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Biomedical subjects

R L Hawkins

Publications and source records attributed to R L Hawkins.

At least 37 records · Page 2Linked to original sources
PubMed1984

The effects of insulin and glucagon on ketone-body turnover.

A double-isotope procedure was used to measure the effects of insulin and glucagon on ketone-body production and utilization (i.e. turnover) in the starved rat. Somatostatin was infused during the experiment to suppress the pancreatic release of either hormone. The immediate action of insulin in terms of ketone-body turnover that was most evident was a decreased production of 3-hydroxybutyrate, with no significant change in the turnover of acetoacetate. Similarly, the significant effect of glucagon infusion was to increase the production of 3-hydroxybutyrate, with minimum increase in acetoacetate turnover. The data support a direct effect of both hormones on the distribution of acetyl units derived from fatty acid beta-oxidation.

3-Hydroxybutyric Acid↗
PubMed1984

A double-isotope method for the measurement of ketone-body turnover in the rat. Effect of L-alanine.

The synthesis of 4-3H-labelled ketone bodies, and their use along with 14C-labelled ketone-body precursors, is employed using an 'in vivo' rat infusion model to measure ketone-body turnover. The use of two isotopes is necessary to measure ketone-body turnover when ketogenesis may occur from more than one precursor such as glucose and fatty or amino acids. Requirements of isotopic equivalence in terms of metabolic similarity, valid stoichiometry and the lack of differences in the kinetics of relevant enzymes is demonstrated for the 4-3H- and 14C-labelled ketone bodies. The hypoketonaemic effect of L-alanine is shown by two distinct phases after the administration of L-alanine. During the first 12 min after alanine administration ther was a 50% decrease in acetoacetate and a 30% decrease in 3-hydroxybutyrate production, with no significant change in the utilization of either compound. The hypoketonaemic action of alanine during the following 16 min was primarily associated with an uptake of 3-hydroxybutyrate that was somewhat greater than the increase in its production. There were essentially equivalent decreases in production and utilization of acetoacetate, resulting in no significant net change in the level of this ketone body in the blood.

3-Hydroxybutyric Acid↗
PubMed1984

Neurochemical changes in murine trisomy 16: delay in cholinergic and catecholaminergic systems.

Two strains of Mus musculus musculus, C57BL/6J and CD-1, and Mus musculus poschiavinus, the tobacco mouse, were used to study the effects of increased gene dosage of mouse chromosome 16 (MMU 16). A developmental delay has been found in the brains of murine trisomy 16 (Ts16) fetuses. Both the brain weight (in all three strains) and DNA content (in CD-1) were reduced, while protein content was unchanged in Ts16 compared to normal littermates. The daily increments of weight and protein (except in M. m. poschiavinus) were significantly greater in Ts16. The activities of choline acetyltransferase and acetylcholinesterase and muscarinic receptor binding were reduced. Their daily increments were also reduced to less than 56% that of littermates in Ts16 brains. The rate limiting enzymes of catecholaminergic neurons, tyrosine hydroxylase and dopamine beta-hydroxylase, and the concentration of catecholamines in the brains of Ts16 animals were lower. The activities of three other catecholaminergic enzymes, DOPA decarboxylase, catechol O-methyltransferase, and monoamine oxidase, were generally elevated in Ts16 brain, as were their daily increments. These observations indicate a significant developmental alteration in the maturation of the trisomic brain and suggest future avenues for defining the effect of increased gene dosage of MMU 16 in the CNS.

Acetylcholine↗
PubMed1983

Distribution of angiotensinogen in Brattleboro rat brain.

Angiotensinogen, the precursor of angiotensin II, was quantitated in 46 brain regions of Brattleboro rats, which lack antidiuretic hormone, and Long-Evans control rats. The regional distribution of angiotensinogen in the two strains was similar except for a small number of areas which in the Brattleboro rats displayed significant decreases; namely, lateral preoptic area, medial basal hypothalamus, medial dorsal hypothalamus, lateral hypothalamus, lateral mammillary bodies, periaquaductal gray and substantia nigra. Additionally, angiotensinogen in the posterior pituitary was significantly elevated in the Brattleboro strain. These results indicate that angiotensinogen is present in the Brattleboro rat brain and that hereditary deficiency of the ability to synthesize antidiuretic hormone may be associated with a localized alteration in angiotensinogen concentration.

Angiotensinogen↗
PubMed1983

Steroid hormones as feedback regulators of brain angiotensinogen and catecholamines.

Perturbation of peripheral volume homeostasis results in regionally selective changes in brain angiotensinogen, the putative precursor of angiotensin II. The results presented indicate that brain angiotensinogen may be affected in a selective and regional manner and that steroid hormones may mediate these changes. Sex and adrenal steroids appear to affect angiotensinogen levels in different areas of the rat brain. Brain angiotensinogen and norepinephrine levels are linearly and positively correlated. Reserpinization leads to selective increases in brain angiotensinogen which are shown to be attributable to adrenal corticosterone secretion. These results point to steroids as messengers controlling in part the level of activity of brain catecholaminergic and peptidergic systems which regulate the peripheral cardiovascular system.

Angiotensinogen↗
PubMed1982

Serotonergic mechanism in the control of beta-endorphin and ACTH release in male rats.

The role of the serotonergic mechanism in the regulation of beta-endorphin (beta-EP and adrenocorticotropin (ACTH)-like immunoreactivity in plasma was investigated. Increases in beta-EP and ACTH-LI produced by quipazine maleate (QPZ), a serotonergic agonist, 1 hr after injection could be completely prevented by the serotonin (5-HT) antagonist, cinanserin (CIN), which when injected alone, decreased basal plasma concentrations of both beta-EP-LI and ACTH-LI. Concurrent injections of L-5-HTP with the 5-HT reuptake inhibitor, fluoxetine, produced an additive increase in plasma beta-EP-LI 1 hr after injection. Injection of the 5-HT antagonist, cyproheptadine, significantly decreased plasma beta-EP-LI. Stress by immobilization for 30 min or exposing the rats to 40 degree +/- 1 degree C for 30 min produced an approximate 4-fold increase in plasma beta-EP-LI and ACTH-LI, which was potentiated by I.P. injections of fluoxetine. Furthermore, the stress induced increases in plasma concentrations of beta-EP-LI and ACTH-LI were significantly reduced by the serotonin antagonists metergoline and cinanserin. These results suggest that 5-HT is a potent stimulator of both beta-EP and ACTH release and the increase in plasma concentrations of ACTH and beta-EP induced by stress are probably mediated, at least in part, by central serotonergic mechanisms.

Adrenocorticotropic Hormone↗
PubMed1980

Lactate: a major product of glutamine metabolism by human diploid fibroblasts.

Human diploid fibroblasts metabolize up to 13% of the glutamine in tissue culture medium to lactate. Four microCi of glutamine-U-14C were added to media containing 5 mM or 65 microM glucose or medium containing no added glucose, but supplemented with purine and pyrimidine nucleosides (HGTU). Aliquots of the media were taken at daily intervals and were assayed for glucose, lactate, pyruvate, malate, citrate, aspartate, glutamine, and glutamate. The label incorporation into these compounds was determined, except for glutamine and glucose. The distribution of label from glutamine-U14C in 5 mM glucose medium by day 4 was lactate (10.2%), glutamate (15.2%), citrate (1.9%), pyruvate (2.0%), malate (1.1%), and aspartate (< 0.1%). The accumulation of label in lactate and glutamate occurred continuously during the growth cycle. Malate, citrate, and aspartate accumulation occurred primarily in confluent cultures. The label in aspartate was seen only in stationary phase cells or when the glucose concentration was decreased to 65 microM or less; net aspartate accumulation was increased twofold in low glucose media. These data demonstrate an actively functioning pathway for the conversion of 4-carbon TCA-cycle intermediates to 3-carbon glycolytic intermediates in human diploid fibroblasts.

Carboxylic Acids↗
PubMed1980

The effects of ethanol on developing catecholamine neurons.

Significantly lower concentrations of norepinephrine were observed in whole brain and hypothalamus of pups exposed to ethanol pre- and post-natally as compared to controls. Dopamine levels were found to be unaltered in whole brain compared to controls although hypothalamus and corpus striatum demonstrated a decreased concentration in the experimental animals exposed to ethanol. The reduced levels of these neurotransmitters observed in the hypothalamus could reflect a direct damage to norepinephrine neurons by pre- or post-natal exposure to ethanol. However, depressed dopamine levels in the corpus striatum indicate additional injury to dopamine neurons. Alternatively, a modulatory interaction between norepinephrinergic and dopaminergic systems may be operative in these offspring. The changes observed in catecholamines could not be explained by a single and simple mode of ethanol action in the developing rat.

Aging↗
PubMed1979

A characteristic effect of hallucinogens on investigatory responding in rats.

The disruption of the temporal distribution of investigatory responses by rats in a novel hole-board following lysergic acid diethylamide-25 (LSD), as described in a companion paper (Geyer and Light, 1979), was found to be a characteristic effect of a variety of hallucinogens. Similar effects were produced by indoleamine hallucinogens, such as LSD, N,N-dimethyltryptamine, and psilocin, and by phenylethylamine hallucinogens, such as mescaline or 2,5-dimethoxy-4-methylamphetamine (DOM). Congeners of DOM that are inactive in humans had no significant effects. Furthermore, of a variety of other psychoactive drugs tested, only apomorphine produced an effect similar to that of the hallucinogens. These results suggest that a simple behavioral measure of exploration in a hole-board may provide a useful animal model with which to examine the common effects of hallucinogens.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1978

Effect of L-alanine infusion on gluconeogenesis and ketogenesis in the rat in vivo.

1. In 48 h-starved 6-week-old rats the 14C incorporation in vivo into blood glucose from a constant-specific-radioactivity pool of circulating [14c]actateconfirmed that lactate is the preferred gluconeogenic substrate. 2. Increasing the blood [alanine] to that occurrring in the fed state increased 14C incorporation into blood glucose 2.3-fold from [14c]alanine and 1.7-fold from [14c]lactate. 3. When the blood [alanine] was increased to that in the fed state, the 14C incorporation into liver glycogen from circulating [14c]alanine or [14c]lactate increased 13.5- and 1.7-fold respectively. 4. The incorporation of 14C into blood acetoacetate and 3-hydroxybutyrate from a constant-specific-radioactivity pool of circulating [14c]oleate was virtually abolished by increasing the blood [alanine] to that existing in the fed state. However, the [acetoacetate] remained unchanged, whereas [3-hydroxybutyrate] decreased, although less rapidly than did its radiochemical concentration. 5. It is concluded that during starvation in 6-week-old rats, the blood [alanine] appears to influence ketogenesis for circulating unesterfied fatty acids and inversely affects gluconeogenesis from either lactate or alanine. A different pattern of gluconeogenesis may exist for alanine and lactate as evidenced by comparative 14C incorporation into liver glycogen and blood glucose.

Acetoacetates↗
PubMed1978

The effects of lysergic acid diethylamide and mescaline-derived hallucinogens on sensory-integrative function: tactile startle.

Tactile startle responding by male Sprague-Dawley rats given 60 presentations of air-puff stimuli (37.5 psi) was measured after the intraperitoneal administration of graded doses of hallucinogens and other psychoactive drugs. Among the drugs tested were the indoleamine-derived compounds, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine and psilocin, and the phenylethylamine-derived compounds, mescaline, 2,5-dimethoxy-4-methylamphetamine and a series of active and inactive congeners of 2,5-dimethoxy-4-methylamphetamine. All of the active phenylethylamines increased startle response magnitudes throughout the test session. This pattern of augmented startle suggests that these drugs increase reactivity. However, none of the indoleamine hallucinogens increased startle responding. Of the nonhallucinogenic drugs tested, only apomorphine increased startle responding, while clonidine significantly decreased it, and amphetamine, chlorimipramine, scopolamine and methysergide had no effect. In additional studies with LSD, it was found that LSD increased the response to only the first stimulus when more intense air-puffs were used (50 psi). Furthermore, when the number of stimuli was increased from 60 to 240 (1 hr) so that appreciable habituation was evident in controls, LSD impaired this habituation. Whereas the response magnitudes of the control group decreased by 70% across the session, the responses of LSD-treated rats decreased by only 32%. These results suggest that LSD and phenylethylamine-derived hallucinogens may differ in their effects on tactile startle responding.

Animals↗
PubMed1977

Hypoketonaemic effect of L-alamine. Specific decrease in blood concentrations of 3-hydroxybutyrate in the rat.

1. The injection of L-alanine (50-100 mg/kg) into 35-day-old rats that had been starveed for 48 h increased blood L-alanine concentration to values observed in fed animals and lowered the blood concentration of 3-hydroxybutyrate within 2 min. 2. This hypoketon aemic action of L-alanine was specific for 3-hydroxybutyrate, since the acetoacetate concentrations did not change significantly. 3. The decrease in 3-hydroxybutyrate elicited by L-alanine was not related to changes in the blood concentrations of insulin, glucagon, growth hormone, glucose, unesterified fatty acids, lactate or pyruvate. 4. The injection of L-alanine resulted in a decrease in total ketones that was apparently unrelated to their increased peripheral utilization. These results are interpreted as an anti-ketogenic action of L-alanine. 5. The data suggest that L-alamine lowers ketone-body formation in starved rats, possibly via an alteration in hepatic redox equilibrium.

Acetates↗