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Biomedical subjects

D A Taylor

Publications and source records attributed to D A Taylor.

At least 163 records · Page 9Linked to original sources
PubMed1983

Spontaneously hypertensive rats exhibit an enhanced mydriatic response to clonidine. Evidence for enhanced sensitivity of central alpha 2-adrenoceptors.

Comparisons among spontaneously hypertensive (SHR), Kyoto Wistar (KW), and Wistar (W) rats were made of the functional states of central nervous system (CNS) alpha 2-adrenoceptors (clonidine-induced mydriasis) and nonvascular peripheral presynaptic alpha 2-adrenoceptors (clonidine-induced inhibition of the neurogenic twitch of the isolated vas deferens). While there were no differences among the strains of rats in the concentration of clonidine required to produce a 50% inhibition of the electrically evoked contractile response of the vas deferens, there was a significant reduction in the mean effective concentration (ED50) of clonidine to induce mydriasis in SHR as compared with KW and W rats. These observations indicate that CNS alpha 2-adrenoceptors may be functionally more sensitive in SHR. The data also suggest that the sensitivity of nonvascular presynaptic alpha 2-adrenoceptors, at least in the vas deferens, is not altered in hypertensive animals.

Animals↗
PubMed1983

Alcohol and mortality. Diagnostic considerations.

Two hundred fifty of 1289 alcoholics died within eight years of treatment of alcoholism or its complications. Gastrointestinal and cardiovascular disorders were significantly greater among the group who died within one year of treatment. Other sex, age and racial differences were also significant.

Adult↗
PubMed1983

Pharmacological characterization of purinergic receptors in the rat vas deferens.

Using the isolated rat vas deferens, we have confirmed the existence of P1 purinergic receptors whose activation results in an inhibition of the neurogenic twitch of the vas deferens. The observed order of potency for agonists (adenosine ethyl carboxamide greater than 2-chloroadenosine greater than adenosine greater than 5'-AMP greater than 5'-ADP greater than ATP) and antagonism of these effects by theophylline supports a P1-mediated response. Metabolically stable analogs of ATP elicited dose-dependent contractile responses which were quantitatively greater than, but qualitatively comparable to, ATP-induced responses. The order of potency for the eliciting contraction was the following: adenylyl-5-imidodiphosphate = beta-gamma-methylene ATP greater than adenosine tetraphosphate much greater than ATP greater than ADP. Interestingly, these compounds also produced an inhibition of the neurogenic twitch with a similar rank order of potency. This response was not due to the activation of P1 receptors insofar as high concentrations of theophylline failed to attenuate either the inhibition of the neurogenic twitch or the contractile response induced by these agonists. Thus, these data demonstrate the presence of both P1 and P2 purinergic receptors in the rat vas deferens. In addition, the data are consistent with the idea that two distinct classes of P2 receptors exist in this tissue. Furthermore, these data suggest that the rat vas deferens provides a useful tissue for studying compounds which interact with both major subtypes of purinergic receptors.

Adenosine↗
PubMed1982

Interaction of 2-phenylaminoadenosine (CV 1808) with adenosine systems in rat tissues.

2-Chloroadenosine (2-CADO) and 2-phenylaminoadenosine (CV 1808) were compared in a CNS purinergic receptor binding assay and the inhibition of neurogenic contractions of the vas deferens. Both 2-CADO and CV 1808 are more potent than adenosine in both preparations. CV 1808 was 10 times more active than dipyridamole in enhancing the response of the vas deferens to exogenous adenosine. Thus, CV 1808 may owe its potent coronary vasodilator activity to both a direct action on adenosine receptors and the ability to augment adenosine responses.

2-Chloroadenosine↗
PubMed1982

alpha 2-Adrenergic agonist and antagonist activity of the respective (-)-and (+)-enantiomers of 6-ethyl-9-oxaergoline (EOE).

The (-)-enantiomer of 6-ethyl-9-oxaergoline (EOE) inhibited contractions of the field-stimulated rat vas deferens in vitro, and produced mydriasis in anesthetized rats with an order of potency 1/2 and 1/5 that of clonidine, respectively. In contrast (+)-EOE competitively antagonized these responses to both (-)-EOE and clonidine with an order of potency 1/5 that of yohimbine. The data indicate that (-)- and (+)-EOE represent an unique example of enantiomers having opposing pharmacological activities upon alpha 2-adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1982

Alteration in the level of endogenous hypothalamic prostaglandins induced by delta 9-tetrahydrocannabinol in the rat.

1 Whole brain and regional brain levels of prostaglandin E2 (PGE2)-like material have been determined following administration of delta 9-tetrahydrocannabinol (delta 9 -THC) in rats. 2 Intravenous administration of delta 9-THC 2 mg/kg, resulted in marked behavioural changes and hypothermia. The behavioural changes consisted mainly of catatonia (most apparent at 30 min after administration of delta 9-THC), followed by sedation (most evident at 60 min). Hypothermia was marked from 30 min after administration of delta 9-THC. 3 delta 9-THC did not after the whole brain levels of PGE2-like material 30, 60 or 120 min after administration. 4 delta 9-THC did not alter the levels of PGE2-like material in the medulla oblongata/pons, midbrain, cortex and cerebellum, 30 min after administration. However, there was a significant reduction of PGE2-like material in the hypothalamus, 30 min after delta 9-THC. 5 It is suggested that the delta 9-THC-induced decrease in hypothalamic PGE2-like material may contribute to the hypothermia observed following delta 9-THC administration.

Animals↗
PubMed1982

Time-course of the effects of chronic delta 9-tetrahydrocannabinol on behaviour, body temperature, brain amines and withdrawal-like behaviour in the rat.

The effects of clomipramine HCl (15 mg kg-1 i.p.) on behaviour, body temperature and brain amines were investigated in rats that had been chronically treated twice daily with increasing doses of delta 9-tetrahydrocannabinol (delta 9-THC, 2-6 mg kg-1 i.v.). delta 9-THC produced a biphasic change in behaviour, stimulation followed by depression, and a pronounced hypothermia. Tolerance developed rapidly to these effects of delta 9-THC. Chronic treatment with delta 9-THC reduced the levels of homovanillic acid, 5-hydroxytryptamine and noradrenaline. The level of dopamine was not altered with chronic treatment and tolerance appeared to develop to the increased levels of 5-hydroxyindoleacetic acid induced by delta 9-THC. Injection of clomipramine, 12-14 h after 2, 5 or 10 days of delta 9-THC treatment induced characteristic changes in the rats behaviour which consisted of writhes, backward kicking, wet shakes, jumps ataxia and front paw and whole body tremor. The severity of the behavioural changes appeared to be dependent on the period of delta 9-THC administration and they were not accompanied by a change in body temperature or consistent changes in brain amines or metabolites. The results indicate that physical dependence on delta 9-THC may occur since clomipramine is able to precipitate changes in behaviour, indicative on an abstinence syndrome, in rats chronically treated with delta 9-THC. It is suggested that tryptaminergic mechanisms are altered during chronic delta 9-THC treatment and that clomipramine induces the behavioural changes by interacting with an altered tryptaminergic system.

Animals↗
PubMed1981

Attenuation of delta 9-tetrahydrocannabinol-induced withdrawal-like behaviour by delta 9-tetrahydrocannabinol.

Rats chronically treated with increasing daily doses of delta 9-tetrahydrocannabinol (delta 9-THC) for up to 5 or 10 days exhibit a withdrawal-like behavioural response when challenged with clomipramine, a potent inhibitor of serotonin (5-hydroxytryptamine) reuptake, at the time when the next injection of delta 9-THC was due. To determine whether this response is indeed a withdrawal syndrome, different groups of rats were injected IV twice daily for up to 5 days with either delta 9-THC, in doses increasing from 2-6 mg/kg, or polyvinyl-pyrrolidone (PVP), the vehicle in which delta 9-THC was suspended. On day 6, an acute dose of 6 mg/kg delta 9-THC was given 30 min before IP clomipramine (15 mg/kg). The total behavioural response, which included writhing, backward kicking, jumping, head shaking, and paw tremor, was attenuated in rats chronically treated with delta 9-THC, but not in rats which received an acute dose of PVP. These results lend further evidence to our hypothesis that chronically administered delta 9-THC produces a state of physical dependence in the rat.

Animals↗
PubMed1981

Neuropharmacological characterization of a taurine antagonist.

6-Aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1,1-dioxide hydrochloride (TAG) applied by microiontophoresis caused a prompt and readily reversible antagonism of the inhibitory effects of taurine and beta-alanine on rat somatosensory cerebral cortical neurons and cerebellar Purkinje neurons, although not affecting the actions of gamma-aminobutyric acid. TAG also consistently reduced, but did not abolish, the synaptically evoked inhibitions of Purkinje cells produced by electrical stimulation of the cerebellar surface. On the isolated amphibian spinal cord, TAG caused a dose-related enhancement of the dorsal root-ventral root potential, although not substantially affecting the dorsal root-dorsal root potential. Qualitative studies on the amphibian spinal cord showed that the depolarizing actions of taurine and beta-alanine on the dorsal roots, but not those of gamma-aminobutyric acid or glycine, were reduced by TAG. Somewhat surprisingly, TAG also offset the inhibitory effects on cortical cells and the dorsal root depolarizing actions of muscimol, 3-aminopropane sulfonic acid and piperidine-4-sulfonic acid, all of which heretofore have been considered as selective gamma-aminobutyric acid agonists. These findings would appear to lend a substantial degree of credence to the repeated suggestions that taurine may subserve a neurotransmitter-type function in the mammalian central nervous system. Furthermore, the availability of a relatively specific antagonist might reasonable be expected to facilitate efforts to elucidate the physiological functions of taurine not only in the central nervous system but in other organ systems in the body as well.

Action Potentials↗
PubMed1980

The action of adenosine on noradrenergic neuronal inhibition induced by stimulation of locus coeruleus.

Stimulation of locus coeruleus (LC) has been used to induce a noradrenergic inhibition of neurones in the rat cerebral cortex. The local application of adenosine or adenosine monophosphate by microiontophoresis in the cortex was found to produce a reduction of the evoked inhibition if the purine application was begun 20 sec before LC stimulation, but an enhancement of the inhibition if applied up to 35 sec after the LC stimulation. GABA increased the duration of LC inhibition irrespective of time of application. Adenosine and GABA showed no mutual potentiation, but norepinephrine increased the size of responses to both iontophoretic adenosine and GABA. The adenosine-norepinephrine interaction was synergistic, irrespective of the order of application. It is concluded that adenosine may act both presynaptically to inhibit, and postsynaptically to enhance the effects of noradrenergic neurone activation, the dominant effect observed depending on the temporal relationship between LC activation and adenosine application.

Adenosine↗
PubMed1980

Withdrawal-like behaviour induced by inhibitors of biogenic amine reuptake in rats treated chronically with delta 9-tetrahydrocannabinol.

The effects of the biogenic amine reuptake inhibitors fluoxetine, clomipramine and imipramine on the behaviour of rats after chronic treatment with delta 9-tetrahydrocannabinol (delta 9-THC) for 5 and 10 days were examined. Rats with permanently in-dwelling IV cannulae were injected twice daily with doses of delta 9-THC (2-6 mg/kg). delta 9-THC treatment reduced the rate of body weight gain and induced the typical biphasic modifications of behaviour. Tolerance developed to both of these effects. On days 6 and 11 of the experiment, rats were injected IP with 15 mg/kg imipramine HCl, clomipramine HCl or fluoxetine HCl, and behaviour, consisting of writhes, backward kicks, jumps and wet shakes, was observed for the next 30 min. Each of the amine reuptake inhibitors induced changes in behaviour, the severity of which appeared to correlate with their ability to inhibit the reuptake of 5-hydroxytryptamine (5-HT). It is suggested that tryptaminergic mechanisms are involved in the production of a withdrawal-like behaviour after chronic delta 9-THC treatment.

Animals↗
PubMed1980

A modified method for the isolation and determination of brain histamine using the Bio-Rex 70.

Bio-Rex 70, a weak cation exchange resin, has been used to specifically isolate histamine from rat brain tissue. This method compares favourably to other extraction procedures with respect to selectivity, reproducibility and time taken to perform the procedure. However, because it combines the optimum of these properties, it appears more adaptable for routine laboratory use. Following isolation, histamine is quantified fluorometrically after condensation with o-phthaldialdehyde (OPT). The sensitivity of the procedure allows for the chromatographic isolation, using Bio-Rex 70, of 12.5 ng histamine to give fluorescence twice that of blank. In addition, the use of Bio-Rex 70 enables the selective separation of histamine from fluorescent contaminants such as spermidine. The stability and the reproducibility of the adsorption and elution characteristics of Bio-Rex 70 enables the determination of 30 brain samples in a working day. This method has been applied to determine whole brain and regional brain levels of histamine in control and L-histidine-treated rats. The whole brain level of histamine, which was 50 ng/g, was increased by L-histidine and the highest concentration of histamine was found in the hypothalamus. Since the reliability of existing histamine extraction procedures is questionable, under certain conditions, it is suggested that the use of Bio-Rex 70 is a valuable addition in evaluating the possible physiological role of brain histamine.

Animals↗
PubMed1980

Electrophysiological actions of benzodiazepines.

Electrophysiological investigations have revealed that benzodiazepines, applied either locally or systemically, reduce central nervous system excitability. The studies summarized here indicate that this depression of excitability by benzodiazepines is a result of an increase in gamma-aminobutyric acid (GABA) mediated inhibition. This increase in inhibition may result from benzodiazepines increasing the activity of some GABAergic neurons and also from a modulatory action of benzodiazepines on GABA actions at some postsynaptic receptor sites. The modulatory action is observed with doses of benzodiazepines that do not cause any direct effects on neuronal excitability or membrane polarization. Specificity tests indicate that benzodiazepines do not enhance inhibition mediated by glycine or monoamines such as norepinephrine or serotonin. Results of experiments with a convulsant benzodiazepine compound, which causes a specific reduction in GABA-mediated inhibition, are also presented, The data are discussed in terms of a model in which the benzodiazepine receptor, the GABA receptor, and the chloride ionophore are functionally linked. Furthermore, it is proposed that some postsynaptic actions of GABA may be continually regulated by the occupancy of a benzodiazepine receptor, and that occupancy of the benzodiazepine receptor may be permissive for the GABA-elicited increase in chloride ion permeability.

Benzodiazepines↗