynaptic α2‐adrenoceptors
Authors: Marshall Ian 
Published: July 2012

Mice isolated vasa deferentia were loaded with 1‐[7, 8‐3H]‐noradrenaline and subsequently field stimulated with 1, 10 or 100 pulses (2 ms pulse width, 1 Hz). The tritium overflow was separated into [3H]‐noradrenaline and its 3H‐metabolites.
The resting release of tritium contained about 7% [3H]‐noradrenaline, 33% [3H]‐3, 4‐dihydroxyphenylglycol ([3H]‐DOPEG) and 60% 3H‐non‐catechols with usually less than 1% [3H]‐dihydroxymandelic acid ([3H]‐DOMA). The proportion of the tritium as [3H]‐noradrenaline increased with stimulation train length to 35% with 100 pulses; this increase in [3H]‐noradrenaline was associated with falls in [3H]‐DOPEG and 3H‐non‐catechols. Generally the proportional increase in [3H]‐noradrenaline on stimulation was about 10 × total tritium when compared with the resting release.
The fractional release of [3H]‐noradrenaline per pulse was independent of train length, averaging about 6 × 10−6. This was reduced by the α2‐adrenoceptor agonist clonidine (0.3–30 nm) with an IC5o of 4.8 nm (10 pulses at 1 Hz).
The α2‐adrenoceptor antagonist, yohimbine (10–100 nm), did not alter the fractional release of [3H]‐noradrenaline elicited by 1 pulse. The antagonist did not change the amount or composition of the resting or evoked tritium overflow. However, yohimbine (l‐100 nm) increased the fractional release of [3H]‐noradrenaline per pulse for trains of 10 or 100 pulses (1 Hz) in a concentration‐dependent fashion. An increase above controls was significant only with 100 pulses and yohimbine, 30 nm.
The results show that the release of noradrenaline during trains of pulses in the mouse vas deferens can be regulated through presynaptic α2‐adrenoceptors. There was no evidence of inhibition by noradrenaline of its own release following a single pulse.
Twitch potentiation by organophosphate anticholinesterases in rat phrenic nerve diaphragm preparations
Authors: Clark Amanda L. , Hobbiger F. 
Published: July 2012

Twitch potentiation produced by anticholinesterases has been variously attributed to the prolonged postjunctional action of acetylcholine (ACh), a prejunctional action of ACh involving the initiation of antidromic firing (ADF) in the nerve or a direct action of the anticholinesterases on nerve terminals initiating ADF.
The organophosphate anticholinesterases, paraoxon (diethyl‐4‐nitrophenylphosphate) and DFP (diisopropyl fluorophosphate), when applied to rat isolated diaphragm preparations for 30 min, produced twitch potentiation which subsequently declined.
The rates of onset and decline of twitch potentiation were directly related to the concentration of the organophosphates and the reversibility of their effects was in line with the reactivation of the phosphorylated enzymes formed by them, whether reactivation was spontaneous or induced by the oxime, N,N'‐trimethylene‐1, 3‐bis (pyridinium‐4‐aldoxime).
Reducing the output of ACh from nerve terminals (by reducing the ratio of calcium: magnesium ions in the bathing solution) or reducing the affinity of ACh for the nicotinic cholinoceptor (using the disulphide bond reducing agent, dithiothreitol) produced the same effects as did lowering the concentration of the organophosphates.
It is concluded that the twitch potentiation produced by paraoxon and DFP, and its failure to be maintained when the higher concentrations of the organophosphates were used, were the direct result of the excess of ACh in the synaptic cleft, following inhibition of acetylcholinesterase.
Central nervous system effects of arachidonic acid, PGE2, PGF2α, PGD2 and PGI2 on gastric secretion in the rat
Authors: Puurunen Juhani 
Published: July 2012

The effects of arachidonic acid, prostaglandin E2 (PGE2), PGF2α, PGD2 and PGI2 on gastric secretion (acid, pepsin and volume) after intracerebroventricular administration were investigated in conscious, pylorus‐ligated rats.
Arachidonic acid 30–1000 μg had no effect on gastric secretion.
PGE2 3 and 10 μg, reduced gastric secretion as measured 1 hour after injection, although the inhibition induced by 3 μg disappeared by 2 h.
PGF2α 10 and 30 μg, inhibited gastric secretion as measured after 1 h, whereas no change was observed in the gastric contents collected 2 h after 10 μg of PGF2α. Intramuscular injection of 30 μg of PGF2α had no effect on gastric secretion.
Intracerebroventricular administration of 1–30 μg of PGD2 or PGI2 had no effect on gastric secretion.
The results indicate that PGE2 and PGF2α have a potent central antisecretory action in conscious, pylorus‐ligated rats, whereas arachidonic acid, PGD2 and PGI2 do not have any central effects on gastric secretion. It is suggested that PGE2 and PGF2α may be involved in the central nervous system control of gastric secretion.
The selectivity of β‐adrenoceptor antagonists on isoprenaline‐induced changes in heart rate, blood pressure, soleus muscle contractility and airways function in anaesthetized cats
Authors: Letts L.G. , Richardson D.P. , Temple Diana M. , Williams L.R. 
Published: July 2012

The β‐adrenoceptor antagonist activity of propranolol, metoprolol, atenolol and butoxamine in anaesthetized cats has been measured and compared with the activity of four synthetic phenylethanolamine derivatives.
The effects of isoprenaline on four parameters in the anaesthetized cat: heart rate, blood pressure, soleus muscle contractility and airway reactance, were measured and the modification of the isoprenaline dose‐response relation by each of the antagonist drugs assessed.
Parallel shifts in log dose‐response curves for isoprenaline were caused by propranolol for all parameters, by metoprolol and atenolol for each parameter except blood pressure, and butoxamine for each except soleus muscle and heart rate.
Selectivity of action of the antagonists between different organs was measured by comparing DR 10 values, computed from isoprenaline dose‐ratios.
Propranolol was the most potent antagonist and showed slight selectivity of action on soleus muscle compared with heart. Atenolol and metoprolol were approximately equipotent and were cardioselective at low doses only. Butoxamine was the least potent antagonist and possessed non‐β‐adrenoceptor effects on the parameters measured.
Each of the new compounds, 4′‐bromo‐2′‐methyoxy‐N‐isopropyl phenylethanolamine, the 4′‐chloro‐ and 4′‐methyl analogues, and 4′‐methoxy‐N‐t‐butyl phenylethanolamine, was a potent antagonist but did not exhibit any selectivity of action.
The results suggest no clear separation of β‐adrenoceptors into β1‐ and β2‐ subclasses in organs of the cat. There is no apparent separation of β‐adrenoceptor‐mediated effects on skeletal muscle and airways.
Inhibition by xanthine derivatives of adenosine receptor‐stimulated cyclic adenosine 3′, 5′‐monophosphate accumulation in rat and guinea‐pig thymocytes
Authors: Fredholm Bertil B. , Sandberg Göran 
Published: July 2012

The effect of stable adenosine analogues, including adenosine 5′‐N‐ethylcarboxamide (NECA) and N6‐l‐phenylisopropyl‐adenosine (l‐PIA), were studied on cyclic adenosine 3′, 5′‐monophosphate (cyclic AMP) accumulation in rat and guinea‐pig thymocytes.
NECA was approximately 10 times more potent than l‐PIA, in thymocytes from both species. d‐PIA was more potent in guinea‐pig than in rat thymocytes. The effect of a number of adenosine analogues followed the order: NECA > 2‐chloro‐adenosine > l‐PIA > N6‐cyclohexyl‐adenosine (CHA), an order of potency characteristic for adenosine receptors of the A2‐subtype. Thymocytes may be used as a model system to study the pharmacology of such receptors.
Several xanthines were studied as antagonists of the NECA (1 μm)‐induced cyclic AMP accumulation. The order of potency was: 1,3‐diethyl‐8‐phenylxanthine > 8‐phenyl‐theophylline > IBMX = 8‐p‐sulphophenyltheophylline = verrophylline > theophylline > caffeine > enprofylline > theobromine > pentoxiphylline. The pA2 value for 8‐phenyltheophylline was 0.35 μm, and the antagonism was shown to be competitive. The order of potency of the xanthine is virtually identical to that found earlier in several other systems in which the receptors are of the A1‐subtype. None of the xanthine derivatives tested thus seem to discriminate between A1 and A2‐receptor‐mediated adenosine actions.