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B Collier

Publications and source records attributed to B Collier.

At least 55 records · Page 3Linked to original sources
PubMed1991

Stereospecificity of high- and low-affinity transport of choline analogues into rat cortical synaptosomes.

The present experiments used methylcholines to examine the stereoselectivity of choline transport into rat synaptosomes. R(+)-alpha-methylcholine and S(+)-beta-methylcholine were significantly better inhibitors of the high-affinity choline transport system than were their enantiomers. Although both enantiomers of alpha- and of beta-methylcholine inhibited [3H]choline transport, only R(+)-alpha-methylcholine and S(+)-beta-methylcholine could be transported by the high-affinity choline uptake mechanism. Therefore, we conclude that the chiral requirements for recognition of and for transport by the high-affinity transporter are clearly different. In addition to high-affinity choline transport, Na(+)-independent low-affinity transport was measured. This process transported R(+)-alpha-methylcholine, but not S(-)-alpha-methylcholine; however, it showed no stereoselectivity for the enantiomers of beta-methylcholine. Thus, high- and low-affinity choline transport mechanisms exhibit distinct differences in their substrate selectivities. We suggest that the stereoselective properties of choline transport might present a unique opportunity to study choline uptake and metabolism.

Animals↗
PubMed1990

Hypothalamic-pituitary-adrenal axis dysregulation among diabetic outpatients.

We compared insulin-requiring diabetic outpatients (n = 49) with normal controls (n = 42) for indices of hypothalamic-pituitary-adrenal (HPA) axis activity. Diabetic patients showed significantly elevated 9 a.m. plasma levels of cortisol as well as significantly elevated plasma levels of cortisol and adrenocorticotropic hormone (ACTH) at both 4 p.m. before and 4 p.m. after dexamethasone. Also, there was a significant correlation between postdexamethasone plasma levels of ACTH and duration of diabetes. These results suggest that HPA-axis dysregulation is found among diabetic outpatients. The possible psychiatric implications are discussed.

Adrenocorticotropic Hormone↗
PubMed1990

Evidence that somatostatin enhances endogenous acetylcholine release in the rat hippocampus.

The present experiments show that somatostatin (SS)-like immunoreactive material is present in the hippocampus and that its release can be increased by K+ stimulation of rat hippocampal slices, suggesting that SS-like peptides may be of significance to neurotransmission in the hippocampus. Exogenous SS-28 and SS-14 enhanced the K(+)-evoked release of endogenous acetylcholine (ACh) from rat hippocampal slices, whereas amino-terminal fragments of SS-28 did not. The increased ACh release in the presence of either peptide appeared to be mediated by an interaction with SS receptors because cyclo-SS, a putative SS antagonist, abolished the effects of both SS-28 and SS-14. In addition, the increase in ACh release induced by SS-14 or SS-28 was antagonized by the calcium channel antagonists omega-conotoxin GVIA, nifedipine, and cinnarizine, implicating voltage-sensitive calcium channels in this effect. Moreover, the effect was sensitive to tetrodotoxin, suggesting an indirect action of the peptides at a site distal to cholinergic nerve terminals. Cysteamine, which has been reported to deplete SS content and to increase SS release in brain, augmented the basal and evoked release of ACh from hippocampal slices, without affecting SS-like content and release. Finally, neuropeptide Y, which is colocalized with SS in many neurons of the hippocampal formation, did not alter ACh release, nor did it facilitate the SS-induced increase. The results suggest that in the rat hippocampus, both SS-28 and SS-14 interact with SS receptors to regulate ACh release indirectly by a mechanism that involves alterations of calcium influx during depolarization.

Acetylcholine↗
PubMed1990

Thymopoietin inhibits function and ligand binding to nicotinic receptors at the neuromuscular junction.

Thymopoietin is a 48 to 49 amino acid polypeptide hormone of the thymus, which regulates immune function. The present experiments show that the polypeptide can cause a complete block of transmission of the phrenic nerve diaphragm junction of the rat in vitro; contractile responses evoked by phrenic nerve stimulation were blocked by concentrations of thymopoietin as low as 10(-8) M. The thymopoietin-induced inhibition of indirectly evoked muscle contractions was dose- and time-dependent, with the polypeptide being only slightly less potent than alpha-bungarotoxin (alpha-BGT). Twitch responses to direct electrical stimulation of the muscle were not affected by thymopoietin, indicating that it did not inhibit muscle tension by an action on the muscle contractile mechanism per se. Furthermore, thymopoietin did not alter resting or stimulated release of acetylcholine from the phrenic nerve, suggesting that it did not interact at a presynaptic level. On the other hand, thymopoietin inhibited the binding of [125I]alpha-BGT to the nicotinic receptor of rat hemidiaphragm. In intact muscle tissue, the IC50 value for inhibition of [125I]alpha-BGT binding by thymopoietin was 2.1 x 10(-7) M, a value similar to the concentration of polypeptide required to inhibit phrenic nerve-induced muscle contraction (IC50 value, 0.75-1.6 x 10(-7) M). In a muscle membrane preparation, the potency of thymopoietin to affect [125I]alpha-BGT binding was increased (IC50 value, 0.35 nM); thus thymopoietin has the potential to interact at the nicotinic receptor in the nM range. To conclude, the present results show that thymopoietin inhibits neuromuscular activity by an effect that appears to be a specific interaction at the nicotinic receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1990

Effects of aging on nicotinic and muscarinic autoreceptor function in the rat brain: relationship to presynaptic cholinergic markers and binding sites.

The main objective of the present work was to determine whether the regulation of ACh release by nicotinic and muscarinic autoreceptors is compromised in the aged rat brain. For this, the effects of the nicotinic agonist N-methylcarbamylcholine (MCC) and the muscarinic-M2 antagonist AF-DX 116 on ACh release from brain slices of young (3-month-old), adult (9-month-old), and aged (27-month-old) rats were tested. The ability of MCC to enhance spontaneous ACh release in hippocampal, cerebral cortical, and cerebellar slices was only modestly altered with age. In contrast, the sensitivity of muscarinic autoreceptors in the aged hippocampus and cerebral cortex, but not the striatum, to blockade by the muscarinic-M2 antagonist AF-DX 116 was severely attenuated. To assess whether the age-related changes in cholinergic autoreceptor function may be due to deficits in presynaptic cholinergic markers, we tested whether choline acetyltransferase (ChAT) activity, basal and evoked ACh release, and nicotinic and muscarinic binding sites are altered in the aged rats. ChAT activity in forebrain regions was decreased in the aged compared to the young and mature adult rats. Furthermore, the potassium-evoked, but not the spontaneous, release of ACh was markedly depressed in striatal, hippocampal, and cortical slices of aged rats. The densities of nicotinic and muscarinic-M2 binding sites, assessed using 3H-MCC and 3H-AF-DX 116 as selective ligands, respectively, were markedly reduced in homogenates of the striatum, hippocampus, cerebral cortex, and thalamus of aged rats. In contrast, muscarinic-M1 sites, selectively labeled with 3H-pirenzepine, were not affected. Therefore, it appears that age-related decrements in ChAT activity and in muscarinic-M2, but not nicotinic, binding sites in the rat brain are reflected in a decreased function of muscarinic-M2 autoreceptors. However, the positive correlation between loss of ChAT activity, decreased muscarinic-M2 binding sites, and impaired muscarinic autoreceptor function is clearly tissue dependent.

Acetylcholine↗
PubMed1990

Probe amplifier system based on chimeric cycling oligonucleotides.

Amplification systems are required as part of DNA probe technology, since traditional non-amplified oligonucleotide hybridization using nonradioactive detection methods have detection limits of approximately 10(8) molecules. We present a probe amplifier technology suitable for use in large-scale automated clinical diagnostic systems. It is fast, sensitive and performs at a constant temperature. The system functions by allowing a single target molecule to act as a catalyst in converting a large number of probe molecules to a unique detectable form. We refer to this catalytic amplification process as the "cycling probe reaction." The basis of the system is an oligomer probe construction consisting of a DNA-RNA-DNA sequence.

Base Sequence↗
PubMed1989

Pharmacological activity of N-methyl-carbamylcholine, a novel acetylcholine receptor agonist with selectivity for nicotinic receptors.

N-Methyl-carbamylcholine (also called N-methyl-carbachol) is an analogue of the mixed muscarinic-nicotinic acetylcholine receptor agonist, carbachol. Previous studies have provided evidence that radiolabelled N-methyl-carbachol can bind selectively to nicotinic acetylcholine receptors in rat brain. To determine whether N-methyl-carbachol acts as an agonist or an antagonist at nicotine and/or muscarinic receptor sites, the present study examined the pharmacological activity of this compound on some cholinergically innervated tissues. N-Methyl-carbachol, like carbachol, depolarized rat isolated sympathetic ganglia and these effects were inhibited by a nicotinic antagonist, d-tubocurarine, but not by a muscarinic antagonist, atropine. Exposure of rat sympathetic ganglia to N-methyl-carbachol blocked the compound action potential generated in ganglia by stimulation of the pre-ganglionic trunk; this effect of N-methyl-carbachol was likely due to desensitization of the nicotinic response. N-Methyl-carbochol, like carbachol, stimulated the release of [3H]noradrenaline from cultured adrenal medullary cells that had been pre-loaded with [3H]noradrenaline; these effects were largely inhibited by a nicotinic antagonist, mecamylamine, while atropine produced less blockade. N-Methyl-carbachol contracted the frog isolated rectus abdominis muscle and the effect was completely blocked by d-tubocurarine. By contrast, contracture of the rectus abdominis produced by carbachol was partially inhibited by either atropine or d-tubocurarine. N-Methyl-carbachol, like carbachol, contracted the rat isolated ileum and these effects were completely blocked by atropine; however, N-methyl-carbachol was about 42 times less potent than carbachol for this effect. Intravenous injection of N-methyl-carbachol, like nicotine, to the rat produced a transient decrease followed by a more sustained rise in blood pressure while carbachol produced only a sustained decrease in blood pressure. The effects of N-methyl-carbachol and nicotine on blood pressure were blocked by pretreatment of the animal with a nicotinic antagonist, hexamethonium. N-methyl-carbachol, like nicotine, stimulated the release of [3H]dopamine from rat striatal synaptosomes, pre-loaded with [3H]dopamine; release induced by either N-methyl-carbachol or nicotine was inhibited by mecamylamine but not by atropine. In rat cerebral cortical slices pre-loaded with [3H]inositol, carbachol, but not N-methyl-carbachol, stimulated the accumulation of [3H]inositol-1-phosphate, an effect blocked by atropine but not by mecamylamine.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Medulla↗
PubMed1989

Localization of interleukin-2 immunoreactivity and interleukin-2 receptors in the rat brain: interaction with the cholinergic system.

The present work characterizes the presence of interleukin-2 (IL-2)-like immunoreactive material and IL-2 binding sites in the adult rat brain. The results show that there are detectable levels of IL-2-like material in extracts of rat hippocampus, striatum, and frontal cortex. However, specific [125I]IL-2 binding sites were observed only in the hippocampus, using both homogenate-binding and autoradiographic techniques. In this region of the rat brain, specific [125I]IL-2 binding was inhibited by 100 nM non-radioactive recombinant human IL-2. In kainate-lesioned hippocampi, the density of [125I]IL-2 sites was apparently increased, suggesting their localization to extrinsic innervation and/or glial cells. In slices of hippocampus, which contain both IL-2-like immunoreactive material and specific IL-2 sites, exogenous IL-2 significantly decreased the potassium (25 mM)-evoked, but not the basal, release of acetylcholine. This IL-2-induced effect was concentration-dependent, and was apparent at a relatively low concentration (1 nM). This IL-2 effect was also region-specific, such that acetylcholine release from other tissue slices (striatal, frontal cortical) was not affected. In slices from kainate-lesioned hippocampi, the IL-2-induced reduction of acetylcholine release was only modestly enhanced, suggesting that the extra IL-2 sites that appear post-lesion may not be localized to cholinergic terminals.

Acetylcholine↗
PubMed1989

Binding sites for [3H]AF-DX 116 and effect of AF-DX 116 on endogenous acetylcholine release from rat brain slices.

The present study shows that the putative M2 ligand, [3H]AF-DX 116, binds to two classes of muscarinic sites in homogenates of rat hippocampus, striatum and cerebral cortex: one with a high affinity (Kd less than 5 nM)/low capacity (Bmax = 30-63 fmol/mg protein), and a second of lower affinity (Kd greater than 65 nM) and higher capacity (Bmax greater than 190 fmol/mg protein). In experiments which tested the effects of the muscarinic antagonists on acetylcholine (ACh) release from brain slices, the non-selective antagonist (-)-quinuclidinyl benzylate and atropine significantly enhanced the potassium (25 mM)-evoked release of ACh. This effect was mimicked by the M2 ligand AF-DX 116, but neither the M1-selective antagonist pirenzepine, nor the putative M3-muscarinic antagonist, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP), altered ACh release. Also, the muscarinic agonist, oxotremorine, significantly depressed evoked ACh release from brain slices, an effect that was completely antagonized by atropine or by AF-DX 116, but not by pirenzepine or 4-DAMP. Thus, it appears that presynaptic muscarinic autoreceptors in the rat hippocampus, striatum and cerebral cortex belong to the M2 subtype of muscarinic receptors.

Acetylcholine↗
PubMed1989

Insulin-like growth factor-1 (somatomedin-C) receptors in the rat brain: distribution and interaction with the hippocampal cholinergic system.

The present work characterizes the autoradiographic distribution of insulin-like growth factor-1 (IGF-1)/somatomedin-C binding sites in neonatal and adult rat brain, and attempts to correlate the distribution of IGF-1 sites, in certain regions of the rat brain, with functional IGF-1 receptors. In neonatal brain, [125I]IGF-1 binding sites are especially concentrated in superficial cortical layers, nucleus accumbens and hippocampus. In the adult rat brain, the distribution of IGF-1 sites is broader, with a high density of sites observed in superficial and deep cortical layers, olfactory bulb, endopiriform nucleus, basomedial nucleus of the amygdala, thalamic nuclei and hippocampus. Specific binding of [125I]IGF-1 to its sites in these brain regions was almost completely inhibited by 100 nM nonradioactive IGF-1. In contrast, similar concentrations of either IGF-2 or insulin did not significantly alter [125I]IGF-1 binding to its sites. Therefore, under our incubation conditions, [125I]IGF-1 appears to label specifically the type-I IGF receptor. In the hippocampus, which is highly enriched with specific [125I]IGF-1 binding sites in both neonatal and adult rat brain, IGF-1 significantly altered the potassium-evoked (25 mM) release of acetylcholine (ACh) from slices of adult, but not immature (6- and 18-day-old), rat brain. This IGF-1-induced decrease in ACh release from adult rat brain slices was concentration-dependent and appeared to be specific to hippocampus; ACh release from frontal cortical slices was not affected by this GF. The spontaneous release of ACh in the presence of IGF-1 in either tissue was not significantly different from control.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1989

Regulation of endogenous acetylcholine release from mammalian brain slices by opiate receptors: hippocampus, striatum and cerebral cortex of guinea-pig and rat.

The effects of opiate agonists on acetylcholine release from hippocampal, striatal and cerebral cortical slices were tested; tissue from rat was compared to that from guinea-pig. The results show that opiate receptors in each of these areas can alter the evoked release of acetylcholine from nerve terminals; however, there are species and tissue differences with respect to the apparent subtype of opiate receptor effective. In the hippocampus and striatum of the two species studied, opiates caused a dose-dependent decrease in evoked acetylcholine release from tissue slices but in the guinea-pig kappa-selective agonists were effective, and mu or delta agonists were not, whereas in the rat, mu-, but not delta- or kappa-selective drugs were effective. Opiates also altered acetylcholine release from the frontal, parietal and occipital cortex of both of these species. In all three regions of the guinea-pig cortex, kappa and delta agonists were active and in the parietal cortex mu agonists were also active; rat cortical slices showed similar results except that delta agonists were not effective. The inhibitory effects of the opiate agonists were effectively antagonized by the non-selective opiate antagonist naloxone and by the calcium channel agonists, BAY K 8644 or YC-170. In addition, the effects of the opiate drugs tested in this study on acetylcholine release were confined to evoked release, that is, spontaneous acetylcholine release was not affected. The results suggest that in guinea-pig and rat brain, opiate receptors regulate acetylcholine release, and that, although the subtypes of opiate receptors involved in this effect are different in the two species and in different tissues from the same species, the effect results from a common mechanism that involves alterations of calcium influx into the nerve terminals during depolarization.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1989

Progress report on the Canadian Multicentre Trial of tetrahydroaminoacridine with lecithin in Alzheimer's disease.

Since the discovery of a significant depletion of acetylcholine in discrete areas of the brain of patients affected by Alzheimer's disease, attempts at symptomatic therapy have concentrated on acetylcholine supplementation, an approach that is based upon the efficacy of dopaminergic supplementation therapy for Parkinson's disease. Choline, then lecithin, used orally, failed to improve symptoms but the hypothesis that long-term choline supplementation might stabilize the course of Alzheimer's disease remains to be tested. Nerve growth factor may also offer that possibility. Bethanechol administered intracerebroventricularly did not help when a fixed dose was used but individual titration of more selective muscarinic agonists may prove more effective. In this article we report that tetrahydroaminoacridine (THA), given together with highly concentrated lecithin, appears to bring improvement in cognition and in functional autonomy using the Mini Mental State and the Rapid Disability Rating Scale-2 respectively, without change in behavior as reflected by the Behave-AD. Double-blind cross-over studies are in progress to establish its efficacy. Improvement in study design and means of assessment of cognition, functional autonomy and behavior have been made possible by these drug trials.

Aged↗
PubMed1989

Nutritional factors in diabetics with and without retinopathy.

We used 3-d food-record-keeping techniques to examine nutritional factors in diabetic patients with and without retinopathy. Patients without retinopathy had significantly higher daily intakes of total carbohydrate, water-soluble dietary fibers, insoluble dietary fibers, and glucose than did patients with retinopathy. Also, patients without retinopathy took a significantly lower proportion of their total daily calories as protein.

Adult↗
PubMed1989

Acetylcholine synthesis by a sympathetic ganglion in the presence of 2-(4-phenylpiperidino)cyclohexanol (AH5183) and picrylsulfonic acid.

The present experiments measured the release and the synthesis of acetylcholine (ACh) by cat sympathetic ganglia in the presence of 2-(4-phenylpiperidino)cyclohexanol (AH5183 or vesamicol) and/or picrylsulfonic acid (TNBS), two compounds known to have the ability to block the uptake of ACh by cholinergic synaptic vesicles in vitro. We confirmed that, in stimulated (5 Hz) perfused (30 min) ganglia, AH5183 depressed ACh release and ACh tissue content increased by 86 +/- 6% compared to contralateral ganglia used as controls. Preganglionic activity increased ACh release by a similar amount in the presence (19.9 +/- 1.0 pmol/min) or absence (20.5 +/- 2.4 pmol/min) of TNBS. The final tissue ACh content was also similar in the presence (1,668 +/- 166 pmol) or absence (1,680 +/- 56 pmol) of TNBS. However, the AH5183-induced increase of tissue ACh content (86 +/- 6%) was abolished completely when AH5183 was perfused with 1.5 mM TNBS (-3.0 +/- 1.0%). This inhibition of ACh synthesis, observed in TNBS-AH5183-perfused ganglia, was not dependent upon further inhibition of ACh release beyond that caused by AH5183 alone, because 14.0 +/- 1.9% of the transmitter store was released by preganglionic nerve stimulation in the presence of TNBS plus AH5183 and this was similar in the presence of AH5183 without TNBS (14.0 +/- 0.6%). Moreover, when ganglia were first treated with TNBS and then stimulated in the presence of AH5183, an increase of 64 +/- 6% of the ganglionic ACh content occurred, and this increase was not statistically different from the increase measured with AH5183 alone (86 +/- 6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1989

Effect of chronic nicotine treatment on nicotinic autoreceptor function and N-[3H]methylcarbamylcholine binding sites in the rat brain.

It has been reported that N-methylcarbamylcholine (MCC), a nicotinic agonist, binds to central nicotinic receptors and causes an increase of acetylcholine (ACh) release from certain central cholinergic nerve terminals. The present experiments determine whether these two phenomena change in response to the chronic administration of nicotine, a procedure known to result in an increase in nicotinic binding sites. Chronic nicotine caused a brain region-specific up-regulation of [3H]MCC sites; binding increased in the frontal cortex, parietal cortex, striatum, and hippocampus, but not in the occipital cortex or cerebellum. The effect of nicotine was selective to nicotinic binding sites, because muscarinic sites, both M1 ([ 3H]pirenzepine) and M2 ([3H]ACh), were unaffected by chronic nicotine treatment. MCC increased the release of ACh from the frontal cortex and hippocampus by a calcium-dependent mechanism; MCC did not alter ACh release from striatum or occipital cortex of control animals. The MCC-induced increase in ACh release was not apparent in those animals which had been treated with nicotine. There was a partial recovery of nicotinic autoreceptor function when animals were allowed to recover (4 days) following chronic nicotine treatment, but the density of binding sites remained increased compared to control. Chronic nicotine did not change the potassium-evoked release of ACh from the frontal cortex or hippocampus, but decreased this measure from striatum. It also decreased the ACh content of the striatum, but not that of the cortex or the hippocampus; the activity of choline acetyltransferase was not altered in any of the regions tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗