Research Article
Abstract
We used ultrastructural morphometric methods to study the in vivo regulation of secretion in bronchiolar Clara cells of rats. The Clara cells studied were located in airways with an internal diameter of 0.21 +/- 0.06 mm (mean +/- SD) at a transpulmonary pressure of 20 cm H2O. We found that pilocarpine caused a 50% decrease in the volume density of secretory granules of Clara cells in 60 min and that atropine blocked this effect. Isoproterenol produced a similar fall in volume density and this was blocked by propranolol. Propranolol also blocked the effect of pilocarpine. The fall in volume density of the secretory granules produced by pilocarpine and by isoproterenol occurred without any change in the surface-to-volume ratio of the granules. This indicates the change in volume density reflected a decrease in number rather than in size of the secretory granules. The observation that propranolol blocks the secretory response to pilocarpine as well as the response to isoproterenol suggests a dual in series cholinergic adrenergic regulation of secretion in bronchiolar Clara cells in rats.
Authors
G D Massaro, M Paris, L A Thet
Abstract
The ability of the neutrophil myeloperoxidase-hydrogen peroxide-halide system to induce the release of human platelet constituents was examined. Both lytic and nonlytic effects on platelets were assessed by comparison of the simultaneously measured release of a dense-granule marker, [3H]serotonin, and a cytoplasmic marker, [14C]adenine. Incubation of platelets with H2O2 alone (20 μM H2O2 for 10 min) resulted in a small, although significant, release of both serotonin and adenine, suggesting some platelet lysis. Substantial release of these markers was observed only with increased H2O2 concentrations (>0.1 mM) or prolonged incubation (1-2 h).
Authors
Robert A. Clark
Abstract
The mechanisms responsible for altered adrenergic tone in hyperthyroidism and hypothyroidism are not fully understood. To investigate these mechanisms, the β-adrenergic receptor-cyclic AMP complex of the turkey erythrocyte was studied among groups of normal, hyperthyroid, and hypothyroid turkeys. In erythrocytes obtained from hypothyroid turkeys, there were fewer β-adrenergic receptors than in normal cells as determined by the specific binding of [125I]iodohydroxybenzylpindolol, as well as associated decreases both in catecholamine-responsive adenylate cyclase activity and in cellular cyclic AMP content. In contrast, erythrocytes obtained from hyperthyroid turkeys contained the same number of β-receptors and had the same catecholamine-responsive adenylate cyclase activity as cells from normal birds. Other characteristics of the β-receptors in cells from hyperthyroid birds were indistinguishable from those present in normal erythrocytes. However, within the range of circulating catecholamine concentrations, 5-50 nM, the erythrocytes of the hyperthyroid turkeys generated substantially more cyclic AMP after exposure to isoproterenol than did normal cells. These results suggest that thyroid hormone affects β-receptor-cyclic AMP interrelationships in the turkey erythrocyte by two distinct mechanisms: (a) In hypothyroidism, both β-receptors and catecholamine-dependent cyclic AMP formation are coordinately decreased; (b) in hyperthyroidism, β-receptors are unchanged but there is an amplification of the hormonal signal so that occupation of a given number of receptors at physiological concentrations of catecholamines leads to increased levels of cyclic AMP.
Authors
John P. Bilezikian, John N. Loeb, Donald E. Gammon
Abstract
Reports by a number of investigators have described the thymus-derived (T)-cell dependence of immunoglobulin synthesis by pokeweed mitogen (PWM) stimulated human peripheral blood bone marrow-derived (B) cells. Because of the cooperative nature of this in vitro system, it was chosen for examination of the differential effects of low density lipoprotein inhibitor (LDL-In) on B- and T-cell functions. Supernates from 7-d cultures that contained either peripheral blood mononuclear cells (PBM) or combinations of isolated lymphocyte populations were assayed for immunoglobulin (Ig)G by competitive inhibition radio-immunoassay. LDL-In suppression of whole PBM IgG synthesis occurred at 5-20 μg protein/ml and was independent of PWM concentration. Maximal suppression required preincubation of cells with LDL-In before stimulation. Suppression was also observed when B cells alone were exposed for 24 h to LDL-In before PWM stimulation; these suppressed B cells were not rescued by normal T cells. Exposure of T cells alone to low doses of LDL-In for 24 h augmented, but high doses suppressed, IgG synthesis, suggesting a differential effect on T-helper vs T-suppressor cell populations. Independent LDL-In exposure of T-helper or T-suppressor cell enriched populations, separated by rosetting with IgG- or IgM-coated ox erythrocytes, identified the T-suppressor cell populations as the most sensitive of the lymphocyte populations tested. The sensitivities of lymphocyte subpopulations to LDL-In, relative to PBM, were 2.8, 1.2, and 0.3 for the T-suppressor cells, B cells and T-helper cells, respectively. Thus, both B and T lymphocytes are sensitive to and can be regulated by LDL-In. In addition, the biologic activity observed when unseparated PBM are exposed to LDL-In appears to represent a composite of the sensitivity of each of the lymphocyte subpopulations.
Authors
Linda K. Curtiss, Thomas S. Edgington
Abstract
In vitro studies of isolated, perfused, cortical collecting tubules have demonstrated that prior chronic deoxycorticosterone acetate (DOCA) treatment increases sodium reabsorption in this nephron segment, yet sodium balance in vivo is maintained. To evaluate the effect of chronic DOCA treatment on collecting duct sodium reabsorption in vivo, we compared fractional sodium delivery (FDNa%) out of the superficial late distal tubule with the fraction of sodium remaining at the base and the tip of the papillary collecting duct during extracellular fluid volume expansion in untreated, salt-treated, and DOCA-salt-treated rats. In untreated rats, FDNa% to the distal tubule was 6.5±1.0%, and to the base was 8.7±1.6% (Δ2.2±0.9%, P < 0.05). FDNa% to the tip was 4.9±1.1%, significantly less than FDNa% to the base (Δ3.7±1.1%, P < 0.01). In salt-treated rats, FDNa% to the distal tubule was 8.3±0.8%, and to the base was 10.4±1.1%. FDNa% to the tip was 5.9±0.6%, significantly less than FDNa% to the base (Δ 4.6±1.0%, P < 0.005). In DOCA-salt-treated rats, FDNa% to the distal tubule was 16.1±2.6% and to the base was 9.5±1.9% (Δ 6.6±1.7%, P < 0.005). FDNa% to the tip was 5.9±1.2%, also significantly less than FDNa% to the base (Δ 3.6±1.1%, P < 0.01). We conclude that (a) in DOCA-salt-treated rats, sodium delivery to the end of the superficial distal tubule is greater than in untreated or salt-treated rats; (b) in DOCA-salt-treated rats, sodium delivery to the end of the superficial distal tubule is greater than to the base of the papillary collecting duct, suggesting stimulation of sodium reabsorption in the cortical and(or) outer medullary collecting duct; and (c) sodium reabsorption by the papillary collecting duct is unaffected by chronic DOCA-salt treatment in the volume-expanded rat.
Authors
John A. Haas, Theresa J. Berndt, Stephen P. Youngberg, Franklyn G. Knox
Abstract
Prostacyclin (PGI2) is the most potent, naturally occurring inhibitor of platelet aggregation known. To determine whether PGI2 is bound by platelets, high specific activity [9-3H]PGI2 was synthesized by iodination and subsequent base treatment of the labeled precursor [9-3H]prostaglandin (PG)F2α methyl ester. Binding experiments were performed at room temperature with normal citrated human platelet-rich plasma that contained [14C]sucrose or [14C]PGF1α as an internal marker for the extracellular space. Binding of [3H]PGI2 plateaued within 2 min and this bond radioactivity could be displaced rapidly by excess nonradioactive PGI2. Scatchard analysis of concentration-dependent binding yielded a hyperbolic plot which appeared to be caused by the existence of two classes of binding sites. The higher affinity class has a dissociation constant of 12.1±2.7 nM and a capacity of 93 (±21)sites per platelet. The lower affinity class had a dissociation constant of 0.909±.236 μM and a capacity of 2,700±700 sites per platelet. The relative ability of PGI2, PGE1, PGE2, and 6-keto-PGF1α to displace [3H]PGI2 initially bound to the higher affinity class of sites were 100:5:<0.3: <0.3. These relative abilities parallel the relative potencies of these compounds as inhibitors of ADP-induced platelet aggregation in vitro. However PGD2, which is more potent than PGE1 as an inhibitor of aggregation, did not displace bound [3H]PGI2. The higher affinity binding site for PGI2 appears to be the specific receptor through which PGI2 exerts its effect on platelets.
Authors
Adelaide M. Siegl, J. Bryan Smith, Melvin J. Silver
Abstract
Adipocyte size and number were determined in 288 subjects ranging in age from 4 mo to 19 yr. The study was performed in 110 obese and 178 non-obese subjects. 4-yr, longitudinal, follow-up studies were also performed in 132 subjects. The results demonstrate that the contribution of cell number and size to the growth of the fat depot in nonobese children varies with age. Deviations from this normal development were observed in obese children shortly after 1 yr of age. By 11 yr of age obese children exceeded the mean cell number found in nonobese adults. Indeed, obese subjects displayed more rapid and earlier elevations in both cell number and size, which were maintained throughout the study. Thus obese children display both quantitative and qualitative differences in fat tissue development when compared to nonobese children. The data indicate that the rate and type of adipose tissue cellular development one encounters in children may play a role in the development of the enlarged fat depots found in obese subjects.
Authors
J L Knittle, K Timmers, F Ginsberg-Fellner, R E Brown, D P Katz
Abstract
Recent work suggests the existence of a dual corticosteroid feedback mechanism of stress-induced ACTH secretion in the rat. This possibility led us to study the kinetics of suppression of ACTH levels by corticosteroid administration in patients with nonstress ACTH hypersecretion secondary to hypoadrenocorticism. Cortisol was administered according to different protocols, which were chosen to provide extreme variations of the input signal. By this means, two phases of suppression of ACTH levels could be differentiated. A first decrease occurred without latency whenever, and as long as, plasma cortisol levels were rising. There was a linear regression between the logarithm of the increments in cortisol concentrations and the decrease in ACTH levels per minute (r = 0.951) (differential or rate-sensitive feedback mechanism). Neither the absolute doses of cortisol, nor plasma cortisol concentrations were closely correlated with the degree of suppression of ACTH by this rapid mechanism. A second decrease in ACTH levels began ≅30 min after corticosteroid administration. In this case there was a significant linear regression between the degree of inhibition of ACTH levels and the cortisol doses (r = 0.997) (integral or dose-sensitive feedback mechanism).
Authors
H. L. Fehm, K. H. Voigt, G. Kummer, R. Lang, E. F. Pfeiffer
Abstract
The influence of testosterone on gonadotropin-releasing hormone (GnRH) secretion was assessed indirectly by altering the serum testosterone concentration of male rats and measuring GnRH release from their incubated hypothalami 1 wk later.
Authors
Robert S. Rudenstein, Homayoon Bigdeli, Maureen H. McDonald, Peter J. Snyder
Abstract
A further study of the Tgamma-chain in a variety of conditions has revealed its presence in the cord bloods of ethnic groups previously unstudied. Heterozygous newborn average 17-19% Tgamma-chain while the mean value in four presumed homozygotes was 31%. The Tgamma-chain is readily detectable in beta-thalassemia of various ethnic groups (although infrequent in Blacks) as well as in deltabeta-thalassemia. Studies of a few families have provided an opportunity to determine whether or not certain individuals are heterozygous or homozygous for the Tgamma-gene. The Tgamma-chain has not been detected in the human fetal hemoglobin that is synthesized in increased amounts in persons with the hereditary persistence of fetal hemoglobin. Although the Tgamma-chain is detectable in sickle cell anemia, its frequency appears to be lower than in normal individuals. By focusing upon the relationship of the percentage of Tgamma-chain to the sources of human fetal globulin from determinants in cis and in trans, the conclusion has been reached that the Tgamma-chain is the product of a mutant Agamma-locus which should be named the TAgamma-chain.
Authors
W A Schroeder, T H Huisman, G D Efremov, J R Shelton, J B Shelton, R Phillips, A Reese, M Gravely, J M Harrison, H Lam
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