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Dive into the research topics where Christine Ennis is active.

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Featured researches published by Christine Ennis.


Journal of Neurochemistry | 1981

Characterisation of Inhibitory 5-Hydroxytryptamine Receptors That Modulate Dopamine Release in the Striatum

Christine Ennis; Janet D Kemp; Barry Cox

Abstract: The effect of a series of indoleamines on the potassium‐evoked tritium release of previously accumulated [3H]dopamine from rat striatal slices has been investigated. The indoleamines 5‐hydroxytryptamine, 5‐methoxy‐tryptamine, 5‐methoxy‐N, N′‐dimethyltryptamine and tryptamine (10−7 to 10−3 M) all reduced potassium‐evoked release of tritium, to a maximum of 50%. The uptake of [3H]dopamine was unaffected by these compounds. A series of 5‐hydroxytryptamine antagonists were examined for their ability to reduce the inhibition of potassium‐evoked tritium release induced by 5‐methoxytryptamine. The relative order of antagonist potency obtained was methysergide > metergoline > methiothepin > cinanserin > cyproheptadine > mianserin, and was consistent with an action on 5‐hydroxytryptamine receptors. It is concluded that there are inhibitory 5‐hydroxytryptamine receptors located on the terminals of dopaminergic neurones in the striatum.


Journal of Neurochemistry | 2002

Characterisation of the Binding of [3H]WAY-100635, a Novel 5-Hydroxytryptamine1A Receptor Antagonist, to Rat Brain

Xavier Khawaja; Non Evans; Yvonne Reilly; Christine Ennis; Michael C. W. Minchin

Abstract: The specific binding of [3H]WAY‐100635 {N‐[2‐[4‐(2‐[O‐methyl‐3H]methoxyphenyl)‐1‐piperazinyl]ethyl]‐N‐(2‐pyridinyl)cyclohexane carboxamide trihydrochloride} to rat hippocampal membrane preparations was time, temperature, and tissue concentration dependent. The rates of [3H]WAY‐100635 association (k+1 = 0.069 ± 0.015 nM−1 min−1) and dissociation (k−1 = 0.023 ± 0.001 min−1) followed monoexponential kinetics. Saturation binding isotherms of [3H]WAY‐100635 exhibited a single class of recognition site with an affinity of 0.37 ± 0.051 nM and a maximal binding capacity (Bmax) of 312 ± 12 fmol/mg of protein. The maximal number of binding sites labelled by [3H]WAY‐100635 was ∼36% higher compared with that of 8‐hydroxy‐2‐(di‐n‐[3H]‐propylamino)tetralin ([3H]8‐OH‐DPAT). The binding affinity of [3H]WAY‐100635 was significantly lowered by the divalent cations CaCl2 (2.5‐fold; p < 0.02) and MnCl2 (3.6‐fold; p < 0.05), with no effect on Bmax. Guanyl nucleotides failed to influence the KD and Bmax parameters of [3H]WAY‐100635 binding to 5‐HT1A receptors. The pharmacological binding profile of [3H]WAY‐100635 was closely correlated with that of [3H]8‐OH‐DPAT, which is consistent with the labelling of 5‐hydroxytryptamine1A (5‐HT1A) sites in rat hippocampus. [3H]WAY‐100635 competition curves with 5‐HT1A agonists and partial agonists were best resolved into high‐ and low‐affinity binding components, whereas antagonists were best described by a one‐site binding model. In the presence of 50 µM guanosine 5′‐O‐(3‐thiotriphosphate) (GTPγS), competition curves for the antagonists remained unaltered, whereas the agonist and partial agonist curves were shifted to the right, reflecting an influence of G protein coupling on agonist versus antagonist binding to the 5‐HT1A receptor. However, a residual (16 ± 2%) high‐affinity agonist binding component was still apparent in the presence of GTPγS, indicating the existence of GTP‐insensitive sites.


Journal of Pharmacy and Pharmacology | 1979

Characterization of receptors on postganglionic cholinergic neurons in the guinea‐pig isolated ileum

Christine Ennis; P. A. J. Janssen; H. Schnieden; Brian Cox

Dopamine, apomorphine, noradrenaline and isoprenaline reduced the response of the isolated guinea‐pig ileum to exogenous acetylcholine by a maximum of 40%. Propranolol reversed this inhibition whilst phentolamine and pimozide were ineffective, suggesting that the drugs were acting on a post‐synaptic β‐adrenoceptor. The same agonists were more effective as inhibitors of the response to transmural electrical stimulation of the ileum, lower doses producing almost complete inhibition. This inhibition was partially antagonized by phentolamine, pimozide and propranolol. Clonidine proved to be the most potent inhibitor of the response to transmural electrical stimulation, whilst phenylephrine was ineffective. pA2 determinations showed that phentolamine was a potent antagonist of clonidine but a weak antagonist of apomorphine whilst for pimozide the opposite was true. The results suggest that there are two populations of prejunctional receptors on the cholinergic nerves innervating the smooth muscle of the guinea‐pig ileum. One receptor is similar to a classical prejunctional α‐adrenoceptor and the other resembles a central dopamine receptor.


Journal of Pharmacy and Pharmacology | 1982

Characterization of 5-hydroxytryptaminergic autoreceptors in the rat hypothalamus

Barry Cox; Christine Ennis

5‐hydroxytryptamine (5‐HT) (3 × 10−9 to 10−6 M) produced a concentration‐related inhibition of potassium‐evoked tritium release from slices of rat hypothalamus preloaded with [3H]‐5‐HT. The response to 5‐HT was unaffected by the presence of yohimbine (10−6 M), pimozide (10−7 M), domperidone (10−7 M) or tetrodotoxin (10−7 M), indicating that the response was not mediated via α1‐ or α2‐adrenoceptors or dopamine receptors and that the receptors that were involved were located directly on the 5‐HT nerve terminal. The 5‐HT antagonist metergoline (10−8 to 3 × 10−7 M) produced a parallel rightward shift in the concentration‐effect curve to 5‐HT with no reduction in the size of the maximum response. The pA10 value for metergoline was 6.82 and the slope of the Arunlakshana‐Schild plot was not significantly different from 1.0 indicating that it was a competitive antagonist. Methiothepin produced a similar effect to metergoline whilst cyproheptadine and methysergide were less potent as antagonists of 5‐HT and were not competitive. Cinanserin was inactive. Thus we have characterized the 5‐HT autoreceptor in the rat hypothalamus using a classical pharmacological approach and found that it has more in common with the autoreceptor which we have previously identified in the raphe nuclei of the rat than it has with the 5‐HT receptor located on dopamine neuroterminals in the striatum.


European Journal of Pharmacology | 1981

GABA enhancement of [3H]dopamine release from slices of rat striatum: Dependence of slice size

Christine Ennis; Barry Cox

The effect of GABA on potassium-evoked tritium release from two sizes of ribbon of rat striatum previously loaded with [3H]dopamine was studied. GABA had no effect on the release of tritium from 100 x 100 mum ribbons but produced a dose-related enhancement of potassium-evoked tritium release from 250 x 250 mum ribbons. The enhancement was unaffected by the presence of bicuculline or picrotoxin but was antagonised by tetrodotoxin. The effect of GABA was not mimicked by the GABA agonists muscimol or baclofen. The possible involvement of an interneurone is discussed. From antagonist studies the neurotransmitter released by the postulated interneurone did not appear to be acetylcholine, 5-hydroxytryptamine, glycine, glutamate or enkephalin.


Journal of Pharmacy and Pharmacology | 1986

Can the effects of meptazinol on the guinea‐pig isolated ileum be explained by inhibition of acetylcholinesterase?

Christine Ennis; Faizal Haroun; Norman Lattimer

It has previously been shown that there is a cholinergic component in the antinociceptive action of the opioid analgesic drug meptazinol. In the present study meptazinol was shown to be an inhibitor of acetylcholinesterase in‐vitro with a potency one hundredth that of physostigmine. This activity was found to reside only in the (−)‐enantiomer of meptazinol. The anticholinesterase activity of meptazinol may explain the increase in the size of the electrically‐evoked contraction of the guinea‐pig isolated ileum preparation since by using a long pulse width (5 ms) it was found that the (−)‐enantiomer of meptazinol modified only the component of the response due to neuronally released acetylcholine and had no direct effect on the smooth muscle. This property of meptazinol may also be responsible for the cholinergic effects of the drug in‐vivo.


British Journal of Pharmacology | 1980

MECHANISM OF ACTION OF DOPAMINE ON THE GUINEA-PIG GASTRO-OESOPHAGEAL JUNCTION in vitro

Barry Cox; Christine Ennis

1 The effect of dopamine on longitudinal muscle strips of the guinea‐pig isolated gastro‐oesophageal junction was compared with the response obtained to phenylephrine, isoprenaline and clonidine. Phenylephrine (5 × 10−7 to 5 × 10−5 m) produced a dose‐related contraction, whilst dopamine (10−6 to 10−4 m) and isoprenaline (5 × 10−7 to 2 × 10−5 m) produced dose‐related relaxations. Clonidine was ineffective in doses up to 10−5 m. 5‐Hydroxytryptamine (5‐HT) produced a contraction. 2 Phenylephrine was antagonized by α1‐adrenoceptor antagonists but unaffected by β‐adrenoceptor antagonists, whilst the opposite was the case for isoprenaline. A mixture of α‐ and β‐adrenoceptor antagonists was required to inhibit completely dopamine‐induced relaxations. 5‐HT (3 × 10−7 m) was specifically antagonized by methysergide (3 × 10−6 m). 3 pA2 values for a range of α‐adrenoceptor and dopamine receptor antagonists were determined against dopamine and phenylephrine. The relative order of potency of the antagonists was the same for both antagonists and was prazosin > spiroperidol > phentolamine > domperidone > haloperidol, with pimozide and metoclopramide being inactive. 4 Tyramine caused dose‐related relaxations of the gastro‐oesophageal strips which were susceptible to the same range of antagonists as dopamine. 5 Cocaine (6 × 10−6 m) and desmethylimipramine (3 × 10−7 and 10−6 m) reduced the relaxations induced by dopamine and tyramine but there were quantitative differences in the antagonism. 6 Tissue from reserpine pretreated guinea‐pigs was insensitive to tyramine but the response to dopamine was only partly reduced. 7 Histological examination of the strips revealed the presence of smooth muscle but only a sparse adrenergic innervation. 8 The results suggest that dopamine acts partly indirectly and partly directly on postjunctional α‐and β‐adrenoceptors. There is no evidence for an action on specific dopamine receptors.


British Journal of Pharmacology | 1983

Different alpha-adrenoceptors modulate the release of 5-hydroxytryptamine and noradrenaline in rat cortex.

Christine Ennis

1 The potassium‐evoked release of [3H] ‐noradrenaline from slices of rat occipital cortex and the potassium‐evoked release of [3H]‐5‐hydroxytryptamine from slices of rat frontal cortex were measured using a superfusion system. 2 The rank order of potency for a number of α‐adrenoceptor agonists was different for the two neuronal systems, Clonidine and azepexole being the most potent inhibitors of noradrenaline release and methoxamine and phenylephrine being the most potent against 5‐hydroxytryptamine release. 3 The rank order of potency for a series of α‐adrenoceptor antagonists in reversing the inhibition of noradrenaline release produced by Clonidine was: phentolamine > rauwolscine = yohimbine = corynanthine >> WB4101, whereas against methoxamine‐inhibition of 5‐hydroxytryptamine release the rank order of potency was: WB4101 > phentolamine > corynanthine > yohimbine > rauwolscine. 4 The results suggest that the α‐adrenoceptors which modulate potassium‐evoked 5‐hydroxytryptamine release are not identical with the α2‐adrenoceptors located on noradrenergic nerve terminals and may more closely resemble α1‐than α2‐adrenoceptors.


Journal of Pharmacy and Pharmacology | 1978

EFFECTS OF THE ANTIEMETIC DRUG DOMPERIDONE ON GUINEA-PIG ISOLATED GASTROINTESTINAL TISSUE

Christine Ennis; H. Schnieden; Brian Cox

Dopamine-receptor antagonists have antiemetic actions and have previously been presumed to act on the chemoreceptor trigger zone in the central nervous system. However, the dopamine-antagonists metoclopramide and domperidone have few central effects and yet are antiemetic. It seemed reasonable therefore to test whether there was a peripheral component in their action. communication (Ennis & others, 1977), dopamine was shown to inhibit cholinergic transmission in the isolated ileum preparation and it was thought possible that the antiemetics might act by preventing this action of dopamine on the cholinergic nerves of the gastrointestinal tract. However, in subsequent experiments domperidone was found to be inactive against this action of dopamine and therefore this could not explain its antiemetic action. Consequently we have been looking for alternative sites.


Journal of Pharmacy and Pharmacology | 1983

The release of 5‐hydroxytryptamine in the occipital and frontal cortex is modulated by different subtypes of α‐adrenoceptor

Christine Ennis

It has previously been reported that the potassium evoked release of 5-hydroxytryptamine (5-HT) from slices of rat frontal cortex was modulated by a-adrenoceptors which closely resemble the cw,-subtype (Ennis 1983). This finding however did not agree with those of Gothert et al (1981) who reported that the electrically evoked release of 5-HT from slices of rat occipital cortex was modulated by a,-adrenoceptors. There are therefore two variables which could account for the discrepency between the results of the two studies, i.e. (a) the region of the cortex that was used and (b) the method employed to depolarize the nerve terminals. The present study was designed to identify the type of a-adrenoceptor that modulates the release of 5-HT from slices of rat occipital cortex evoked by high external potassium concentrations, in an attempt to distinguish between these two variables.

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Barry Cox

University of Manchester

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Brian Cox

University of Manchester

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H. Schnieden

University of Manchester

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