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Biomedical subjects

S E Robinson

Publications and source records attributed to S E Robinson.

At least 91 records · Page 5Linked to original sources
PubMed1984

Cardiovascular effects of alpha-adrenergic agents in the dorsal raphe nucleus of the rat.

Local injection of norepinephrine (NE) or phenylephrine into the lateral aspect of the dorsal raphe nucleus results in an increase in blood pressure and heart rate in the urethane-anesthetized rat. The increases in blood pressure and heart rate are blocked by prior injection of phentolamine into the dorsal raphe nucleus and are significantly reduced by i.v. mecamylamine. Selective lesion of serotonergic neurons in the dorsal raphe nucleus by 5,7-dihydroxytryptamine significantly reduces the pressor response to phenylephrine, but does not affect the increase in heart rate in response to phenylephrine. These data are consistent with a central alpha-adrenergic mechanism in the dorsal raphe that elevates blood pressure at least partly by an action on serotonergic neurons and elevates heart rate by a mechanism involving non-serotonergic neurons in the dorsal raphe area.

Animals↗
PubMed1984

Serotonergic-cholinergic interactions in blood pressure control in the rat.

Both serotonergic and cholinergic mechanisms in the hypothalamus are involved in blood pressure control. Because lesion of the dorsal raphe or median raphe nucleus decreases the turnover of hypothalamic acetylcholine, interactions between serotonin and acetylcholine have been investigated in the hypothalamus with respect to blood pressure. Pharmacological manipulations that interfere with cholinergic neurotransmission in the posterior hypothalamus block the pressor response to serotonin in the anterior hypothalamic/preoptic area (AH/PO), reduce the pressor response to dorsal raphe stimulation, and have no effect on the pressor response to median raphe stimulation. Administration of the serotonin antagonist metergoline into the AH/PO blocks the pressor response to serotonin, slightly reduces the response to dorsal raphe stimulation, and does not affect the pressor response to median raphe stimulation. It is concluded that a hypothalamic cholinergic mechanism is needed to enable hypothalamic serotonergic neurons to elevate blood pressure. The dorsal raphe nucleus may be a source of these serotonergic terminals involved in this pressor response.

Acetylcholine↗
PubMed1983

Effect of specific serotonergic lesions on cholinergic neurons in the hippocampus, cortex and striatum.

Local injection of 5,7-dihydroxytryptamine into the median raphe nucleus of rats pretreated with desipramine decreases the serotonin content of the hippocampus and cortex. The turnover of acetylcholine, as measured by the rate of decline of acetylcholine content after hemicholinium-3, is not affected in the hippocampus or the striatum, but is increased in the cortex by such treatment. Local injection of 5,7-dihydroxytryptamine into the dorsal raphe nucleus of desipramine-treated rats decreases the serotonin content of the hippocampus, cortex, and striatum. The turnover of acetylcholine is increased in the hippocampus and cortex, but not affected in the striatum. Thus, serotonergic neurons from the median raphe nucleus appear to tonically inhibit cholinergic neurons in the cortex, and serotonergic neurons from the dorsal raphe nucleus appear to tonically inhibit cholinergic neurons in the hippocampus and cortex. These serotonergic neurons do not appear to act tonically on striatal cholinergic neurons.

5,6-Dihydroxytryptamine↗
PubMed1982

Interaction of the median raphe nucleus and hypothalamic serotonin with cholinergic agents and pressor responses in the rat.

Experiments were performed to determine whether the pathway by which median raphe stimulation increases blood pressore involves serotonergic terminals in the anterior hypothalamic/preoptic area and cholinergic terminals in the posterior hypothalamus. Injection of 5,7-dihydroxytryptamine into the median raphe nucleus decreases serotonin and turnover of acetylcholine in the hypothalamus of the rat. The hypertensive action of injection of serotonin into the anterior hypothalamic/preoptic area is blocked by injection of atropine or hemicholinium-3 into the posterior hypothalamus and by i.c.v. injection of hemicholinium-3 when measured in urethane-anesthetized rats. However, the pressor effect of electrical stimulation of the median raphe nucleus is not blocked by the intrahypothalamic injection of atropine or hemicholinium-3, only partially blocked by i.c.v. hemicholinium-3 and not blocked by specific lesioning with 5,7-dihydroxytryptamine. Moreover, injection of metergoline into the anterior hypothalamic/preoptic area blocks the pressur response to hypothalamic serotonin but does not block the pressor response to median raphe stimulation. Stimulation of the median raphe nucleus does not affect acetylcholine turnover in the hypothalamus. These results suggest that serotonergic mechanisms in the anterior hypothalamic/preoptic area exert their pressor effect through a pathway with a cholinergic link in the posterior hypothalamus. Serotonergic neurons arising in the median raphe nucleus probably are not involved in this pathway through the hypothalamus, although a cholinergic pathway may be involved elsewhere in their pressor actions. The effect of median raphe nucleus lesion on turnover of acetylcholine in the hypothalamus is most likely unrelated to regulation of blood pressure.

Acetylcholine↗
PubMed1981

Non-invasive magnetopneumographic determination of lung dust loads in steel arc welders.

Magnetopneumography was used to measure non-invasively the concentration of the ferrimagnetic fraction of retained welding fume in the thoraces of steel arc welders. This was done by measuring the remanent magnetic fields due to ferrimagnetic particles. The 11 welders studied had concentrations of thoracic ferrimagnetic mineral several orders of magnitude greater than three machinists, 16 former asbestos insulators and 24 control subjects. These concentrations correlated well with total years welding (p less than 0.01) and radiographic evidence of small rounded densities (p less than 0.05), but not with smoking history. There was a higher concentration of ferrimagnetic mineral over the hilar regions. Magnetopneumography offers a non-invasive indicator of the accumulation of welding fume in the thorax.

Adult↗
PubMed1980

Substance P in the superior cervical ganglion and the submaxillary gland of the rat.

Substance P has been detected in the superior cervical ganglion and submaxillary gland of the rat by radioimmunoassay. Decentralization, section of the carotid sinus nerve, or deefferentation does not affect the level of substance P in the rat superior cervical ganglion. Superior cervical ganglionectomy does not affect the amount of substance P in the submaxillary gland; however, section of the chorda tympani or duct ligation significantly reduces substance P in the submaxillary gland. It is concluded that substance P in the superior cervical ganglion is not located in the preganglionic sympathetic neurons, afferents from the glossopharyngeal nerve or post-ganglionic neurons projecting to the submaxillary gland or carotid body. Substance P does not appear to be associated with sympathetic innervation of the submaxillary gland, but it is anatomically and functionally related to the chorda tympani and possibly involved in the parasympathetic innervation of the gland. Substance P may also be present in gland cells of the submaxillary gland.

Animals↗
PubMed1980

Binding of reverse T3 to hepatic nuclear protein.

The study was undertaken to examine the potential intrinsic biological activity of reverse T3 by comparing its binding to nuclear protein in vitro with that of other iodothyronines. Nuclear protein was extracted from normal pig liver using methods described for rat tissues. At 25 degrees 30% of the added 125I rT3 was specifically bound to the nuclear protein. The order of potency in displacing 125I rT3 was rT3 > 3'5'T2 > T4 > T3 > 3,3'T2 > 3,5T2. This contrasted with the order of potency in displacing 125I T3 which was T3 > T4 > 3,3'T2 > 3,5T2 > rT3 > 3'5'T2. This difference in the hierarchy of iodothyronine binding is consistent with binding of these radioligands to different components of the nuclear protein extract. These experiments demonstrate separate binding components of nuclear protein for T3 and rT3 in a thyroid hormone responsive tissue and may be relevant to the mechanism of action of thyroid hormones.

Animals↗
PubMed1980

Binding of endogenous iodothyronines to isolated liver cell nuclei.

The metabolic role of a number of the metabolites of T4 is unknown. Hence, these iodothyronines, now known to be present in human serum, were tested for their ability to displace [125I]T3 from specific binding sites in isolated pig liver nuclei. Compared with T3 (1.0), the molar inhibition ratios of the analogs tested were: triiodothyroacetic acid, 4.4; T4 6.2; 3.3'-diiodothyronine, 56; 3,5-diiodothyronine, 245; rT3, 264; and 3',5'-diiodothyronine, 60,000. In isolated pig liver nuclei, the Ka for T3 was 1.73 +/- 0.21 X 10(9) M-1 and that for T4 was 0.17 +/- 0.06 X 10(9) M-1. Nuclei stored in liquid nitrogen for up to 8 weeks leaked bound [125I]T3 into the supernatant during the incubation period. No loss of bound [125I]T3 was observed with freshly prepared nuclei. The data indicate that, with the exception of T3 and T4, iodothyronines derived from T4 are unlikely to modulate the interaction of T3 with its receptor unless their perireceptor concentration is significantly greater than their serum concentration.

Animals↗
PubMed1980

Non-invasive magnetopneumographic estimation of lung dust loads and distribution in bituminous coal workers.

Magnetopneumography is a non-invasive technique for measuring the ferrimagnetic portion of retained dust in the lungs by means of its permanent magnetism. Magnetopneumography was used to measure the magnetic fraction of coal mine dust in 21 retired disabled bituminous coal miners and 14 active miners. Twenty rural subjects served as controls. The retired disabled miners had significantly higher levels of pulmonary ferrimagnetic mineral than the control subjects and most active miners (p < 0.001). Three of the active miners had significantly higher levels of ferrimagnetic mineral than did the other active miners and the control subjects (p < 0.005), yet could not be differentiated from other miners by work history or chest roentgenograms. This elevation could not be accounted for by sources other than coal mine dust. A pattern of central hilar concentration of ferrimagnetic mineral was noted in both retired and active miners. These results suggest that magnetopneumography is sufficiently sensitive to permit the non-invasive study of coal mine dust accumulation and distribution in the lung.

Adult↗
PubMed1979

Dopaminergic control of the septal-hippocampal cholinergic pathway.

Apomorphine given subcutaneously is known to decrease the turnover rate of acetylcholine (TR(ACh) in the hippocampus. Blockade of dopaminergic receptors by intraseptal haloperidol or destruction of dopaminergic terminals by intraseptal 6-hydroxydopamine results in an increase in TR(ACh) in the hippocampus. Specific destruction of the dopaminergic neurons projecting to the septum by the injection of 6-hydroxydopamine into the A10 mesencephalic cell group also results in an increased TR(ACh) in the hippocampus. None of the above treatments affects TR(ACh) in the cortex. Thus, it appears that dopaminergic neurons exert a tonic inhibitory effect on the ACh metabolism of the septal-hippocampal pathway, but do not affect that of cholinergic neurons projecting from the septum to the cortex. It can be inferred that this decrease in the rate of metabolism may be associated with a regulation of the rate of neuronal firing.

Acetylcholine↗
PubMed1978

Structural and steric requirements for beta-phenethylamines as agonists of the noradrenergic cyclic AMP generating system in the rat limbic forebrain.

The present studies were undertaken to assess the structural and steric requirements for beta-phenethylamines as agonists of the noradrenergic cyclic AMP generating system in slices of the rat limbic forebrain. Significant agonist activity of beta-phenethylamines requires a beta-3,4-dihydroxyphenethylamine with a beta-hydroxyl group in the R configuration. Thus, dopamine did not stimulate the system at concentrations up to 10(-3) M. Moreover, beta-hydroxyphenethylamines without a 3,4-catechol group (octopamine, phenylephrine, p-hydroxynorephedrine, metaraminol and methoxamine) - though exerting alpha-agonist activity in peripheral tissues - lack agonist activity in this particular cyclic AMP generating system. The effects of (R)-norepinephrine and (R)-isoproterenol at maximal concentrations were not additive. The results lend further support to the view that the cyclic AMP generating system in slices of the limbic forebrain is part of a norepinephrine receptor coupled adenylate cyclase system with a subpopulation of receptors that are beta in nature.

Animals↗
PubMed1975

On the significance of the increase in homovanillic acid (HVA) caused by antipsychotic drugs in corpus striatum and limbic forebrain.

The effect of various antipsychotic drugs on the blockade of dopaminergic receptors in striatum and limbic forebrain was examined by establishing dose-response curves for the increase in HVA and for the antagonism of d-amphetamine-induced rotation in rats with unilateral lesions of the substantia nigra. A good quantitative correlation was found between dopaminergic blockade in the striatum as reflected by the ED100 for striatal HVA increase and the ED50 for rotational antagonism and the occurrence of extrapyramidal side effects in man. The ED100 for the increase in HVA in the limbic forebrain showed the same rank order of potency as those in the striatum: Haloperidol greater than primozide greater than chlorpromazine greater than thioridazine greater than clozapine. The results thus demonstrate a very good correlation between the degree of dopaminergic blockade and the increase of extrapyramidal side effects in man, but suggest the possibility of a dissociation between dopaminergic blockade and antipsychotic activity.

Animals↗