Biomedical subjects

T A Reader

Publications and source records attributed to T A Reader.

At least 127 records · Page 7Linked to original sources

PubMed1980

Monoaminergic denervation of the rat hippocampus: microiontophoretic studies on pre- and postsynaptic supersensitivity to norepinephrine and serotonin.

The responsiveness of hippocampal CA3 pyramidal neurons to microiontophoretic applications of serotonin (5-HT), norepinephrine (NE), gamma-aminobutyric acid (GABA) and isoproterenol (ISO) was assessed in rats following 5,7-dihydroxy-tryptamine (5,7-DHT) and 6-hydroxydopamine (6-OHDA) pretreatments and bilateral locus coeruleus lesions. The intraventricular administration of 200 micrograms (free base) of 5,7-DHT and of 6-OHDA produced 89% and 93% decreases of 5-HT and NE respectively. None of these pretreatments modified the inital responsiveness to, or recovery from iontophoretic application of 5-HT. In 6-OHDA pretreated and locus-lesioned rats, the initial effectiveness of NE was not altered but its effect was markedly prolonged. However, there was no such prolongation of the effect of ISO which is not a substrate for the high affinity NE reuptake. The effect of GABA was not affected by these pretreatments. Acute pharmacological blockade of the NE reuptake with desipramine (5 mg/kg, i.p.) similarly induced a prolongation of the effect of iontophoretically applied NE, while fluoxetine (10 mg/kg, i.p.) a 5-HT reuptake blocker, failed to alter the recovery of pyramidal cells from iontophoretic application of 5-HT. It is concluded that 5-HT denervation induces neither pre- nor postsynaptic types of supersensitivity in hippocampal pyramidal cells, contrasting with the previously shown supersensitivity of ventral lateral geniculate and amygdaloid neurons following 5-HT denervation. NE denervation fails to induce a postsynaptic type of supersensitivity but leads to a marked prolongation of the response to NE indicative of a presynaptic mechanism. These results underscore the necessity for regional studies of neurotransmitters and drug action.

Animals↗

PubMed1980

Microiontophoresis of biogenic amines on cortical neurons: amounts of NA, DA and 5-HT ejected, compared with tissue content.

The present series of studies were carried out to quantify the amounts of dopamine (DA), noradrenaline (NA) and serotonin (5-HT) ejected from iontophoresis micropipettes and that produce inhibitory and modulatory effects on cortical neurons, in the frontoparietal cortex of the rat and in the occipital cortex of the cat. Using radioactive isotopes of the biogenic amines the effective transport number (n) was found to be 0.08 for DA; 0.13 for NA, and 0.22 for 5-HT. In addition, similar determinations were made, for comparison purposes, of the transport numbers of the neurotransmitters acetylcholine (ACh; n = 0.44), gamma-amino-n-butyrate (GABA, n = 13), and glutamate (GLU; n = 0.27). The quantities ejected under in vivo conditions were then estimated using Faraday's formula and fell in the pmol range (10(-12) mol). The effects of DA, NA and 5-HT on cortical units were studied; the amounts ejected were compared with the endogenous tissue content of these amines, determined by means of specific and sensitive radioenzymatic assays in the regions where the microiontophoretic experiments were performed. These results are discussed in the light of the anatomical, biochemical and electrophysiological data suggesting a modulatory role for the biogenic amines in the cerebral neocortex.

Acetylcholine↗

PubMed1979

The intracortical distribution of norepinephrine, dopamine and serotonin in the cerebral cortex of the cat.

The intracortical distribution of the biogenic amines (BA), norepinephrine (NE), dopamine (DA) and serotonin (5-HT), was determined for the parietal and occipital cortical areas of the cat. Under microscopic control, slices of each region were dissected out into 4 fractions: (1) an upper gray fraction (G1); (2) a medium gray fraction (G2); (3) a lower gray fraction (G3) and (4) a white-matter fraction (W). The BA were assayed by means of specific and sensitive radioenzymatic techniques; using catechol-O-methyltransferase (COMT) for the catecholamines (CA), and N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) for the 5-HT. In the two cortical regions studied, NE and DA were found to be distributed in an orderly laminar fashion. The highest levels of endogenous CA were measured in the superficial layers (fractions G1 and G2) while the white matter (fraction W) exhibited the lowest content of both NE and DA. DA represented 32--38% of the total CA content of the parietal cortex and 32--41% of the total CA content in the occipital cortex. In the parietal cortex, the distribution of 5-HT was similar in pattern to that of the CA, i.e., a decreasing concentration gradient with the highest endogenous levels in the G1 fraction and the lowest content in the W fraction. In the occipital cortex, the distribution was also found to be laminar for the gray matter but the W fraction showed a higher endogenous content than the lower gray fraction (G3). The release of NE, DA and 5-HT was studied by means of cortical superfusion in an in vivo preparation. The concentrations of BA measured in 30 min interval superfusates was fairly constant in a given experiment under basal conditions but varied widely from experiment to experiment. Variations in the basal overflow of NE were often independent of those found for DA and the basal overflow of 5-HT seemed independent of those of CA. The laminar intracortical distribution of endogenous NE, DA and 5-HT in cerebral cortex demonstrated by microdissection and biochemical assay techniques suggests a definite and structured pattern of aminergic innervation. Furthermore, the fact that these BA are released and a basal overflow can be detected and measured appears compatible with significant roles of NE, DA and 5-HT in synaptic transmission in the cerebral cortex.

Acetylserotonin O-Methyltransferase↗

PubMed1979

Modulatory role for biogenic amines in the cerebral cortex. Microiontophoretic studies.

In order to investigate the mode of action of biogenic amines in rat cerebral cortex, the unitary activity of spontaneously firing neurons and their excitatory response to acetylcholine (ACh) were examined using microiontophoretic administration of dopamine (DA), noradrenaline (NA) and serotonin (5-HT). The predominant effect of these biogenic amines on the spontaneous activity was a profound and prolonged inhibition of firing (2-4 min), which attained its maximum within 15-120 sec. This response was generally more abrupt in onset and of greater magnitude with NA and 5-HT than with DA. Most units inhibited by DA, NA and 5-HT also showed marked depression of their excitatory response to ACh when pretreated with these biogenic amines. With repetitive administration of ACh, it could be shown that the total duration of inhibition of ACh responses by DA and NA was not as prolonged as the inhibition of the spontaneous firing of the same cells. With 5-HT, the initial ACh responses of many neurons could be completely blocked, and this inhibitory effect lasted as long as the inhibition of spontaneous firing. In view of the anatomical data demonstrating a relative sparsity of monoamine nerve terminals in cerebral cortex, the strong inhibition induced by DA, NA or 5-HT may have reflected slow inactivation of the biogenic amines. However, it could also be indicative of underlying mechanisms of action dependent on metabolic changes. Indeed, the interaction between biogenic amines and ACh might imply a balance between the intracellular pools of cAMP and cGMP is directly or indirectly influenced by the biogenic amines and ACh, respectively. This hypothesis would not exclude other modes of local interaction between DA, NA, 5-HT and ACh, and appears compatible with the modulatory role of biogenic amines in cerebral cortex.

Acetylcholine↗

PubMed1978

The effects of dopamine, noradrenaline and serotonin in the visual cortex of the cat.

The predominant effect of dopamine, norepinephrine and serotonin on the photically-evoked urinary activity was a prolonged inhibition of firing. These amines were also able to block acetylcholine-induced excitations and for longer periods of time than GABA.

Acetylcholine↗

PubMed1976

Studies on the ultrastructure, histochemistry and cytochemistry of the uninfected digestive gland of Bithynia tentaculata (Mollusca: Gastropoda) and on the ultrastructure of this host organ in snails infected with larval digeneans.

The structure and function of the digestive gland of the gastropod mollusc, Bithynia tentaculata, was investigated using ultrastructural, histochemical, and cytochemical techniques. The digestive gland was shown to be composed of two main cell types, the "digestive" cells and "secretory" cells. The digestive cells appeared to be concerned with the absorption and digestion of nutrients, while secretory cells produced digestive enzymes and calcareous concretions. Undifferentiated cells were scattered between these two main cell types. The pathological effects of larval digeneans on the digestive gland were also investigated, at the ultrastructural level. In such infected snails the digestive gland appeared to be degenerating. The significance of this tissue destruction was briefly discussed.

Acid Phosphatase↗

PubMed1976

Catecholamines released from cerebral cortex in the cat; decrease during sensory stimulation.

In an attempt to determine the functional role of catecholamine (CA) nerve terminals in cerebral cortex the release of endogenous norepinephrine (NE) and dopamine (DA) into superfusates from visual and somatosensory cortex of the cat have been measured by a sensitive radiometric enzymatic assay based on the methylation of CA by catechol-O-methyltransferase (COMT) in the presence of a [3H]-methyl donor and followed by resolution of 3H derivatives through a series of organic extractions. In the flaxedilized animal maintained under local anaesthesia with artificial respiration the concentration of CA measured in 30-min superfusates was fairly constant in a given experiment under basal conditions without sensory stimulation, but varied widely from one experiment to another. Variations in NE were often independent of those for DA. For visual cortex the average basal release of NE in experiments was 20.09 +/- 3.64 pg/min/sq.cm while the average for DA was 34.01 +/- 7.62 pg/min/sq.cm. In all experiments intermittent visual stimulation (15/sec) produced a significant reduction in release rate averaging about 42% for NE and 64% for DA in visual cortex. The reduction was relatively non-specific since visual or somatic sensory stimulation produced a decrease in release from both visual and somatic sensory cortical areas. Since it has been shown that there is a relatively non-specific increase in acetylcholine (ACh) release from sensory cortex during stimulation, it is proposed that ACh may regulate CA release at presynaptic CA terminals in the cortex as it does in the periphery. A marked increase in CA release observed on perfusing with nicotine or atropine is consistent with this hypothesis.

Acetylcholine↗

PubMed1976

The incorporation of hydrophobic protein receptors and artificial lipid membranes.

The mechanism of chemical synaptic transmission implies: 1) the existence of a specific protein receptor at the postsynaptic membrane, and 2) the interaction between the transmitter released and the receptor, thus producing a change in ionic permeability. Previous studies from our laboratory have shown that special hydrophobic proteins extracted from postsynpatic membranes of different tissues showed a high affinity binding for the different pharmacological agents. The present paper describes experiments in which different hydrophobic protein binding acetylcholine, noradrenaline, gamma-aminobutyric acid, and glutamate were incorporated into artificial lipid membranes, similar to those first described by Mueller et al. (19). The effect of the different pharmacological agents was tested under experimental conditions of voltage clamp and the d.c. current changes measured. The results were then compared for the different lipid-protein membranes employed during the steady state and during transient conductance changes. The specificity of the responses indicate that artificial lipid membranes containing these hydrophobic proteins from electroplax, myocardium, spleen capsule and shrimp muscle can be used as a model to study pharmacologic receptors.

Acetylcholine↗

PubMed1974