Biomedical subjects

D R Wallace

Publications and source records attributed to D R Wallace.

At least 37 records · Page 2Linked to original sources

PubMed1990

Effect of age and monosodium-L-glutamate (MSG) treatment on neurotransmitter content in brain regions from male Fischer-344 rats.

Peripheral administration of monosodium-L-glutamate (MSG) has been found to be neurotoxic in neonatal rats. When administered in an acute, subconvulsive dose (500 mg/kg i.p.), MSG altered neurotransmitter content in discrete brain regions of adult (6 month old) and aged (24 month old) male Fischer-344 rats. Norepinephrine (NE) content was reduced in both the hypothalamus (16%) and cerebellum (11%) of adult rats, but was increased in both the hypothalamus (7%) and cerebellum (14%) of aged rats after MSG treatment. MSG also altered the dopamine content in adult rats in both the posterior cortex and the striatum, causing a reduction (23%) and an increase (12%), respectively. Glycine content in the midbrain of aged rats increased (21%) after MSG injection. Of particular interest is the widespread monoamine and amino acid deficits found in the aged rats in many of the brain regions examined. NE content was decreased (11%) in the cerebellum of aged rats. Dopamine content was reduced in both the posterior cortex (35%) and striatum (10%) of aged rats compared to adult animals. Cortical serotonergic deficits were present in aged rats with reductions in both the frontal (13%) and posterior cortex (21%). Aged rats also displayed deficits in amino acids, particularly the excitatory amino acids. There were glutamate deficits (9-18% reductions) in the cortical regions (posterior and frontal) as well as midbrain and brain stem. Aspartate, the other excitatory amino acid transmitter, was reduced 10% in the brainstem of aged rats. These data indicate that an acute, subconvulsive, dose of MSG may elicit neurochemical changes in both adult and aged male Fisher-344 rats, and that there are inherent age-related deficits in particular neurotransmitters in aged male Fisher-344 rats as indicated by the reductions in both monoamines and amino acids.

Aging↗

PubMed1990

Monoamine and amino acid content in brain regions of Brattleboro rats.

Monoamine and amino acid content were measured in brain regions from 12 week old male, homozygous Brattleboro (DI, n = 12) and Long-Evans control (LE, n = 12) rats. Norepinephrine (NE) content was significantly elevated (16-25%) in the spinal cord, pons-medulla and anterior hypothalamus of DI rats when compared to LE controls. NE content of the neurointermediate lobe of pituitary in DI rats was almost twice that of LE controls. Serotonin content was also significantly elevated in the spinal cord, pons-medulla, anterior hypothalamus and forebrain of DI rats relative to the LE controls. Taurine content in DI rats was increased (31-42%) above that of LE rats in the anterior hypothalamus, striatum and forebrain. Glutamine content was also greater in DI rats than LE in the spinal cord, pons-medulla, anterior hypothalamus, striatum, hippocampus and forebrain. The changes in monoamine and amino acid content were discussed in relation to the cardiovascular and osmoregulatory deficits that are present in DI rats due to arginine vasopressin (AVP) deficiency. The possible role of AVP in modulating NE turnover was also discussed. The increase in brain TAU content in DI rats may be a physiological response to hypernatremia.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1990

Neural-renal interactions in the hypertension induced by papillary necrosis: role of dietary salt intake.

The effects of high salt intake (1.0% NaCl in the drinking water) on rats made hypertensive by 2-bromoethylamine hydrobromide (BEA) treatment (200 mg/kg, i.p.) were examined. BEA-induced medullary necrosis resulted in a mild hypertension (146 +/- 5 mm Hg) that was exacerbated by 4 weeks of high salt intake (163 +/- 6 mmHg). BEA-treated rats had significant salt-induced increases in urinary norepinephrine excretion and hypothalamic and brainstem norepinephrine content, that were not present in BEA-treated rats drinking tap water or control rats drinking saline. BEA treatment in combination with increased salt intake produced a decrease (p less than 0.05) in renal dopamine content and adrenal norepinephrine stores relative to BEA treatment alone. BEA treatment also significantly decreased renal norepinephrine stores and dopamine binding sites irrespective of salt intake. Renal alpha 2-adrenergic receptors and central nervous system stores of dopamine and serotonin were unaffected by BEA treatment. Renal function was well preserved as indicated by normal creatinine, glucose and protein excretion; however, significant (p less than 0.05) disruption of the urinary concentrating mechanism was present. These studies suggest that BEA-induced hypertension has a neural component that is exacerbated by high salt intake. The primary defect in BEA hypertension appears to be the lack of circulating antihypertensive lipids that attenuate the ability of salt loads to simulate sympathetic nervous system activity.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1990

Decreased plasma taurine in aged rats.

Taurine (TAU) is thought to be a neuromodulator or an inhibitory neurotransmitter in the mammalian brain. In the periphery, TAU is involved in a wide spectrum of physiological functions. One of the most important putative physiological function of TAU is the modulation of cardiovascular activity including blood pressure control. TAU also appears to be important for the development of an organism, especially early central nervous system development. Regional TAU content was measured in brains of adult (6-month) and aged (23- to 26-month) Fischer-344 (F-344) male rats. To assess the putative neurotransmitter role of TAU, release due to potassium depolarization was studied using slices from frontal cortex of F-344 rats. Circulating levels of TAU were also determined in male F-344 rats (6 and 24 months of age) and female Long-Evans rats (LE, 6 and 30 months old). We found no age-related change in TAU stores from the brain regions examined, nor did we find any indication of TAU release due to potassium depolarization in the release paradigm utilized. There was, however, a significant reduction (28 and 42%) in plasma TAU concentration in F-344 and LE rats, respectively. This age-related reduction in plasma TAU may have important consequences both peripherally and centrally with respect to regulation of blood pressure, cardiovascular function, and cardioprotection, as well as possible CNS complications.

Aging↗

PubMed1989

A pharmacological analysis of food intake regulation in rats treated neonatally with monosodium L-glutamate (MSG).

Studies were conducted to examine deficits in food intake regulation in MSG-treated rats that result from known or suspected damage to neurotransmitter systems involved in feeding. Male rats were injected with either MSG (4 mg/g) or sodium chloride on postnatal days 2 and 4 (MSG-Lo) or postnatal days 2, 4, 6 and 8 (MSG-Hi). As adults, MSG-treated and control rats (n = 12/group) were examined for deficits in pharmacologically elicited feeding and other measures of food intake regulation. A second group of MSG-treated (n = 9/group) and control rats (n = 12) were used to measure basal blood pressure and nociceptive reactivity in adulthood. Organ weights, body weight and neuropeptide Y (NPY) content in brain regions were determined at the end of the study. MSG-Hi rats consumed significantly less food than controls during the dark part of the light cycle. Both MSG-Hi and MSG-Lo groups ate significantly less food than controls after a 48-hour fast. MSG-Hi and MSG-Lo rats consumed significantly less food than controls in response to 1.0 mg/kg morphine. MSG-Hi rats consumed significantly less food than controls during the dark phase and significantly more food than controls during the light phase in response to naloxone (1.0 mg/kg). MSG-Lo ate significantly more than controls in response to 0.1 mg/kg guanfacine. MSG-Hi and MSG-Lo showed a significant attenuation in diazepam-stimulated feeding when compared to controls. Blood pressure was significantly lower in both MSG-Hi and MSG-Lo rats compared to controls. Tail flick latencies were not altered by MSG-treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Basic fibroblast growth factor stimulates the growth and inhibits casein accumulation in mouse mammary epithelial cells in vitro.

The effects of basic fibroblast growth factor (bFGF) on the growth and differentiation of mouse mammary epithelial cells in serum-free collagen gel culture were examined. Epithelial cells obtained from virgin or midpregnant mice grew when bFGF was added to medium containing either insulin at a concentration greater than or equal to 1 microgram/ml or somatomedin-C (Sm-C) at 150 ng/ml. This growth-promoting effect is of the same magnitude as, and additive with, the growth-promoting effect of epidermal growth factor (EGF) or mammogenic hormones. The sensitivity of the cells to EGF or mammogenic hormones was not altered by exposure to bFGF. The progeny cells resulting from growth stimulation by bFGF are capable of accumulating casein upon subsequent stimulation by prolactin (PRL), but accumulate less casein than cells grown in response to EGF. bFGF also appears to reduce casein accumulation if it is added to the cultures at the same time as PRL.

Animals↗

PubMed1989

Central and peripheral actions of alpha 2-adrenergic agonists on renal function in Long-Evans and Brattleboro rats.

The effects of 3 alpha 2-adrenergic receptor agonists on renal function in vasopressin (AVP)-deficient Brattleboro (DI) rats were evaluated. The aim of this study was to determine the relative contribution of central versus peripheral alpha 2-adrenoceptors in mediating diuresis and natriuresis, as well as the role of alpha 2-adrenoceptors in antagonizing the actions of AVP. In addition to the studies of renal function, the effects of AVP deficiency on renal alpha 2-adrenoceptor affinity and number was evalauted along with determination of peripheral catecholamine stores. The centrally acting alpha 2-adrenergic agonists guanabenz and guanfacine significantly increased urine output and sodium excretion in Long-Evans (LE) rats. Guanabenz and guanfacine increased urine output in DI rats but failed to increase sodium excretion. The polar alpha 2-adrenergic agonist, ST-91, increased sodium excretion in both LE and DI rats, however, at a dose of 1.0 mg/kg urine output was significantly decreased in DI rats. The 3 alpha 2-adrenergic agonists increased potassium excretion in LE rats, but at the 1.0-mg/kg dose of guanabenz and ST-91, potassium excretion was significantly inhibited in DI rats. Renal alpha 2-adrenergic receptors and norepinephrine stores were not altered in DI rats. Adrenal NE stores were significantly elevated in DI rats relative to LE rats. The results of this study suggest that in the absence of AVP, centrally acting alpha 2-adrenergic agonists have limited natriuretic action, although peripheral activation of alpha 2-adrenoceptors is sufficient to elicit natriuresis irrespective of the presence of AVP. The chronic deficiency of AVP does not alter renal alpha 2-adrenergic receptor number, but the natriuretic and kaliuretic actions of alpha 2-adrenergic agonists are altered in DI rats.

Adrenergic alpha-Agonists↗

PubMed1988

Proliferative effects of insulin and epidermal growth factor on mouse mammary epithelial cells in primary culture. Enhancement by hydroxyeicosatetraenoic acids and synergism with prostaglandin E2.

Linoleate metabolism via the cyclooxygenase pathway enhances the proliferation of mammary epithelial cells in serum-free culture in the presence of epidermal growth factor and insulin (Bandyopadhyay, G.K., Imagawa, W., Wallace, D., and Nandi, S. (1987) J. Biol. Chem. 262, 2750-2756). Prostaglandin E2 (PGE2) can fully substitute for linoleic acid provided endogenous hydroxyeicosatetraenoic acids (HETEs, lipoxygenase metabolites) are available. The PGE2 effect is partial if lipoxygenase activity is inhibited by nordihydroguaiaretic acid. Any combination of two HETEs out of three tested (5-, 12-, and 15-HETEs) stimulates growth synergistically with PGE2; and together (i.e. PGE2 + HETEs), they completely substitute for linoleate. In the absence of PGE2, maximal stimulation cannot be attained with HETEs. Exogenous 5-HETE, compared with 12- or 15-HETE, is preferentially incorporated by the mammary epithelial cells, and about 25-30% of it is retained esterified in phospholipids. The cellular level of nonesterified, free HETE is low. Radioimmunoassay revealed that the concentrations of 12- and 15-HETEs in the culture media (with or without added linoleate) were always higher than that of 5-HETE. Both intra- and extracellular free HETEs are rapidly metabolized by the cells. Since these cells are capable of producing eicosanoids from linoleate, periodic supplementation of the cultures with linoleate allows maintenance of higher HETE and PGE2 levels. Thus, it appears that not only are HETEs short-lived in the cell cultures, but cells handle 5-HETE differently than 12- and 15-HETEs. Whatever may be the pathways of interaction, synergism between HETEs and PGE2 seems to explain how linoleate stimulates the growth of mammary epithelial cells in the presence of epidermal growth factor and insulin.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed1985