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Biomedical subjects

E M Dax

Publications and source records attributed to E M Dax.

At least 55 records · Page 3Linked to original sources
PubMed1988

Age-associated changes in pineal adrenergic receptors and melatonin synthesizing enzymes in the Wistar rat.

The nocturnal stimulation of pineal melatonin synthesis and elevation of serum melatonin is known to be reduced in old age in several species. In Wistar rats the capacity of the beta-adrenoceptor to develop supersensitivity (increase in Bmax) during the light period of the diurnal light/dark cycle is lost during maturation (3-6 months) rather than old age. Further, the present study shows that neither the alpha 1- nor beta-adrenoceptor density of the pineal declines as rats age. Pineal hydroxyindole-O-methyltransferase activity does fall (17-55%) in rats after 18 months of age, but nocturnal pineal arylalkylamine N-acetyltransferase activity is not significantly altered. Thus, from examination of these parameters across the life span of the rat, it seems likely that the reported reduction in serum melatonin in old animals is related to a reduced capacity of the pineal to synthesize melatonin, rather than an altered responsiveness of the gland to neural stimulation.

Acetylserotonin O-Methyltransferase↗
PubMed1988

Beta endorphin and dynorphin levels in rat pituitary and hypothalamus: age studies.

The content of immunoreactive (ir)-beta-endorphin, ir-dynorphin 1-17, and ir-dynorphin 1-8 was determined in hypothalamus, anterior pituitary, and neurointermediate lobe of rats 3-24 months of age. In the anterior pituitary ir-beta-endorphin showed a progressive rise with age (0.5 +/- 0.06 ng/tissue at 3 months to 1.02 +/- 0.23 at 24 months); a similar change was seen in ir-adrenocorticotropic hormone content of the same tissues. No age-related change in neurointermediate lobe ir-endorphin content was observed. In the hypothalamus, the ir-beta-endorphin content fell progressively from 3 to 18 months, but was restored at 24 months to levels indistinguishable from those at 3 months (16.2 +/- 4.3 ng/tissue compared with 11.3 +/- 4.0 at 24 months). The ir-dynorphin content did not change progressively over the age span examined, except in the case of anterior pituitary content of ir-dynorphin 1-17 which fell progressively between 3 and 18 months (from 1.65 +/- 0.15 ng/tissue at 3 months to 0.73 +/- 0.12). Radioimmunoassay following high-performance liquid chromatography analysis of extracts of the tissues showed little variation of the immunoreactive forms with age, with two notable exceptions. In the hypothalamic extracts from 24-month-old rats the ratio of the nonacetylated ir-endorphin to the acetylated ir-endorphin was lower than in equivalent extracts from 3-month-old rats. In anterior pituitary extracts from 3-month-old rats, ir-dynorphin 1-17 appeared as two peaks (putative 6K and 4K species) of approximately equal size.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1988

Nitrite inhalants: patterns of abuse in Baltimore and Washington, D.C.

Nitrite inhalants, as drugs of abuse, have received a new prominence in the literature since their use has been associated with Kaposi's Sarcoma and possibly other manifestations of acquired immunodeficiency syndrome (AIDS). Changes in patterns and prevalence of use have not been investigated since the onset of the AIDS epidemic. We have examined the abuse patterns of nitrite inhalants (poppers) in several different groups. The use of poppers among drug abusers in the Baltimore-Washington, D.C. metropolitan area has remained constant over the past 5 years, with the prevalence of use being approximately 11% for recreational drug users and 22% for heavy abusers. Self-reported use by a homosexual group had decreased over the same time period. Sixty-nine percent of the homosexual sample had experience with nitrities, but only 21% had used them in the 6 months prior to being surveyed. The mean interval since last use was 25 months, and since peak use, 4.1 years. Among substance abusers, nitrites appear to be a drug whose use starts late, with the mean age of first use being 25.6 years compared to 14.6 years for glue, 17.6 years for marijuana, and 18.5 years for heroin. We found both heterosexual and homosexual groups utilize nitrites primarily to "get high," but homosexuals more often use them during overt sexual activity. Experience with amyl nitrite was much more prevalent than that with the butyl derivative in both populations. We conclude that the prevalence of nitrite abuse among drug users has not changed as a result of the AIDS epidemic, but such use appears to have decreased within the homosexual community.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Beta-adrenergic receptors, glucagon receptors, and their relationship to adenylate cyclase in rat liver during aging.

The beta-adrenergic and glucagon receptor-binding capacities in rat livers from 6-27 months of age were measured to investigate the mechanism of a previously observed rise in beta-adrenergic stimulated adenylate cyclase with increasing age. There was no concomitant increase in glucagon-stimulated adenylate cyclase. In the present study neither glucagon-binding capacity nor glucagon-stimulated adenylate cyclase changed with age. In contrast, the beta-adrenergic receptor capacity, measured in the same membranes by [125I]iodopindolol binding, increased nearly 3-fold from 6.6 +/- 0.6 fmol/mg at 6 months to 19.1 +/- 3.3 fmol/mg at 18-19 months. The increase was directly proportional to the maximum isoproterenol-stimulated adenylate cyclase activity in livers of rats up to 19 months of age. By 24-27 months the binding capacity had increased to 24.9 +/- 3.3 fmol/mg, but there was no further increase in adenylate cyclase activity. Thus, there appeared to be a beta-receptor-adenylate cyclase uncoupling in livers from the senescent animals (25-27 months). The defect could not be demonstrated by studies examining isoproterenol competition of [125I]iodopindolol from agonist-induced high affinity sites on the membranes, a procedure that examines receptor-Ns protein coupling. Activation of adenylate cyclase by the nonhormonal stimulators F- and forskolin did not change with age, indicating that the catalytic unit was not a limiting factor. Since the relationship between the glucagon receptor and adenylate cyclase also remained unaltered, the uncoupling apparently lies in an alteration of the interaction between the beta-adrenergic receptor and the guanine nucleotide-sensitive Ns protein.

Adenylyl Cyclases↗
PubMed1987

Age-related changes in membrane receptor interactions.

The relevance of membrane receptor systems to aging in animals has been studied extensively. A large number of hormones, drugs, and transmitters convey their signals via membrane receptors. Many physiologic and biochemical processes are mediated via membrane receptors. Therefore, exploration of the age-related changes in the interactions of receptors with coupling proteins second-messenger systems and their surrounding environments are of obvious significance.

Aging↗
PubMed1987

HIV infection and international travel.

Screening international travelers for human immunodeficiency virus (HIV) antibodies does little to prevent the spread of the acquired immune deficiency syndrome. Individuals who are seropositive for HIV antibodies and wish to travel abroad will be subject to varying restrictions, depending on the severity of their illness and the entrance requirements for specific countries. International travel is not a risk factor for HIV infection, since routes of HIV transmission appear to be uniform worldwide. However, prudent precautions are recommended because international travel may modify an individual's risk profile.

Acquired Immunodeficiency Syndrome↗
PubMed1986

(-)[125I]iodopindolol binding to beta-adrenergic receptors in tissues of the rat with particular reference to the characterization in liver.

The high affinity beta-adrenergic antagonist (-)[125I]iodopindolol was used to characterize and quantitate beta-adrenergic binding in liver and other tissues of the rat. Saturable, stereospecific binding with typical characteristics of beta-adrenergic receptors was demonstrated in all tissues examined (liver, lung, heart, kidney, fat and brain). Unlike the case with other radioactive ligands that have been used to measure beta-adrenergic receptors, assays were possible in crude homogenates as well as in purified membranes. Specific binding was defined as [125I]iodopindolol displaced by 0.1 mM isoproterenol. The percentage of [125I]iodopindolol specifically bound was greater than with other labelled antagonist ligands and it ranged from 95-60% of total binding over [125I]iodopindolol concentrations of 15-1000 pM. beta-Adrenergic binding could be quantitated in liver of animals of all ages whereas previously quantitation in liver was possible only using rats less than 2 months of age. Binding capacities ranged from a low of approximately 6 fmol/mg in liver particles precipitated at 4500 g to approximately 550 fmol/mg in 4500 g lung particles. The Kd of binding obtained by kinetic analysis was similar in all tissues. [125I]Iodopindolol is a nearly ideal ligand for the quantitation of beta-adrenergic receptors in various tissues of the rat. Because of its high affinity, stability and availability at high specific activity, this ligand should be especially useful in physiological studies requiring the accurate quantitation of receptor capacities.

Adrenergic beta-Agonists↗
PubMed1985

Ectopic beta-adrenergic receptors coupled to adenylate cyclase in human adrenocortical carcinomas.

The adenylate cyclase of an adrenocortical carcinoma of the rat is activated not only by ACTH but also by beta-adrenergic agonists, which bind to ectopic beta-adrenergic receptors not present in normal rat adrenal cortex. Previous reports examining possible beta-adrenergic control of adenylate cyclase in human adrenocortical carcinomas failed to demonstrate beta-adrenergic receptor-linked enzyme activity. We studied six human adrenal carcinomas and normal adrenal cortex from three subjects for beta-adrenergic agonist-sensitive adenylate cyclase and beta-adrenergic binding sites. Three of the six carcinomas had adenylate cyclase responses to both ACTH and beta-agonists. Two tumors were ACTH responsive but not beta-agonist responsive; one tumor responded to beta-agonists but not to ACTH. Adenylate cyclase activity of normal adrenal cortex from three subjects was stimulated by ACTH but not by beta-agonists. In membrane preparations from three tumors with beta-agonist-sensitive adenylate cyclase, the radiolabeled beta-adrenergic antagonist [125I]pindolol bound specifically and with high affinity (Kd = 38-83 pM) to a single class of binding sites which showed saturation with ligand concentration, reversibility of binding, pharmacological specificity, and stereospecificity. Normal cortex and one tumor without beta-adrenergic agonist-sensitive adenylate cyclase had no specific binding of [125I]pindolol. These results indicate that malignant transformation of adrenal cortex in man is frequently but not invariably associated with the appearance of ectopic beta-adrenergic receptors functionally linked to adenylate cyclase. Loss of ACTH-responsive adenylate cyclase may also occur simultaneously with the development of beta-adrenergic receptor-linked adenylate cyclase.

Adenylyl Cyclases↗
PubMed1984

Adipocyte hormone responsiveness and aging in the rat: problems in the interpretation of aging research.

Fat is a metabolically dynamic tissue. Its metabolism is under the control of several well-characterized hormonal systems. There appear to be changes in the hormonal sensitivity of rat fat with age. No single mechanism has been proved to explain all the changes observed in adipocyte hormonal responsiveness with aging, although it does seem likely that age does have an independent effect on fat metabolism from studies to date.

Adenylyl Cyclases↗
PubMed1982

Loss of rat ventricular alpha 1-adrenergic receptors during aging.

Ventricular alpha 1-adrenergic receptor concentration, measured by specific binding of [3H]-prazosin, decreases by 33% as rats age from 3 to 24 months. No age changes occur in binding affinity for [3H]-prazosin or potency of various alpha-adrenergic agonists and antagonists to displace [3H]-prazosin. The ratio of membrane protein to ventricular wet weight also does not change significantly with age. These results suggest a possible mechanism for loss of cardiovascular alpha-adrenergic responsiveness during aging.

Aging↗
PubMed1982

Regeneration of beta-adrenergic receptors in senescent rats: a study using an irreversible binding antagonist.

The drug used in this study, bromoacetylalprenololmenthane, has the ability to bind and block irreversibly beta-adrenergic receptors. The drug was bound to membranes prepared from hearts, lungs, and brains of both senescent and young rats with a similar affinity. When this drug was injected into rats in nontoxic doses (up to 70 mg/kg), up to 90% of beta-adrenergic receptors were irreversibly blocked 4 hr after injection, whereas the injection of similar amounts of (+/-)-alprenolol was without effect on receptor number. In senescent animals this blockade lasted considerably longer than in young animals; receptor numbers in hearts and lungs of senescent rats returned to control levels only 1 month after injection. The number of beta-adrenergic receptors in brains of senescent rats was unaffected by this drug. Thus, based upon the long-lasting blockade of beta-adrenergic receptors in therapeutically important organs, it appears that irreversible binding blockers may have potential in the treatments of senescent organisms.

Adrenergic beta-Antagonists↗
PubMed1982

Adrenergic ligand liposolubility in membranes. Direct assessment in a beta-adrenergic binding system.

The binding of [3H]dihydroalprenolol to adipocyte membranes may be displaced not only from beta-adrenergic receptors but also nonstereospecifically from other membrane compartments by beta-adrenergic and other adrenergic agents. The EC50 of this nonstereospecific displaceable binding is directly related to the liposolubility (n-octanol:water partition coefficient) of the displacing ligand.

Adipose Tissue↗
PubMed1982

The (--)[3H]dihydroalprenolol binding to rat adipocyte membranes: an explanation of curvilinear Scatchard plots and implications for quantitation of beta-adrenergic sites.

In rat adipocyte membranes, both beta-adrenergic agonists and beta-adrenergic antagonists competed with (--)[3H]dihydroalprenolol for high affinity (KD 2-4 nM) and low capacity binding sites. The antagonists but not the agonists competed with (--)[3H]dihydroalprenolol for lower affinity and higher capacity sites. The present studies were performed in order to characterize the adipocyte beta-adrenergic receptor and distinguish it from low affinity, higher capacity sites which were heat-labile and not stereoselective. When isoproterenol was used to define the nonspecific binding, saturation studies showed a single binding site with a capacity of approximately 100 fmol/mg membrane protein (corresponding to approximately 50,000 sites/adipocyte). Binding was saturated by 10 nM (--)[3H]dihydroalprenolol. Approximate KD's of 204 nM were observed. Kinetic analysis of (--)[3H]dihydroalprenolol binding provided an independent measurement of KD between 0.75 and 1.1 nM. This binding site had the characteristics of a beta 1-adrenergic receptor with the potency of isoproterenol greater than norepinephrine greater than or equal to epinephrine as competitors of binding. Furthermore, the KD of inhibition of (--)[3H]dihydroalprenolol binding correlated with the Ki of inhibition by antagonists or Ka of activation by agonists of glycerol release in isolated adipocytes (r = 0.968, P less than 0.001). These results suggest that beta-adrenergic agonists compete with (--)[3H]dihydroalprenolol for the high affinity binding site which represents the physiological site. Furthermore, the use of antagonists (propranolol, alprenolol) to define specific beta-binding includes nonspecific site(s) as well as the beta-adrenergic site. Previous characterization and quantitation of beta receptors in rat fat cell membranes may have been in error by incorporating both types of binding in their measurement.

Adipose Tissue↗
PubMed1981

Quantitation of beta adrenergic receptors in rat liver: confounding effect of displaceable but nonstereospecific antagonist binding.

In rat liver membranes three types of ligand binding were seen using [3H]-dihydroalprenolol (DHA) and [125I]-hydroxybenzylpindolol (HYP): binding stereospecifically displaced by beta-adrenergic agonists and antagonists, binding nonstereospecifically displaced by beta-adrenergic antagonists, and binding which was not displaced by beta-adrenergic agonists or antagonists. The magnitude of the nonstereospecific displaceable binding varied with the physiological state of the animal. It was sufficient to prevent the quantitation of the stereospecific displaceable binding in some preparations from young rats but in all preparations of rats greater than 150 g or more than about 6 weeks of age. In adrenalectomized weanling rats 10-30% of the total binding was of nonstereospecific displaceable type while in control rats it comprised up to 60% of the total binding. Addition of 5 X 10(-6) M phentolamine to the assay eliminated a large proportion of the nonstereospecific displaceable binding. When phentolamine was included in the assay, liver membranes from weanling rats stereospecifically bound 30-35% of total binding; membranes from adrenalectomized rats showed stereospecific binding of up to 50 to 80%. Because the amount of displaceable, nonstereospecific binding varied greatly depending on the physiologic state of the animals, stereospecific displacement should be monitored for every type of liver membrane preparation. Furthermore, animal age is an important variable. Using the published antagonist binding methodology (DHA or HYP) in liver membranes, it is not presently possible to quantitate liver beta-adrenergic receptors in normal rats that have reached maturity.

Adrenal Glands↗
PubMed1981

Mechanism of the age-related decrease of epinephrine-stimulated lipolysis in isolated rat adipocytes: beta-adrenergic receptor binding, adenylate cyclase activity, and cyclic AMP accumulation.

beta-adrenergic binding ([3H]dihydroalprenolol), adenylate cyclase activity, and cAMP accumulation were measured in adipocytes to investigate whether the mechanism of decreased hormone-sensitive lipolytic response with age was mediated through membrane-associated events. The dose of epinephrine required for half maximal stimulation of glycerol release (ED50) was significantly lower in 2-month-old rats (0.8 +/- 0.2 microM)than in matur (6- and 12-month-old) rats (5.2 +/- 1.5 and 6.2 +/- 1.5 microM, respectively). In 24-month-old rats the ED50 (0.7 +/- 0.2 microM) was less than in mature rats. maximum rates of hormone-stimulated glycerol release (per 10(6) cells) was highest in the two mature groups and decreased by 50% in the old rats (P less than 0.01). Lipolytic changes were independent of cell size. beta-adreanergic raeceptor number (50-90 thousand sites/call) and affinity (KD 4-5 nM) were the same in each age group. ED50 and maximum level of hormone-stimulated adenylatae cyclase activity did not change with age. The ED50 of cAMP accumulation of young rats was 3 +/- 5 microM compared with 24 +/- 4 and 25 +/- 5 microM in 6- and 12-month-old rats, respectively. In old rats, the ED50 of cAMP accumulation was 2 +/- 1 microM (P less than 0.001 compared with mature rats). Maximally stimulated cAMP levels were the same in old and mature animals. Phosphodiesterase activity in the presence and absence of 10(-5) M isoproterenol did not change with age. The results suggest that age-related decrease of epinephrine-sensitive lipolysis in old rats may be due to alterations of the lipolytic pathway distal to the receptor-adenylate cyclase complex and the generation of cyclic AMP.

3',5'-Cyclic-AMP Phosphodiesterases↗