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Biomedical subjects

R D Stith

Publications and source records attributed to R D Stith.

34 records · Page 2Linked to original sources
PubMed1982

Further characterization of putative alpha--adrenergic receptors in brain that affect blood pressure and the secretion of ACTH, GH and renin in dogs.

To determine if alpha 1-or alpha 2-adrenergic receptors mediate the inhibition of ACTH stimulation of growth hormone secretion, decrease in blood pressure and inhibition of renin secretion produced by release of catecholamines in the brain, drugs with varying amounts of alpha 1- and alpha 2-adrenergic activity were injected directly into the third ventricle in pentobarbital anesthetized dogs. To determine whether the receptors mediating the responses to clonidine were pre- or postsynaptic, the effect of intravenous clonidine was determined 2 weeks after intraventricular 6-hydroxydopamine, and 24 h after intravenous alpha-metyl-p-tyrosine. Norepinephrine, epinephrine and clonidine, but not methoxamine and phenylephrine inhibited ACTH secretion. None of these alpha-agonists affected growth hormone secretion. Epinephrine and clonidine lowered blood pressure. Clonidine decreased plasma renin activity, but the other agonists increased it. In dogs treated with 6-hydroxydopamine, the decrease in blood pressure and ACTH and renin secretion produced by clonidine was not altered but the growth hormone response was reduced. alpha-methyl-p-tyrosine had no effect on the ACTH and growth hormone responses to clonidine. The data suggest that postsynaptic alpha-adrenergic receptors mediate inhibition of ACTH secretion and stimulation of growth hormone secretion, although in the case of growth hormone secretion, a presynaptic receptor is also involved. In addition, postsynaptic alpha 2-adrenergic receptors mediate a decrease in blood pressure, and they may mediate decreased renin secretion.

Adrenergic alpha-Agonists↗
PubMed1982

Endotoxin-induced inhibition of steroid binding by mouse liver cytosol.

Glucocorticoids have been reported to ameliorate the lethal effects of endotoxin in a wide variety of animals, including man. Restoration of hepatic gluconeogenic enzymes and nucleotides may be involved in this effect. In this study decreased binding of 3H-dexamethasone was observed in liver cytosol preparations obtained from adrenalectomized C3HeB/FeJ mice treated with 100 micrograms of Escherichia coli 0111:B4 endotoxin (Boivin). Adrenalectomy significantly reduced th endotoxin LD50 value from 4.7 mg/kg to 2.3 micrograms/kg. The amount of labeled steroid bound by endotoxin-treated mice was 13,606 +/- 2,027 dpm/mg cytosol protein compared with 17,247 +/- 2,084 dpm/mg cytosol protein in adrenalectomized controls. Results from studies on the distribution of 14C-endotoxin suggested the inhibition of steroid binding seen in liver may be a mediated event. It is likely perturbations in steroid action at the subcellular/molecular level are involved.

Adrenalectomy↗
PubMed1979

Effect of a single injection of reserpine on kinetics of 3H-dexamethasone binding to receptors of the cat hypothalamus and hippocampus.

Cats were injected intraperitoneally with reserpine (5 mg/kg) or saline and sacrificed 16 h later. Hypothalamic and hippocampal cytosols were assayed for the kinetics of 3H-dexamethasone (3H-DM) binding. A parallel series was performed in which saline-injected cats were infused via venocatheter with hydrocortisone (HC). Reserpine-injected cats were infused with saline. The hypothalamic cytosol of reserpinized cats showed a marked decrease in 3H-DM binding capacity relative to that from saline-treated cats. Hippocampal cytosol 3H-DM binding capacity was unaffected by reserpinization. Infusion of high levels of HC reduced the amount of 3H-DM binding in the hypothalamus, but did not account for all the reduction found after reserpine treatment. HC infusion had no effect on hippocampal binding capacity. Reserpine treatment did not change the dissociation constant differences between the two brain regions. The data suggest that depletion of neurotransmitters by reserpine treatment from the hypothalamus, but not the hippocampus, significantly reduces the number of 3H-DM binding sites and that such a reduction is due, in part, to the effects of reserpine and not to high circulating levels of HC.

Animals↗
PubMed1978

In vitro nuclear 3H-hydrocortisone binding in the hypothalamus of the pig.

Hypothalamic cell nuclear uptake and binding of 3H-hydrocortisone (3H-HC)-receptor complexes were studied in a cell-free system. Greater net concentrations of radioactivity were found in the 0.4 M KCl non-extractable fraction (sediment) in the first 20 min of incubation and in the 0.4 M KCl extractable fraction (supernatant) from 30 to 60 min. Incubation in low ionic strength medium favored localization of radioactivity in the supernatant, whereas high ionic strength promoted greated localization in the sediment. Specific binding in the supernatant was non-saturable, but reached a plateau in the sediment at about 5 X 10(-8)M 3H-HC. The observed value of Kd for binding in the nuclear sediment was 4.88 X 10(9)M-1 and the maximum number of binding sites was 8.8 femtomoles/mg DNA. RNA polymerase activity increased by 59% in the presence of hormone-receptors over that in the presence of free hormone in buffer.

Animals↗
PubMed1976

Uptake and binding of [3H]hydrocortisone by various pig brain regions.

The cytosol fraction of septum, hypothalamus, and hippocampus of intact and adrenalectomized pigs possessed greater concentrations of radioactivity than the cytosol fraction of amygdala, pituitary, and cortex after an intraventricular injection of [1,2-3H]hydrocortisone. Nuclear extracts from the same brain regions possessed higher concentrations of radioactivity than nuclear extracts of the other brain regions of intact pigs. Nuclear extracts of amygdala, pituitary and hypothalamus from adrenalectomized pigs exhibited the greatest increase over intact pigs in labeled hormone concentration. When adrenalectomized pigs were administered dexamethasone prior to [3H]hydrocortisone, uptake of label was most depressed in hippocampal cytosol and cuclear extract. Also sensitive to the competitive effects of dexamethasone were septal and pituitary nuclear extracts. In intact pigs, pituitary, hippocampus and cortex exhibited higher ratios of bound to total hormone in the cytososl fraction than the other brain regions. Hippocampal and amygdala cytosol possessed the greater magnitude of increase in the ratio of bound to total hormone in adrenalectomized versus intact pigs. The pituitary, septum, amygdala, and cortex of intact and adrenalectomized pigs possessed a ratio of bound to total hormone in nuclear extract 5-10 times greater than that in hippocampus and hypothalamus. However, the latter two regions exhibited a greater increase in bound: total hormone after administration of labeled hormone to adrenalectomized pigs than nuclear extracts of the other brain regions.

Adrenal Glands↗
PubMed1976

Effects of hippocampal and amygdalar stimulation on uptake and binding of 3H-hydrocortisone in the hypothalamus of the cat.

Stimulation of the hippocampus or amygdala of adrenalectomized cats occurred for 10 sec followed by a 50 sec period of no stimulation, beginning 30 min prior to and ending 30 min after administration of 100 muCi of 3H-hydrocortisone into a lateral ventricle. Sixty min after administration of labeled hormone, the hypothalamus was excised and homogenized. Cytosol and nuclear extract fractions were obtained and analyzed for radioactivity and protein content. Separation of bound from free hydrocortisone was achieved by charcoal and adsorption assay. Results reveal that stimulation of the hippocampus resulted in a greater concentration of 3H-hydrocortisone taken up into hypothalamic cells. Also, a greater percentage of total hormone found in the nuclear extract was assayed as bound 3H-hydrocortisone, and the concentration of bound radioactivity in the nuclear extract was increased over control values. Amygdalar stimulation, in general, yielded results similar to those obtained from control cats. However, although a lesser percentage of total hormone in the hypothalamic cytosol was assayed as bound hormone, there was a greater concentration of nuclear bound hormone than in controls, but less than that determined in the hippocampal stimulation group. These results add to the evidence that hippocampus and amygdala have a modulating influence upon the hypothalamo-hypophyseal axis. They also suggest that one manner in which these limbic structures may influence hypothalamic function is to modulate the uptake and binding of hydrocortisone in hypothalamic cells.

Adrenal Glands↗
PubMed1976

Metyrapone inhibition of 3H-hydrocortisone uptake and binding in various brain regions of the pig.

Metyrapone (MET) inhibition of hydrocortisone (3H-HC) uptake binding in the cytosol and nucleus of various brain regions of the pig was demonstrated in vivo. The hippocampus, hypothalamus and septum were the regions most sensitive to the inhibition by MET. The hippocampus exhibited the greatest reduction in 3H-HC concentration in whole homogenate, bound in cytosol and in nuclei. The anterior pituitary and cerebral cortex were the least sensitive to MET. In vitro incubation of hypothalami with 3H-HC and MET substantiated the results obtained in vivo with regard to the inhibitory action of MET on 3H-HC uptake and binding. These results were interpreted to indicate the MET may act directly in certain brain regions and that this inhibitory aciton has important implications for both experimental and clinical uses of this drug.

Adrenalectomy↗
PubMedDate not supplied

Myocardial contractile protein ATPase activities in adrenalectomized and thyroidectomized rats.

This report compares the effects of adrenalectomy and thyroidectomy, with and without hormone replacement, on loss of contractile protein ATPase activities. The rationale for this study was derived from the similarities in their intracellular receptors, mechanisms of action, and the large number of proteins regulated by both hormones. Rats were adrenalectomized, thyroidectomized, or both, and were subsequently treated for 6 weeks with hydrocortisone, triiodothyronine, or saline. Sham-operated rats were given saline for the same period of time. Six weeks of adrenal insufficiency resulted in diminished enzymatic activity of myofibrillar, Ca(2+)-activated myosin ATPase, and actin-activated myosin ATPase fractions. Treatment with hydrocortisone prevented the decline in enzymatic activity due to adrenalectomy. Likewise, thyroidectomy caused a loss of enzymatic activity which was prevented by treatment with triiodothyronine. The full deleterious effect of combined ablation could be partially prevented by treatment with either hydrocortisone or triiodothyronine, but the latter was most effective. The results suggest that hydrocortisone and triiodothyronine each had significant positive effects in the presence of the other, but not in its absence, on the activity of myofibrillar Ca(2+)-dependent Mg-ATPase and Ca(2+)-activated myosin ATPase. The effects of these two hormones on actin-activated myosin ATPase activity were more independent of each other. We conclude that the actions of thyroid and glucocorticoid hormones on the heart are interrelated and that optimum myocardial function results from their combined action.

Adenosine Triphosphatases↗
PubMedDate not supplied

Effects of riboflavin analogues and diuretics on the spontaneously hypertensive rat heart.

The chronic treatment of spontaneously hypertensive rats (SHR) with 7,8-dimethyl-10-(3-chlorobenzyl) isoalloxazine [CBI], 7,8-diethyl-10-aminol isoalloxazine [DEAI], enduron (methyclothiazide) and amiloride were studied for their effects on blood pressure and cardiac contractile protein ATPase activities. After 35 weeks of treatment all the above antihypertensive agents showed a decrease in blood pressure in the SHR (p less than 0.01). Chronic treatment with CBI, DEAI, enduron, and amiloride significantly improved the myofibrillar ATPase activity at all pCa2+ concentrations (p less than 0.01). Furthermore, CBI, DEAI, enduron, and amiloride drug treatments enhanced actin-activated myosin ATPase activity (p less than 0.01). The Ca2(+)-activated myosin ATPase activity was significantly elevated after treating with CBI and DEAI (p less than 0.01). These results suggest that the antihypertensive agents used in this study helped in reducing the blood pressure with a subsequent increase in myocardial contractile protein ATPase activity.

Actins↗