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Biomedical subjects

D A Taylor

Publications and source records attributed to D A Taylor.

At least 145 records · Page 8Linked to original sources
PubMed1986

In vivo and in vitro activity of selective 5-hydroxytryptamine2 receptor antagonists.

The abilities of ketanserin, ritanserin, R56413 and LY53857 to inhibit 5-hydroxytryptamine (5-HT) and noradrenaline-induced vasoconstrictor responses both in vitro and in vivo and to lower blood pressure in the rat, were compared. In the isolated perfused mesenteric artery preparation of the rat all of the compounds tested were found to be potent inhibitors of 5-HT-induced vasoconstrictor responses. Ritanserin was the most potent compound, producing more than 50% inhibition of a near maximal response to 5-HT at a concentration of 10(-11) M. All four compounds were found to be competitive antagonists of noradrenaline; ketanserin being the most potent with a pA2 value of 7.64 +/- 0.06. 5-HT-induced pressor responses in the pithed rat were inhibited by low doses (0.3-10 micrograms kg-1) of the four compounds. Ketanserin, at doses of 0.1-3.0 mg kg-1, resulted in rightward shifts of the control dose-response curve to noradrenaline in the pithed rat. None of the other compounds had any significant effect on the noradrenaline-induced pressor responses. Ketanserin (0.1-1 mg kg-1) produced a dose-dependent decrease in the mean arterial blood pressure of anaesthetized rats. The maximum decrease in blood pressure observed following a dose of 1 mg kg-1 ketanserin was 73.7 +/- 4.7 mmHg. The other compounds at doses of 1.0-3.0 mg kg-1 produced a decrease in blood pressure of a lesser magnitude than that following ketanserin. In addition, this effect did not appear to be dose-dependent. It is suggested that the acute hypotensive effect of ketanserin results predominantly from alpha 1-adrenoceptor blockade. The involvement ofantagonism of 5-HT2 receptors in the hypotensive effect of the other compounds tested cannot be excluded.

Anesthesia↗
PubMed1985

Use of phosphorothioate analogs of poly(dA-dT).poly(dAdT) to study steroidal-diamine induced conformational change in poly(dA-dT).poly(dA-dT).

Introduction of phosphorothioate groups into the backbone of poly(dA-dT) allows one to label the d(ApT) and d(TpA) phosphate resonances in the 31P NMR spectrum. Upon binding the steroidal diamine dipyrandenium to poly d(AsT) and poly d(TsA), 31P NMR shows that it is the d(ApT) phosphodiester bond which is most perturbed. Other work has shown that 2 M Cs+ causes the same 31P shift. The DNA conformational change induced by both cations probably involves a narrowing of the minor groove.

Magnetic Resonance Spectroscopy↗
PubMed1985

Evidence for sequence-specific conformational changes in DNA from the melting temperatures of DNA phosphorothioate derivatives.

Analogs of alternating purine-pyrimidine DNA polymers such as poly(dA-dT)-poly(dA-dT) can be made with phosphorothioate groups in the DNA backbone. A phosphorothioate diester at the 5'-purine-pyrimidine-3' step causes a significant lowering of the polymer's melting temperature compared to a phosphorothioate diester at the 5'-pyrimidine-purine-3' step. This may occur because sulfur substitution increases anionic charge density in the DNA minor groove and 5'-purine-pyrimidine-3' steps narrow the minor groove. The ability to modulate charge density in the DNA backbone via sulfur substitution should prove useful in studies of sequence-dependent conformational changes in DNA.

Crystallization↗
PubMed1985

Involvement of brain histamine in delta 9-tetrahydrocannabinol tolerance and withdrawal.

The involvement of brain histamine (HA) in delta 9-tetrahydrocannabinol (delta 9-THC) tolerance and dependence was studied in rats. Rats treated for 5 days with delta 9-THC (2-6 mg/kg, IV) developed tolerance to the hypothermic effects of the drug. Tolerance also developed over the 5 day period to the decrease in brain regional HA concentrations observed after an acute injection of delta 9-THC. Administration of the tricyclic antidepressant drug clomipramine hydrochloride to tolerant rats induced a withdrawal-like behavioural syndrome. Accompanying this behaviour was a fall in HA concentrations of the midbrain, cortex, medulla oblongata/pons and the cerebellum. Administration of delta 9-THC, but not of the delta 9-THC vehicle, prior to clomipramine challenge attenuated both the intensity of the withdrawal-like syndrome and the reductions in brain regional HA concentration.

Animals↗
PubMed1985

Selectivity of (+)-4-propyl-9-hydroxynaphthoxazine [(+)-PHNO] for dopamine receptors in vitro and in vivo.

The intrinsic activity of the potent dopamine (DA) agonist 4-propyl-9-hydroxynaphthoxazine [(+)-PHNO] was examined in receptor binding assays for the following receptors: DA, alpha-1 and alpha-2 adrenergic, serotonin-1 and -2, neuroleptic, beta adrenergic, anxiolytic, adenosine A-1, gamma-aminobutyric acid, muscarinic and opiate. (+)-PHNO exhibited strong to moderate potencies [IC50 (nanomolars) in parentheses] in binding to DA (24), "neuroleptic" (67), alpha-2 adrenergic (77) and serotonin-1 (277) sites. The pharmacological activity of the naphthoxazine both in vivo and in vitro was contrasted with the known DA agonists apomorphine, pergolide, lisuride and 6-ethyl-9-oxaergoline in tests of DA, alpha-2 adrenergic and serotonergic function. Each compound was examined in vitro in receptor binding assays for interactions with DA, alpha-2 adrenergic, serotonin-1 and serotonin-2 receptors and for alpha-2 adrenergic activity in inhibiting field-stimulated contractions of the vas deferens of the rat. In vivo, alpha-2 adrenergic activity was assayed via measurement of mydriasis after i.v. injections in the rat, whereas serotonin activity was assayed by measuring drug-induced inhibition of 5-hydroxytryptophan accumulation, and DA activity was assessed by quantifying stereotyped behavior after both i.p. and i.v. injections. Selectivity ratios for the DA receptor were derived from effective dose values determined in these tests and demonstrated that only apomorphine was more selective as a DA agonist than (+)-PHNO in vivo. (+)-PHNO was the least active agent at the alpha-2 receptors in the vas deferens and with serotonergic mechanisms in vivo to reduce 5-hydroxytryptophan accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Serial lumbar punctures for at least temporary amelioration of neonatal posthemorrhagic hydrocephalus.

Serial lumbar punctures for the management of neonatal posthemorrhagic hydrocephalus without intracranial hypertension were evaluated in 16 infants. Cranial ultrasonography to evaluate ventricular size and the Ladd monitor at the anterior fontanel to measure intracranial pressure were utilized immediately before and after lumbar puncture. In 12 patients, a decrease in ventricular size and in anterior fontanel pressure could be effected with each lumbar puncture. In these infants, cessation of progression of the hydrocephalus and intermittent decreases in ventricular size were accomplished. In four patients, lumbar punctures were not successful in decreasing ventricular size or lowering intracranial pressure. Two criteria could be defined to determine whether lumbar puncture could provide at least temporary benefit for the treatment of posthemorrhagic hydrocephalus. The first of these is to establish the presence of communication between lateral ventricles and lumbar subarachnoid space by effecting a decrease in ventricular size and a decrease in intracranial pressure by removal of CSF. The second criterion is to ascertain a critical volume of CSF (usually relatively large) that must be removed in order to effect the above changes. Cranial ultrasonography and measurement of intracranial pressure by application of the Ladd monitor to the anterior fontanel are extremely valuable in the evaluation of lumbar punctures in the management of posthemorrhagic hydrocephalus.

Cerebral Hemorrhage↗
PubMed1985

Surgical sympathectomy of the heart in rodents and its effect on sensitivity to agonists.

A new procedure for sympathetic denervation of the hearts of rats and guinea pigs is described. Bilateral removal of the inferior and medial cervical ganglia results in almost complete loss of catecholamines from atria and ventricles, disappearance of catecholamine-associated histofluorescence from the region of the sinoatrial node and marked depression of the chronotropic concentration-response curve for tyramine in right atria of both species. Seven days after bilateral sympathectomy, the chronotropic concentration-response curve for isoproterenol is shifted to the left by a factor of 3.3 in the rat and 1.7 in guinea-pig right atria. The chronotropic concentration-response curve for histamine was not shifted by sympathectomy in the guinea-pig right atrium. Inasmuch as the rat atrium does not respond to histamine, similar experiments could not be done in the rat. The inotropic concentration-response curve for isoproterenol in electrically driven left atria was not affected by 7 days of sympathectomy in either species. These results indicate that chronic surgical sympathectomy of the heart can be successfully accomplished in the rat and guinea pig. Such sympathectomy induces a postjunctional supersensitivity in guinea-pig right atria which is qualitatively and quantitatively similar to that described previously for chronic treatment with reserpine. Bilateral surgical sympathectomy provides a valuable tool for future investigations of the cellular basis of supersensitivity in the myocardium.

Animals↗
PubMed1984

Antagonism by ketanserin of 5-HT-induced vasoconstriction unmasks a 5-HT-induced vasodilation.

The effect of ketanserin on the action of 5-hydroxytryptamine (5-HT) and noradrenaline has been studied using the rat isolated perfused mesentery preparation. Both 5-HT and noradrenaline produced constriction in the mesenteric vessels. The responses to 5-HT and noradrenaline were greater in tissues from hypertensive animals. Responses to 5-HT were abolished by 1 nM ketanserin. Ketanserin was found to be a competitive antagonist of the noradrenaline-induced constrictions (pA2 = 7.5). In partially constricted tissues, 5-HT induced vasoconstriction and vasodilation. In the presence of ketanserin the vasoconstriction was reduced and the 5-HT-induced vasodilation was potentiated. The amount of potentiation of the 5-HT-induced vasodilation by ketanserin was similar in tissues from normotensive and hypertensive rats. It is suggested that the 5-HT-induced vasoconstriction is mediated by activation of 5-HT2 receptors. In the presence of ketanserin, the 5-HT2 receptor mediated vasoconstriction is antagonized, unmasking a 5-HT-induced vasodilation.

Amidines↗
PubMed1984

Representation of linear orders.

Two binary classification tasks were used to explore the associative structure of linear orders. In Experiment 1, college students classified English letters as targets or nontargets, the targets being consecutive letters of the alphabet. The time to reject nontargets was a decreasing function of the distance from the target set, suggesting response interference mediated by automatic associations from the target to the nontarget letters. The way in which this interference effect depended on the placement of the boundaries between the target and nontarget sets revealed the relative strengths of individual interletter associations. In Experiment 2, students were assigned novel linear orders composed of letterlike symbols and asked to classify pairs of symbols as being adjacent or nonadjacent in the assigned sequence. Reaction time was found to be a joint function of the distance between any pair of symbols and the relative positions of those symbols within the sequence. The effects of both distance and position decreased systematically over 6 days of practice with a particular order, beginning at a level typical of unfamiliar orders and converging on a level characteristic of familiar orders such as letters and digits. These results provide an empirical unification of two previously disparate sets of findings in the literature on linear orders, those concerning familiar and unfamiliar orders, and the systematic transition between the two patterns of results suggests the gradual integration of a new associative structure.

Adult↗
PubMed1984

Knowledge of strategies for the expression of emotion among normal and maladjusted boys: a research note.

Younger (7-8 years) and older (10-11 years) boys from normal schools and from schools for the maladjusted were given two tests to assess their knowledge of strategies of control for both facial and overt behavioural expression of a negative emotion. The results indicated firstly that there is a developmental change in the spontaneous mention of a display rule with this developmental trend being retarded amongst the maladjusted boys. Secondly, there was a difference between the normal and maladjusted boys' knowledge of strategies for control of behaviour in a conflict situation.

Affect↗
PubMed1984

Competitive antagonism of alpha 1-adrenoceptor mediated pressor responses in the rat mesenteric artery.

(-)-Noradrenaline-mediated pressor responses in the rat mesenteric artery preparation are blocked by alpha 1-adrenoceptor antagonists, BE2254 and prazosin with pA2 values of 8.59 and 8.52 respectively. The alpha 2-adrenoceptor selective antagonist rauwolscine, does not influence responses to (-)-noradrenaline in concentrations up to 10 microM. This rank order is consistent with an alpha 1-adrenoceptor mediated effect. Shifts in the (-)-noradrenaline dose-response curve produced by BE2254 and prazosin were parallel and there was no significant effect on the observed maximal response. Slope values from Schild plots were not significantly different from unity indicating that these antagonists were behaving as classical competitive antagonists.

Adrenergic beta-Antagonists↗
PubMed1984

Chronic lead exposure of the developing brain: electrophysiological abnormalities of cerebellar Purkinje neurons.

This manuscript reviews our recent research concerning electrophysiological effects of chronic low-level lead exposure on developing brain. We found that, although growth, survival and histological organization of in oculo cerebellar grafts appear normal after perinatal exposure to blood lead levels of 450 to 550 micrograms/liter, the physiological activity of Purkinje neurons in these lead-treated grafts is abnormally low after discontinuation of lead treatment. On the other hand, chronic low-level lead exposure postnatally via systemic injections or perinatally via the drinking water did not alter in situ cerebellar Purkinje cell activity. Moderate systemic doses (2 mg/kg) did cause a persistent slowing of Purkinje neuron firing rates; however, this effect was much smaller than in intraocular cerebellar grafts. The slowing may be mediated by lead actions on various transmitter systems. We have found that chronic lead induces catecholaminergic neurons to hyperinnervate target areas. Perhaps this hyperinnervation is initiated by the postsynaptic lead-induced blockade of the electrophysiological effects of norepinephrine which we have previously observed in the cerebellum in situ and in cerebellar grafts in oculo.

Action Potentials↗
PubMed1984

L-646,462, a cyproheptadine-related antagonist of dopamine and serotonin with selectivity for peripheral systems.

The selectivity, peripheral vs. central actions, of the antidopaminergic agent L-646,462 was assessed in two ways. First, elevation of prolactin in serum (peripheral) and homovanillic acid in the striatum were measured in rats. L-646,462 was found to have a central/peripheral activity ratio of 143, whereas comparable values derived for haloperidol, metoclopramide and domperidone were 1.4, 9.4 and 1305, respectively. Second, the ID50 values required to block apomorphine-induced emesis in beagles (peripheral receptor-mediated response) were compared with those required to block apomorphine-induced stereotypy (central receptor-mediated response) in rats. Central/peripheral ID50 ratios of 234, 9.2, 129 and 7040 were obtained, respectively, for L-646,462, haloperidol, metoclopramide and domperidone. The selectivity of L-646,462 for peripheral serotonin (5-HT) receptors in rats was determined by measuring its effectiveness in blocking 5-HT-induced paw edema (peripheral response) and 5-hydroxytryptophan-induced head twitch (central response); a ratio of 114 was obtained. This value agrees nicely with the ratio of 143 derived in the rat ( vide supra) for peripheral selectivity for dopamine receptors. L-646,462 is, therefore, selective in vivo, preferentially blocking dopamine and 5-HT receptors located outside the blood-brain barrier. With regard to dopamine-receptors, L-646,462 was about equipotent and more selective than metoclopramide, while being less potent and less selective than domperidone. Unlike metoclopramide or domperidone, L-646,462 also possessed a reasonably potent 5-HT receptor antagonist effect in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Inhibition of in vitro amine uptake into rat brain synaptosomes after in vivo administration of antidepressants.

The effects of in vivo administration of a number of antidepressants in doses up to 30 mg/kg i.p. on the in vitro uptake of 3H-amines were determined. The uptake of noradrenaline (NA) was competitively inhibited by 50% by desipramine, nomifensine and clomipramine. Dopamine uptake in the corpus striatum was inhibited by 50% by nomifensine. The uptake of 5-hydroxytryptamine (5-HT) was inhibited by clomipramine and fluoxetine. Iprindole and mianserin did not inhibit NA, DA or 5-HT uptake by more than 20%. The results demonstrate that the selectivities and potencies of antidepressants may be different in vivo to those in vitro. Thus, care should be taken when extrapolating to in vivo experiments, selectivities and potencies obtained in vitro.

Animals↗
PubMed1983

Involvement of 5-HT2 receptors in the wet-dog shake behaviour induced by 5-hydroxytryptophan in the rat.

The wet-dog shake behaviour induced by 5-hydroxytryptophan (5-HTP) was used as a model of central 5-hydroxytryptamine (5-HT) receptor activity in the rat. The wet-dog shake behaviour induced by 5-HTP was dose-dependent. Selective 5-HT2 receptor antagonists ketanserin, pirenperone and methysergide (with little selectivity) were administered to rats displaying the wet-dog shake behaviour. The three antagonists produced a rapid and dose-dependent inhibition of wet-dog shakes. Pirenperone was more potent than ketanserin, which was more potent than methysergide at inhibiting wet-dog shake behaviour. Since 5-HT2 receptor antagonists inhibit the 5-HTP-induced wet-dog shakes it is proposed that the wet-dog shakes induced by 5-HTP are mediated by activation of 5-HT2 receptors.

5-Hydroxytryptophan↗
PubMed1983

Pyridinylpiperazines, a new class of selective alpha 2-adrenoceptor antagonists.

A series of 1-(2-pyridinyl)piperazine derivatives was synthesized and evaluated for adrenergic activity. In vitro activity was assessed through the antagonism of clonidine's effect in the rat, isolated, field-stimulated vas deferens and by the displacement of [3H]clonidine from membrane binding sites of calf cerebral cortex. Antagonism of clonidine-induced mydriasis in the rat was used as an in vivo assay. Several members of the series proved to be potent, selective alpha 2-adrenoceptor antagonists. 1-(3-Fluoro-2-pyridinyl)piperazine was more potent than either yohimbine or rauwolscine in displacement of [3H]clonidine and had a higher affinity for this binding site (alpha 2) than for the [3H]prazosin site (alpha 1). In vivo, the 3-F derivative was more potent than the reference standards in reversing clonidine-induced mydriasis. None of the members of this series was more selective or potent than rauwolscine in antagonizing clonidine in the rat vas deferens.

Adrenergic alpha-Antagonists↗