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Biomedical subjects

L L Ross

Publications and source records attributed to L L Ross.

At least 37 records · Page 2Linked to original sources
PubMed1987

Regulation of adrenal chromaffin cell development by the central monoaminergic system: differential control of norepinephrine and epinephrine levels and secretory responses.

In the mature rat, reflex sympathetic stimulation by insulin-induced hypoglycemia resulted in profound depletion of adrenal epinephrine, and to a lesser extent, norepinephrine. In the developing rat, insulin evoked little or no secretory response from the adrenals prior to 1 week of age. By 7 days, a moderate depletion of epinephrine was seen and the magnitude of the response increased with age. In contrast, during the first 3 weeks of postnatal life, insulin failed to deplete norepinephrine from the adrenal medulla and in fact, produced an increase. This chiefly resulted from de novo biosynthesis of the amine, as the rise was blocked by alpha-methyl-p-tyrosine. These results suggest that the ontogeny of the two chromaffin cell types (norepinephrine and epinephrine-containing) in the adrenals and the maturation of their secretory responses are under differential regulation. Because descending supraspinal catecholaminergic and serotonergic systems have been implicated to play key roles in regulating adrenomedullary function, the ontogeny of the sympatho-adrenomedullary axis was evaluated after neonatal central lesioning with 6-hydroxydopamine or 5,7-dihydroxytryptamine. 6-Hydroxydopamine resulted in a preferential elevation of epinephrine in the developing adrenals as well as an increase in the responsiveness of the adrenals to reflex stimulation by insulin; the mature secretory pattern was obtained as early as at 4 days postnatally for epinephrine and 9 days for norepinephrine. In contrast, 5,7-dihydroxytryptamine led to a preferential reduction of basal adrenal norepinephrine content.(ABSTRACT TRUNCATED AT 250 WORDS)

5,7-Dihydroxytryptamine↗
PubMed1985

Development of serotonergic and adrenergic receptors in the rat spinal cord: effects of neonatal chemical lesions and hyperthyroidism.

The sympathetic preganglionic neurons in the spinal cord receive dense serotonergic (5-HT) and catecholaminergic (CA) afferent inputs from the descending supraspinal pathways. In the rat spinal cord, the levels of these biogenic amines and their receptors are low at birth, but undergo rapid ontogenetic increases in the ensuing 2-3 postnatal weeks until the adult levels are reached. In many systems it has been shown that denervation of presynaptic neurons leads to an up-regulation of the number of postsynaptic receptors. To determine whether the 5-HT and CA receptors in the developing spinal cord are also subject to such transsynaptic regulation, we examined the ontogeny of serotonergic receptors and alpha- and beta-adrenergic receptors in thoracolumbar spinal cord of rats given neurotoxins which destroy serotonergic (5,7-dihydroxytryptamine (5,7-DHT)) or noradrenergic (6-hydroxydopamine (6-OHDA)) nerve terminals. Intracisternal administration of 5,7-DHT or 6-OHDA at 1 and 6 days of age prevented, respectively, the development of 5-HT and CA levels in the spinal cord. Rats lesioned with 5,7-DHT displayed a marked elevation of 5-HT receptors with a binding of 50% greater than controls at 1 week and a continuing increase to twice normal by 4 weeks. A similar pattern of up-regulation was also detected with the alpha-adrenergic receptor, as rats lesioned with 6-OHDA exhibited persistent increases in receptor concentration. However, in these same animals ontogeny of the beta-adrenergic receptor in the spinal cord remained virtually unaffected by the chemical lesion. In several other parts of the nervous system, it has been demonstrated that the beta-adrenergic sensitivity can be modulated by hormonal signals, particularly that of the thyroid hormones. This phenomenon was examined in the spinal cord and in confirmation with previous studies neonatal treatment of triiodothyronine (0.1 mg/kg, s.c. daily) was capable of evoking persistent increases in beta-adrenergic receptor binding. These results suggest that: (a) development of the postjunctional serotonergic and alpha-adrenergic receptors in the rat spinal cord can occur in the absence of the prejunctional nerve terminals and are subject to transsynaptic modulation; (b) beta-adrenergic receptors in the spinal cord also can develop after prejunctional lesions but are regulated by hormonal rather than neuronal factors.

Animals↗
PubMed1983

An epinephrine-containing pathway in avian spinal cord: development and localization.

We have studied the uptake mechanism, biochemistry and autoradiographic localization of a descending epinephrine-containing pathway in the chick spinal cord. This epinephrine (E) projection has a developmental timetable (appears at 14 days in ovo) that is different from those of the serotonin (5-HT) and norepinephrine (NE) projections which appear at 8 and 12 days respectively. E possesses its own uptake mechanism with different pharmacological specificities from those of the NE and 5-HT uptake mechanisms. Phenylethanolamine-N-methyltransferase (PNMT), the enzyme that converts NE to E, is present in the cord at 14 days in ovo which is the same time that the uptake mechanism is detectable. Transection of the spinal cord at upper thoracic levels almost completely eliminates the uptake mechanism and PNMT activity below the transection, indicating a supraspinal origin of this pathway. E can first be detected fluorimetrically at 12 days in ovo but at this age E appears not to be of supraspinal origin since transmission at 5 days in ovo does not deplete the spinal cord of E. However, transection of the spinal cord at 3 days post-hatching does markedly reduce the E content by 12 days. Autoradiographic analysis after uptake with [3H]E shows a circumscribed localization of the uptake of E to the neuropil of the preganglionic sympathetic nucleus (nucleus of Terni). These observations demonstrate the presence of a separate descending epinephrine-containing projection in the avian spinal cord which terminates predominantly on preganglionic sympathetic neurons. This pathway may be the major central autonomic pathway in the avian spinal cord.

Aging↗
PubMed1980

Localization of noradrenergic terminals in sympathetic preganglionic nuclei of the rat: demonstration by immunocytochemical localization of dopamine-beta-hydroxylase.

The noradrenergic (NE) innervation to sympathetic preganglionic nuclei in the rat thoracic cord was studied by immunocytochemical localization of dopamine-beta-hydroxylase (DBH), a specific NE antigen. DBH antisera was prepared against DBH purified from bovine adrenal medulla. The most intense immunoreaction was observed within the intermediolateral cell column (IML) of the spinal cord, the major sympathetic preganglionic nucleus in mammals. DBH was also localized in both the central autonomic and intercalated nuclei, cell groups known to contain sympathetic preganglionic visceral motor neurons. Two weeks following a midthoracic spinal transection, DBH immunoreactivity was no longer observed caudal to the lesion. Thus, the cells of origin of these noradrenergic terminals are supraspinal. Following a midthoracic hemisection DBH, immunoreactivity was similarly reduced in both the ipsilateral and contralateral IML caudal to the lesion. Therefore, bulbospinal NE neurons project bilaterally to sympathetic preganglionic nuclei.

Animals↗
PubMed1976

Separately developing axonal uptake of 5-hydroxytryptamine and norepinephrine in the fetal ileum of the rabbit.

Uptake of 5-hydroxytryptamine (5-HT) by adult and fetal rabbit's ileum was studied. The adult myenteric plexus accumulated tritium when incubated with tritiated 5-HT. However, in addition to labeled 5-HT, tritiated 5-hydroxyindole acetic acid and, when monoamine oxidase (MAO) was inhibited, 5-HT-o-glucuronide were found in the tissue. Two uptake processes differing in affinity could be defined. Only the high affinity process was saturable. Fetal ileum took up tritiated 5-HT but glucuronidation did not occur when MAO was inhibited. The uptake of tritiated 5-HT by the fetal ileum was due to a single, saturable, temperature sensitive (Q10 at 27-37 degress C = 2.4) process inhibited by ouabain. It was identical to the high affinity uptake found in adult tissue. This specific high affinity uptake could be found as early as the 16th day of gestation, 5-8 days before uptake of norepinephrine (NE) begins. Light and electron microscope radioautography revealed that the uptake of 5-HT was primarily into axons and a characteristic structure called the expanded process, both in the myenteric plexus. Both contained dense-cored vesicles. Axons were not labeled by tritiated NE until after 24 days and the expanded process was never labeled by tritiated NE. This study shows that uptake of 5-HT is a property of distinct system of axons in the mammalian myenteric plexus which develops prior to adrenergic axons during ontogeny.

Animals↗
PubMed1976

Serotonin accumulation in the guinea-pig myenteric plexus: ion dependence, structure-activity relationship and the effect of drugs.

The specific accumulation of serotonin in neurons of the guinea-pig myenteric plexus was examined. Nonadrenergic neurons have been shown to be responsible for this accumulation. Serotonin accumulation, known to be sodium-dependent, was found to be inhibited by elevating the external potassium concentration. Accumulation was inversely related to the concentration of potassium and was also decreased in the presence of 0 mM Ca++ or 12 mM Ca++. The affinity of analogous molecules for the myenteric plexus was greatly reduced in compounds which had no alkyl amino side chain, in which the amino group was methylated or which had no 5-hydroxyl group. Most analogs competitively inhibited serotonin accumulation and 6-hydroxytryptamine was demonstrated by histofluorescence to be taken up into the myenteric plexus after chemical sympathectomy with 6-hydroxydopamine. Serotonin accumulation was also inhibited by tricyclic antidepressants and amphetamines. The inhibition of serotonin accumulation by these compounds differed from their inhibition of accumulation of norepinephrine. As in the central nervous system, chlorimipramine was the most potent tricyclic antidepressant against accumulation of serotonin while desmethylimipramine was the most potent inhibitor of the accumulation of norepinephrine. Amphetamines were more effective inhibitors of serotonin accumulation than were tricyclic antidepressants, but all of these drugs were more effective against the accumulation of norepinephrine than serotonin. This study confirms the existence of a unique population of axons int he mammalian myenteric plexus which are distinguishable by their characteristic accumulation of serotonin and have not been found elsewhere in the peripheral nervous system.

Amphetamines↗
PubMed1973

The -glutamyl cycle in the choroid plexus: its possible function in amino acid transport.

Various anatomic regions of rabbit brain have been examined for activities of the enzymes of the gamma-glutamyl cycle. While these enzyme activities were widely distributed in the brain, they are present in much higher concentrations in the choroid plexus than in other parts of the brain. The activities observed are of about the same order of magnitude as found in the kidney. These observations and other considerations suggest that the gamma-glutamyl cycle may play a significant role in the transport of amino acids between blood and cerebrospinal fluid.

Acyltransferases↗
PubMed1973

Enzymes of the gamma-glutamyl cycle in the ciliary body and lens.

The enzymes of the gamma-glutamyl cycle have been found in rabbit ciliary body and, except for 5-oxoprolinase, also in the ocular lens. Histochemical studies show that gamma-glutamyl transpeptidase is localized mainly in the basal portions of the epithelial cells of the ciliary body; the findings are similar to those observed in the chloroid plexuses. The histochemical staining reaction in the ciliary epithelium is more intense than in the chloroid plexus, intestine, and kidney. gamma-Glutamyl transpeptidase staining activity in the epithelium of the intestinal and renal proximal convoluted tubules is confined to the microvillus border. Moderate transpeptidase activity was found in the cytoplasm of nonpigmented epithelial cells of the iris at the posterior pupillary margin. The histochemical and enzyme activity studies are consistent with the thesis that the gamma-glutamyl cycle functions in transport of amino acids across the blood-aqueous humor barrier.

Acyltransferases↗
PubMed1971

Electron microscope radioautographic identification of serotonin-synthesizing cells in the mouse gastric mucosa.

This study correlates the fine structure of mouse gastric endocrine cells with their ability to synthesize serotonin (5-HT) from 5-hydroxytryptophan (5-HTP). Mice were sacrificed 2 hr after the intravenous injection of 5-HTP-(3)H or 5-HT-(3)H. Their stomachs were processed for light- and electron microscope radioautography in a manner which retained labeled 5-HT while washing out other labeled substances. Stomachs from additional mice were incubated in vitro with 5-HT-(3)H and processed similarly. All morphologic types of mouse gastric endocrine cells exhibited a similar facility to incorporate exogenous 5-HTP and to convert it to 5-HT which was bound intracellularly. Differences in densities of silver grains observed over endocrine cells suggested that individual endocrine cells indeed varied in their ability to synthesize and/or to bind 5-HT; such variations, however, were not reflected by differences in fine structure, with the exception that endocrine cells with few granules always contained little newly synthesized 5-HT. The newly synthesized 5-HT was associated with the intracellular granules. The gastric endocrine cells were not labeled by exogenous 5-HT-(3)H, whereas mast cells were labeled by either 5-HT-(3)H or 5-HTP-(3)H administration. The findings of the present study support the position that the gastric endocrine cells represent a single cell type, at least in respect to serotonin metabolism-that the argyrophil or argentaffin reactivity of these cells merely reflects their amine content at a given time.

5-Hydroxytryptophan↗