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Biomedical subjects

R L Hauger

Publications and source records attributed to R L Hauger.

At least 73 records · Page 4Linked to original sources
PubMed1989

Individual behavioral and neuroendocrine differences in responsiveness to audiogenic stress.

A relatively wide range of individual differences in neuroendocrine, immune and behavioral components of the audiogenic stress response has been found. In this study, an analysis of the association between the physiological and behavioral measures revealed that the degree of noise-induced suppression of both general activity and ingestive behaviors was significantly correlated with activation of adrenal steroid secretion following both acute and repeated noise exposures. Splenic natural killer cytotoxicity was not correlated with the behavioral measures of the stress response. Characterization of individual behavioral response profiles may be needed to evaluate accurately the neuroendocrine effects of stress.

Animals↗
PubMed1989

Central corticotropin releasing factor reduces natural cytotoxicity. Time course of action.

Corticotropin-releasing factor (CRF) administered intracerebroventricularly produced both a rapid, greater than 50% reduction in splenic natural killer (NK) cytotoxicity and a prolonged elevation in plasma corticosterone levels. In the first 60 minutes following CRF, fivefold increases in corticosterone levels were associated with the suppression of NK activity. However, NK activity returned to control levels at later time points even though elevated plasma corticosterone levels persisted. These data augment the findings that central CRF reduces natural cytotoxicity and establish a time course for the effect in acutely treated rats.

Animals↗
PubMed1988

Adaptation to chronic stress. Temporal pattern of immune and neuroendocrine correlates.

Stress-inducing stimuli are associated with a suppression of immune function. In this study, the relationship between pituitary-adrenal hormone release and natural cytoxicity was examined in the rat during single and repeated instances of chronic stress. Increased plasma concentrations of both adrenocorticotropic hormone (ACTH) and beta-endorphin/lipotropin were correlated with increases in natural killer (NK) activity following a single period of immobilization. After 4 days of repeated daily immobilization (2.5 hours/day), the secretory response of beta-endorphin/lipotropin was similar to that on day 1, but NK activity was lower than on day 1. These observations suggest a complex interaction between pituitary-adrenal responses to stress and changes in natural cytoxicity.

Adrenocorticotropic Hormone↗
PubMed1988

Dissociation of norepinephrine turnover from alpha-2 responses after clorgiline.

Responses to intravenous clonidine, a possible central noradrenergic probe, were examined in patients with depression before and after treatment with clorgiline, a selective monoamine oxidase type A inhibitor. Pulse rate, mean arterial blood pressure, plasma norepinephrine, 3-methoxy-4-hydroxyphenylglycol, and growth hormone were measured. Clorgiline treatment (2.5 to 10 mg/day) produced a variable reduction in the hypotensive response to clonidine but did not influence heart rate or plasma norepinephrine responses. Clorgiline markedly reduced the urinary output of norepinephrine and metabolites, indicating a reduced turnover of norepinephrine. None of the measured parameters corresponded with clinical effect. These data suggest that any clorgiline-induced alterations in alpha 2-receptor function as measured by responses to clonidine are modest and highly variable. Furthermore, since the variable and inconsistent changes in alpha 2-receptor function are dissociated from the massive changes in norepinephrine metabolism, regulation of presynaptic alpha 2-receptors appears unlikely to mediate the effects of clorgiline in patients with depression.

Bipolar Disorder↗
PubMed1988

CRF activates autonomic nervous system and reduces natural killer cytotoxicity.

Corticotropin-releasing factor (CRF) acts within the brain to elicit changes in neuroendocrine, autonomic, and behavioral activity similar to those observed after stress. A reduction of immune function has also been described following central administration of CRF. In this study, we examined whether autonomic nervous system activation plays a role in CRF-induced suppression of natural killer (NK) cytotoxicity. synthetic rat CRF (1.0 microgram) microinjected into the lateral ventricle significantly increased plasma concentrations of norepinephrine and reduced splenic NK cell activity in the rat. Pretreatment of the animals with the ganglionic-blocking agent chlorisondamine completely abolished the CRF-induced increase in plasma norepinephrine levels and reduction in NK activity. However, CRF-induced elevations in plasma levels of adrenocorticotropic hormone and corticosterone were not affected by chlorisondamine. The results of this study suggest that activation of the sympathetic nervous system plays a role in CRF-induced suppression of NK cytotoxicity.

Adrenocorticotropic Hormone↗
PubMed1988

Corticotropin-releasing factor receptors and pituitary adrenal responses during immobilization stress.

The regulation of pituitary and brain CRF receptors and corticotroph responses during stress were studied in rats subjected to prolonged immobilization. Plasma ACTH levels showed the characteristic biphasic changes, with a rapid 23-fold increase in 15 min, followed by a decrease to about twice the basal levels after 6-h immobilization. In contrast, plasma corticosterone levels were markedly elevated throughout the duration of the stress. Pituitary CRF receptor content, measured by binding of [125I]Tyr-ovine CRF to pituitary membrane-rich fractions, was unchanged after 2.5 h, but was reduced by 28 +/- 2.7% (+/- SE) and 47.6 +/- 1.1% after 18 and 48 h of immobilization, respectively. These results were confirmed by autoradiography in slide-mounted frozen pituitary sections. In contrast, no changes in CRF receptor content were observed in brain areas, including olfactory bulb, frontoparietal cortex, hippocampus, amygdala, and lateral septum. A concomitant decrease in immunoreactive (ir) CRF content in the median eminence of rats immobilized for 48 h is consistent with the hypothesis that increased release of CRF into the portal circulation occurs during chronic stress. Despite pituitary CRF receptor loss and reduced in vitro responses to CRF, the increases in plasma ACTH and corticosterone in vivo after ether exposure or CRF injection were greater and more prolonged in rats immobilized for 48 h than in nonimmobilized controls. The decrease in pituitary CRF receptors was accompanied by decreased CRF-stimulated cAMP and ACTH release in cultured pituitary cells from 48-h restrained rats. However, concomitant incubation of cells with CRF and vasopressin restored cAMP and ACTH responses to control levels, suggesting that the simultaneous release of both regulators from the hypothalamus determines the plasma ACTH level. These findings indicate that the decrease in plasma ACTH during the adaptation phase to stress is accompanied by decreases in pituitary CRF receptors. However, the enhanced pituitary response to a superimposed stress or CRF injection implies that the decrease in plasma ACTH levels during prolonged stress may be due to adaptive changes at the central level. These findings emphasize the importance of the integrated actions of CRF and other regulators in the control of the pituitary adrenal-axis during stress.

Adrenal Glands↗
PubMed1987

Differential regulation of brain and pituitary corticotropin-releasing factor receptors by corticosterone.

The regulatory actions of CRF during the neuroendocrine response to stress are mediated by specific receptors within the nervous system and the anterior pituitary gland. Glucocorticoids exert negative feedback inhibition on ACTH secretion by interacting at the pituitary corticotrophs and the central nervous system. To determine whether glucocorticoids influence ACTH secretion by regulating the concentration of CRF receptor sites, binding of [125I]Tyr-oCRF to pituitary and brain membrane-rich particles was studied after glucocorticoid treatment. Corticosterone administration (0.5-150 mg/day) for 1-4 days in adult male rats caused a dose-dependent decrease in the number of CRF receptors in the anterior pituitary in parallel with the reduction in ACTH secretion. In the brain, binding studies in membrane-rich fractions or by autoradiography in slide-mounted frozen sections revealed no changes in CRF receptors in the cortex, hippocampus, amygdala, septal area, and olfactory bulb, although circulating corticosterone levels were higher than during stress. The selective down-regulation of anterior pituitary CRF receptors after corticosterone administration, without alterations in brain CRF receptors, is similar to the change in CRF receptors previously reported after adrenalectomy and indicates that receptor regulatory mechanisms in secretory cells differ from those in neural tissue. Furthermore, the decrease in pituitary CRF receptors after physiological increases in circulating glucocorticoids may contribute to the inhibitory effects of adrenal steroids on ACTH secretion.

Adrenocorticotropic Hormone↗
PubMed1986

Glucostatic regulation of hypothalamic and brainstem [3H](+)-amphetamine binding during food deprivation and refeeding.

Saturable and stereospecific binding sites for [3H](+)-amphetamine have been identified in rat hypothalamus and structure-activity studies suggest that these sites may mediate the anorectic actions of amphetamine and related phenylethylamines. In order to determine whether these binding sites may be involved in the physiological control of appetite, [3H](+)-amphetamine binding was measured in crude synaptosomal membranes prepared from various brain regions following food deprivation and refeeding. Rats deprived of food for 24 to 72 h exhibited time-dependent reductions in body weight, blood glucose concentration, and specific [3H](+)-amphetamine binding in hypothalamus and brainstem. No change in specific [3H](+)-amphetamine binding was found in the frontal cortex, striatum, cerebellum, or liver prepared from these same animals. The decrease in specific [3H](+)-amphetamine binding in both the hypothalamus and brain stem following food deprivation was rapidly and completely reversed by allowing animals brief access to food or a 10% glucose solution. The changes in [3H](+)-amphetamine binding in hypothalami and brainstem of food-deprived and refed rats were also highly correlated with blood glucose concentration. Further, parenteral administration of D-glucose, but not L-glucose, to either fed or food-deprived rats significantly increased the number of [3H](+)-amphetamine binding sites in hypothalamus. These data suggest that the [3H](+)-amphetamine binding site in the hypothalamus and (or) brainstem may function in the 'glucostatic' regulation of appetite.

Animals↗
PubMed1986

Distribution of corticotropin-releasing factor receptors in primate brain.

The distribution and properties of receptors for corticotropin-releasing factor (CRF) were analyzed in the brain of cynomolgus monkeys. Binding of [125I]tyrosine-labeled ovine CRF to frontal cortex and amygdala membrane-rich fractions was saturable, specific, and time- and temperature-dependent, reaching equilibrium in 30 min at 23 degrees C. Scatchard analysis of the binding data indicated one class of high-affinity sites with a Kd of 1 nM and a concentration of 125 fmol/mg (approximately equal to 30% of the receptor number in monkey anterior pituitary membranes). As in the rat pituitary and brain, CRF receptors in monkey cerebral cortex and amygdala were coupled to adenylate cyclase. Autoradiographic analysis of specific CRF binding in brain sections revealed that the receptors were widely distributed in the cerebral cortex and limbic system. Receptor density was highest in the pars tuberalis of the pituitary and throughout the cerebral cortex, specifically in the prefrontal, frontal, orbital, cingulate, insular, and temporal areas, and in the cerebellar cortex. A very high binding density was also present in the hippocampus, mainly in the dentate gyrus, and in the arcuate nucleus and nucleus tuberis lateralis. A high binding density was present in the amygdaloid complex and mamillary bodies, olfactory tubercle, and medial portion of the dorsomedial nucleus of the thalamus. A moderate binding density was found in the nucleus accumbens, claustrum, caudate-putamen, paraventricular and posterior lateral nuclei of the thalamus, inferior colliculus, and dorsal parabrachial nucleus. A low binding density was present in the superior colliculus, locus coeruleus, substantia gelatinosa, preoptic area, septal area, and bed nucleus of the stria terminalis. These data demonstrate that receptors for CRF are present within the primate brain at areas related to the central control of visceral function and behavior, suggesting that brain CRF may serve as a neurotransmitter in the coordination of endocrine and neural mechanisms involved in the response to stress.

Adenylyl Cyclases↗
PubMed1986

Receptor-mediated actions of corticotropin-releasing factor in pituitary gland and nervous system.

High-affinity corticotropin-releasing factor (CRF) receptors which mediate the actions of the hypothalamic peptide on adrenocorticotropic hormone (ACTH) release have been identified in the rat anterior pituitary gland. Occupancy of the pituitary receptor by CRF agonists stimulates ACTH release via activation of adenylate cyclase and cyclic adenosine monophosphate dependent protein kinase. In the regulation of ACTH secretion, the effects of CRF on the corticotroph are integrated with the stimulatory actions of cyclic adenosine monophosphate-independent stimuli such as angiotensin II, vasopressin and norepinephrine, and the inhibitory effects of glucocorticoids and somatostatin. In contrast to the major importance of the inhibitory effect of glucocorticoid feedback on ACTH secretion, somatostatin has relatively little effect on CRF-stimulated ACTH release in the normal rat corticotroph. Following adrenalectomy, the progressive elevation of plasma ACTH levels is accompanied by a concomitant decrease in pituitary CRF receptors. The postadrenalectomy loss of CRF receptors, which is prevented by dexamethasone treatment, is caused by a combination of occupancy and processing of the pituitary sites during increased secretion of the hypothalamic peptide. Recently, specific receptors for CRF have been localized in the rat and monkey brain and adrenal medulla, where they are also coupled to adenylate cyclase. Brain CRF receptors are most abundant in the cerebral and cerebellar cortices and in structures related to the limbic system and control of the autonomic nervous system. The actions of CRF on the central and peripheral nervous systems, as well as on the pituitary gland, emphasize the role of CRF as a key hormone in the integrated response to stress.

Adrenocorticotropic Hormone↗
PubMed1985

The effect of clorgyline on noradrenergic function.

A low dosage of the specific MAO-A inhibitor clorgyline (5-10 mg/day) was administered chronically to 10 depressed patients. Peripheral noradrenergic activity, as assessed by measurements of the plasma norepinephrine (NE) concentration, heart rate, and blood pressure, was determined before and after drug treatment. The administration of a low dosage of clorgyline was associated with a decrement in peripheral presynaptic noradrenergic activity. Comparison with the results of similar studies of the effects of desmethylimipramine (DMI) suggests that antidepressant drugs with unrelated primary actions affect peripheral noradrenergic functions differently.

Adult↗
PubMed1985

Glucostatic regulation of (+)-[3H]amphetamine binding in the hypothalamus: correlation with Na+,K+-ATPase activity.

Preincubation of rat hypothalamic slices in glucose-free Krebs-Ringer buffer (37 degrees C) resulted in a time-dependent decrease in specific (+)-[3H]amphetamine binding in the crude synaptosomal fraction prepared from these slices. The addition of D-glucose resulted in a dose- and time-dependent stimulation of (+)-[3H]amphetamine binding, whereas incubation with L-glucose, 2-deoxy-D-glucose, or 3-O-methyl-D-glucose failed to increase the number of (+)-[3H]amphetamine binding sites. Ouabain potently inhibited the glucose-induced stimulation of (+)-[3H]amphetamine binding, suggesting the involvement of Na+,K+-ATPase. Preincubation of hypothalamic slices with glucose also resulted in an increase in Na+,K+-ATPase activity and the number of specific "high-affinity" binding sites for [3H]ouabain, and a good correlation was observed (r = 0.89; P less than 0.02) between the glucose-stimulated increase in (+)-[3H]amphetamine and [3H]ouabain binding. Similar increases in (+)-[3H]amphetamine binding, [3H]ouabain binding, and Na+,K+-ATPase activity were observed in the hypothalamus after parenteral administration of glucose to rats. The administration of anorectic doses of amphetamine (0.1-5.0 mg/kg of body weight) also increased Na+,K+-ATPase activity in the hypothalamus. These data suggest that the (+)-[3H]amphetamine binding site in hypothalamus, previously linked to the anorectic actions of various phenylethylamines, is regulated both in vitro and in vivo by physiological concentrations of glucose. Glucose and amphetamine appear to interact at common sites in the hypothalamus to stimulate Na+,K+-ATPase activity, and the latter may be involved in the "glucostatic" regulation of appetite.

Animals↗
PubMed1984

Characteristics of [3H](+)-amphetamine binding sites in the rat central nervous system.

Recent studies in our laboratory have demonstrated the presence of specific binding sites for [3H] (+)-amphetamine in crude membrane preparations derived from rat brain. In this report we have further characterized the specific binding of [3H] (+)-amphetamine in various subcellular fractions of rat brain and demonstrate a greater than five-fold enrichment in the crude synaptosomal (P2) fraction compared to a crude membrane preparation. Specific [3H] (+)-amphetamine binding in crude synaptosomal membranes is saturable and stereospecific with an apparent dissociation constant, Kd, of 2.8 +/- 0.5 microM and an estimated maximum number of binding sites, Bmax, of 60.4 +/- 8.4 pmoles/mg protein derived by Scatchard or Klotz analysis of binding data using filtration assays. Centrifugation assays yield a similar Kd though the apparent Bmax is higher. In addition specific [3H] (+)-amphetamine binding is: rapidly reversible, temperature sensitive, labile to preincubation in Tris buffer, inhibited by sodium ions and unevenly distributed in various brain regions. Specific [3H] (+)-amphetamine binding sites are found almost exclusively in the rat central nervous system (the brainstem, hypothalamus, and striatum exhibiting relatively high levels of binding), whereas peripheral tissues such as liver, kidney and heart have very low to undetectable levels of specific binding.

Amphetamine↗
PubMed1982

Characterization of angiotensin II receptors in the anterior pituitary gland.

Specific and high affinity binding sites for angiotensin II were demonstrated in the anterior pituitary gland by binding studies with [125I] iodoangiotensin II. The binding properties of the pituitary receptors were similar to those of angiotensin II receptors present in the adrenal gland. The concentration of binding sites in rat anterior pituitary (293 +/- 50 fmoles/mg protein) was less than in the adrenal gland, but was much greater than in smooth muscle. Angiotensin II receptors were identified in the anterior pituitary tissue of mature and immature animals of both sexes, and in species including rat, rabbit and dog. No binding of angiotensin II was detected in posterior pituitary homogenates, or in GH3 pituitary tumor cells. Collagenase-dispersed anterior pituitary cells also contained specific binding sites for angiotensin II, with equilibrium binding constant (Ka) of 3.6 x 10(9) M-1. The presence of specific high-affinity angiotensin II receptor in the anterior pituitary gland provides a mechanism by which angiotensin-like peptides could modulate the process of pituitary hormone secretion.

Angiotensin II↗