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M H Town

Publications and source records attributed to M H Town.

5 recordsLinked to original sources
PubMed1983

Pharmacological and cardiovascular properties of a hydantoin derivative, BW 245 C, with high affinity and selectivity for PGD2 receptors.

Initial experiments demonstrated that the hydantoin prostaglandin derivative, BW 245 C, has potent anti-aggregatory activity on human platelets which may result from its structural similarity with one of the natural prostaglandins. The aim of the present study was to extend this preliminary pharmacological characterization and to determine which, if any, prostaglandin receptor-type is responsible for mediating the biological activity of BW 245 C. A marked species variation was observed in the anti-aggregatory potency of BW 245 C such that in the human (0.36 X PGE1) it was about one hundred times more effective than in the rat (0.003 X PGE1). The relative potencies of PGI2 (ca. 10 X PGE1) and PGE1 were, however, similar in both species. An intravenous bolus injection of 250 micrograms/kg BW 245 C lowered systolic (-23%) and diastolic (-34%) blood pressure in spontaneously hypertensive rats. In radioligand binding studies it showed a high affinity and selectivity for PGD2 platelet receptors, binding to PGI2 or PGE2 receptors was not detectable. Therefore it is concluded that the platelet and cardiovascular actions of BW 245 C are mediated by PGD2 receptors and this accounts for the observed species variation which is a characteristic of this prostaglandin.

Animals↗
PubMed1979

Hydrophobic proteins of lamellated osmiophilic bodies isolated from pig lung.

1. In addition to proteins that are insoluble in organic solvents, lamellated bodies isolated from pig lung and surfactant prepared from bronchopulmonary lavage fluid contain another group of proteins that are extracted together with lipid into the organic phase. 2. These hydrophobic proteins constitute about 40% of the total protein of lamellated bodies and about 13% of the total protein of surfactant isolated from lavage fluid, whereas less than 1% of the total protein of pig lung microsomal fraction and mitochondria is extracted by organic solvents. 3. The hydrophobic proteins of lamellated bodies were separated into four fractions and freed from phospholipid by chromatographic procedures. Their apparent molecular weights vary between 11 500 and 16 500, they contain 72--79% of hydrophobic residues and 16--22% of sulphur-containing amino-acids, and leucine is the major N-terminal amino acid in each case.

Amino Acids↗
PubMed1979

Structural studies on lamellated osmiophilic bodies isolated from pig lung. 31P NMR results and water content.

1. Lamellated osmiophilic bodies are intracellular organelles in which pulmonary surfactant is stored prior to secretion. They contain about 85% phospholipid (per dry weight) and dipalmitoyl phosphatidylcholine is a major constituent, and although their ultrastructure is uncertain it is generally supposed that they resemble liposomes. However, liposomes are stable because layers of water are interposed between the lipid bilayers whereas an essential aspect of the function of lamellated bodies is that, subsequent to their secretion, they are rapidly disrupted to form a surface-active film which covers the respiratory epithelium of the lung. 2. A new method for isolating lamellated bodies from pig lung is described which has the advantage of speed and simplicity and which results in increased yields. The homogeneity of the preparation is similar to that obtained by other methods. 3. 31P NMR spectra of lamellated bodies showed that at 40 degrees C about 95% of the phospholipid was present as extended bilayers and that about 5% was present in a phase exhibiting isotropic head group mobility (tau R less than 10(-5) s). It is suggested that this phase may be due to apolar proteins which are present both in lamellated bodies and in liposomes prepared from lipids extracted from them. 4. The internal water content of lamellated bodies has been measured gravimetrically and the hydration of the phospholipid head groups has been examined by 31P NMR. The two methods gave results in good agreement and show that there are about seven molecules of water/molecule of phospholipid. It is concluded that although the phospholipid head groups in lamellated bodies are fully hydrated, there is no zone of free water. 5. Lamellated bodies are osmotically insensitive to NaCl whereas liposomes prepared from lipids extracted from them behave like perfect osmometers. It is suggested that the osmotic insensitivity and restricted water content of lamellated bodies are important to their function and dependent upon polar proteins in the outer limiting membrane.

Animals↗
PubMedDate not supplied

Prostacyclin-analogs.

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Chemical Phenomena↗