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T E Nicholas

Publications and source records attributed to T E Nicholas.

68 records · Page 4Linked to original sources
PubMed1978

The presence in bovine trachealis muscle of cytosol receptors with high affinity for glucocorticoids.

Whereas receptors with high affinity for glucocorticoids have been reported present in both fetal and adult lungs, there has been no attempt to identify such receptors in airways smooth muscle. We have examined the binding characteristics of glucocorticoids for a cytosol fraction prepared from bovine trachealis muscle. The cytosol fraction, which was prepared in 10 mM Tris, 1.5 mM Na2 EDTA and 2 mM dithiothreitol, contained macromolecular high affinity receptors for 3H-dexamethasone (Kd = 5.6 nM) at a concentration of 0.20 pmol/mg protein. The comparative affinities of other steroids in descending order were: beclomethasone-17, 21-dipropionate, dexamethasone, beta-methasone, triamcinolone and triamcinolone acetonide. Progesterone and deoxycorticosterone only bound to a limited extent, whereas the binding with 5 alpha-dihydrotesterone and pregnenolone was negligible. We conclude that airways smooth muscle is a target tissue for glucocorticoids and postulate that the binding of glucocorticoids to these receptors may receptors may represent the initial step in the anti-asthmatic action of these drugs.

Animals↗
PubMed1975

The metabolism of 3-H-cortisone and 3-H-cortisol by the isolated perfused rat and guinea pig lungs.

Isolated perfused rat lungs removed more than 35% of 3-H-cortisone (1 times 10-9M) from the perfusate during one passage through the pulmonary circulation. The cortisone in the lungs was then rapidly converted to cortisol, which was returned to the perfusate. The tritiated steroid taken up was so rapidly washed from the lung, that only 10% remained after a 12 minute perfusion with steroid-free medium. In recirculating experiments, nearly 60% conversion to cortisol occurred over 32 cycles; in addition, there was a slow increase in the percentage of polar compounds in the medium. Similarly, the perfused hindlimbs preparation from the rat converted cortisone to cortisol and returned the cortisol to the perfusate. In contrast, guinea pig isolated perfused lungs had neglible effect on cortisone. Rat lungs demonstrated only a limited ability to convert 3-H-cortisol to cortisone. The results suggest that the lungs may play an important role in maintaining cortisone/cortisol levels in the plasma.

Animals↗
PubMed1971

Responses of mean arterial pressure to pressor agents and diuretics in renal hypertensive and salt hypertensive rats.

1. The responses of the mean arterial pressure to (-)-noradrenaline, tyramine, angiotensin II-val(5)-amide, vasopressin and rat renin have been contrasted in renal hypertensive and in salt plus desoxycorticosterone hypertensive rats. The responses were measured in rats both unanaesthetized and rats anaesthetized with pentobarbitone.2. Responses of unanaesthetized, ganglion blocked renal hypertensive rats to noradrenaline, tyramine and vasopressin markedly exceeded, and to angiotensin II and renin were markedly smaller than, those of unanaesthetized ganglion blocked salt + DOC hypertensive animals. Responses to angiotensin and to renin were apparently enhanced in the latter animals.3. Hydrochlorothiazide and frusemide markedly reduced mean arterial pressure in salt + DOC hypertensive rats before and after ganglionic blockade.4. Neither diuretic caused significant reduction in the mean arterial pressures of unanaesthetized, renal hypertensive rats in the absence of ganglionic blockade: frusemide did so in anaesthetized and unanaesthetized rats after ganglionic blockade.5. Whereas the diuretics did not affect the responses of the renal hypertensive rats to pressor agents, frusemide and to a lesser extent hydrochlorothiazide tended to depress the responses to pressor agents in salt induced hypertension.6. Hydrochlorothiazide did not influence mean arterial pressure in unanaesthetized rats with neurogenic hypertension.

Anesthesia, General↗
PubMedDate not supplied

Immunohistochemical localization and characterization of a rat Clara cell 26-kDa protein (CC26) with similarities to glutathione peroxidase and phospholipase A2.

We have purified and partially sequenced a 26-kDa protein isolated from rat lung lavage. Two-dimensional electrophoresis and Western blotting using an antibody we have raised to this protein indicated that CC26 has 3 isoforms with pIs between 4.9 and 5.5 and is neither a component of surfactant nor present in plasma. The first 10 amino acids of the N-terminal of all 3 isoforms were identical. The first 25 amino acids of the N-terminal sequence were identical to a rat acidic calcium-independent phospholipase A2 and one amino acid different from a mouse nonselenium glutathione peroxidase. Light immunohistochemistry showed a strong reaction with the airway hypophase from the trachea down to the terminal bronchioles, but not in the alveolus. Immunohistochemistry at the electron microscopy level showed that CC26 was localized to the dense secretory bodies and endoplasmic reticulum of the Clara cell and secretory granules of tracheal nonciliated serous and goblet cells. Heavily labeled Clara cell dense secretory bodies were observed in the process of being exocytosed. Biochemical and further sequence analysis will be required to determine if this protein is either a nonselenium glutathione peroxidase or a calcium-independent phospholipase A2.

Amino Acid Sequence↗
PubMedDate not supplied

Body temperature alters the lipid composition of pulmonary surfactant in the lizard Ctenophorus nuchalis.

In any 24-h period the body temperature (Tb) of the central Australian agamid lizard, Ctenophorus nuchalis, may vary from 13 to 45 degrees C; the mean preferred Tb is 37 degrees C. We have analyzed surfactant-type lipids in lizards that underwent rapid changes in Tb from 37 degrees C to 14, 19, 27, or 44 degrees C. Lipids were extracted from lung lavage and lamellar body fractions, and phospholipids and cholesterol components were measured. There was no change in either the total amount or relative proportions of the different classes of phospholipids, but cooling increased the cholesterol content of lavage. An increase in the cholesterol: phospholipid ratio was evident within 2 h of cooling to 19 degrees C and was maintained for at least 48 h. The ratio increased from 8% at 37 degrees C, to 15% after 4 h at 19 degrees C, and 18% after 4 h at 14 degrees C. Possibly the increase in cholesterol promotes fluidity and absorption of surfactant within the alveoli of lizards with low Tb. Cold lizards collapse their lungs during prolonged periods of apnea and the surfactant may prevent the epithelial walls from adhering.

Animals↗
PubMedDate not supplied

Effect of hyperpnea on the cholesterol to disaturated phospholipid ratio in alveolar surfactant of rats.

Hyperpnea induced by swimming rats for 30 min decreased the cholesterol/disaturated phospholipid ratio (CHOL/DSP) in the tubular myelin-poor fraction (alv-2), but did not affect the tubular myelin-rich fraction (alv-1). The phenomenon was further illustrated by the marked inverse relationship between CHOL/DSP and DSP. Because such a result could reflect differential release, processing, or reuptake within the alveolar compartment, this study further explored the mechanism in the rat isolated perfused lung (IPL), using radiolabeled CHOL (3H) and DSP (14C). The study also examined whether the decrease in CHOL/DSP with swimming was associated with the increase in either tidal volume (VT), frequency of breathing (f), or both. It was found that whereas a 2.5-fold increase in VT for 15 min in the IPL increased the CHOL/DSP in alv-1 and decreased it in alv-2, a 3-fold increase in f markedly increased the CHOL/DSP in both alveolar subfractions. In apparent contrast, the increases in both VT and f markedly depressed the ratio of the sp act of CHOL/DSP, reflecting a large decrease in the sp act of CHOL in the alveolar compartment. In view of the acute nature of these IPL experiments, it is suggested that the changes reflect the differential release of CHOL and DSP. Furthermore, the marked decrease in sp act of CHOL must reflect a second source of CHOL supplying the alveolar compartment with sterol of low sp act. It is concluded that there is differential handling of surfactant CHOL and DSP in the alveolar compartment of the rat and that the decrease in CHOL/DSP with swimming is due to an increase in VT.

Animals↗