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Biomedical subjects

S R Shaw

Publications and source records attributed to S R Shaw.

54 records · Page 3Linked to original sources
PubMed1977

The fate of prostaglandin A1-5,6-3H in the rat.

The plasma concentrations, tissue distribution and excretion of prostaglandin A1 (PGA1) and related metabolites have been determined in rats, following the intravenous injection of a single dose of PGA1-5,6-3H. Urinary and faecal excretion accounted for averages of 25 and 43% of the administered dose of PGA1, respectively. Oxidative cleavage of the carboxyl side chain of PGA1 appeared to be a major metabolic pathway in the rat. PGA1-5,6-3H was deemed unsuitable for metabolism studies in man, in view of the significant loss of tritium label from the prostaglandin;

Animals↗
PubMed1972

Decremental conduction of the visual signal in barnacle lateral eye.

1. There are problems associated with the notion that slow potentials alone are used to transmit information in the early stages of some visual systems. This idea and alternatives have been tested on the barnacle lateral ocellus, a simple eye with only three photoreceptors, each with its own axon about 1 cm long.2. All of the receptors have very similar properties including spectral sensitivity, and are also electrically coupled together. Impulses cannot be recorded from any of the cell bodies, all of which have been impaled as shown by dye marking.3. No impulses can be recorded externally from most of the ocellar nerve or intracellularly from the receptor axon terminals. Impulses driven by light, sometimes recorded in the final part of the nerve, are believed to originate in other axons.4. During illumination of the eye, current enters the receptor soma and leaves via the rest of the axon. This is consistent with the idea that the axon acts as a purely passive cable. The passive behaviour was also demonstrated in a comparison of the relative attenuation down the axon, of hyperpolarizations and depolarizations.5. Calculations based on the supposed electrical constants of the somas showed that the slow potential itself was unlikely to be the visual signal, since it would be enormously attenuated by passive spread down the long thin axons. To check this, the axon terminals in the supraoesophageal ganglion were penetrated and identified by electrical and dye-marking criteria. In fact, the slow potential was attenuated in the most favourable case only by a factor of about three, indicating an axon membrane resistance in the range of 10(5) Omega. cm(2).6. This resistance may be substantially higher than that of the soma surface membrane, corrected for increased surface area. The sheath around each axon probably does not influence the electrical properties, judged by its permeability to the small molecule of Procion Yellow.7. The minimal loss of voltage in the axon and the absence of regenerative activity implicate the slow potential itself as the visual signal. But there remains the alternative that light triggers some unknown transmission process, of which the slow potential is only an incidental by-product. If this were so, artificially imposed changes of membrane potential should not duplicate the action of light in promoting synaptic transmission. To test this, receptors were polarized by currents through the pipette whilst visually driven post-synaptic cells in the oesophageal connectives were being monitored. Currents could effectively substitute for lights to produce post-synaptic impulse trains of similar form and latency, confirming that the potential change produced by light is the normal visual signal.8. Only increases of receptor membrane potential stimulate the particular post-synaptic axons examined, which give ;off' responses to light. Transmission from the receptors is a voltage-dependent process which is most sensitive when a receptor is hyperpolarized from an already depolarized level.9. The discrimination of small visual signals from intrinsic axon noise is discussed, and should pose no problem in the case of the barnacle, where the smallest effective signal measured was about 0.3 mV in the soma. In other eyes where the problem may be more severe, electrical junctions between receptors could significantly improve the signal/noise ratio.

Action Potentials↗
PubMedDate not supplied

Absorption, tissue distribution, and excretion of 3H-labeled arbaprostil in the male rat.

A single dose of arbaprostil-11 beta-3H (4 micrograms/kg) was administered orally to male rats. A maximum plasma radioactivity concentration equivalent to 2.5 to 2.8 nanograms of the prostaglandin per ml was reached at 30 minutes and was maintained until 120 minutes after drug administration. The plasma drug disappearance half-life was 2.6 hours. These results along with data from tissue distribution studies suggested a rapid uptake of radiolabeled arbaprostil by the glandular stomach tissue followed by an apparent zero-order release of drug-related radioactivity from this tissue "reservoir" into the plasma. Drug-related radioactivity was excreted rapidly, with 96 to 99% of the urinary excretion and 82 to 97% of the fecal excretion being completed within 24 hours. A total of 49.6 +/- 3.5% of the orally administered dose was excreted in the urine and 46.7 +/- 3.9% in the feces. No radioactive residues were detected in the animals at the end of the 120 hour specimen collection period. The metabolic stability of the 11 beta-tritium label and the suitability of arbaprostil-3H for use in human studies was demonstrated.

Absorption↗
PubMedDate not supplied

Isolation and characterization of urinary metabolites of arbaprostil in the rat.

The urinary metabolites of arbaprostil-3H in the male rat were profiled, isolated, and purified. Their structures were deduced by gas chromatography/mass spectrometry (GC/MS) studies after conversion to the methyl ester-methoxime-trimethylsilyl ether derivatives, aided by GC with simultaneous radioactivity monitoring. The identified metabolites accounted for over 91% of the urinary excretion products. beta-oxidation of the carboxy side-chain of arbaprostil to 15-methyl-tetranor PGE1 appeared to be the most significant metabolic pathway. Conversion to the dinor A and B derivatives and further beta-oxidation of these to the 15-methyl-tetranor A and B metabolites also appeared to occur. C-19-hydroxylated tetranor A and B derivatives of arbaprostil-3H were excreted in the urine. No conjugated urinary metabolites were evident.

Animals↗
PubMedDate not supplied

Isolation and characterization of the urinary metabolites of arbaprostil in the male dog after intravenous administration.

The profile of urinary metabolites of 3H-arbaprostil was characterized in the male dog after intravenous administration. The major metabolites were purified and their structures deduced by gas chromatography/mass spectrometry (GC/MS) studies after conversion to the methyl ester-methoxime-trimethylsilyl ether derivatives, aided by GC with simultaneous radioactivity monitoring. The identified metabolites accounted for 96% of the urinary excretion products. beta-Oxidation of the carboxy side-chain of arbaprostil to 15-methyl-2,3,4,5-tetranor PGE1, via the 15-methyl-2,3-dinor PGE2 intermediate, appeared to be the most significant metabolic pathway. In contrast to the rat, the following were observed in the dog: glucuronic acid conjugation of the 15-methyl-2,3,4,5-tetranor PGE, and PGA metabolites; detection of the 15-methyl-2,3-dinor PGE2 intermediate; absence of 19-hydroxyl-15-methyl-2,3,4,5-tetranor PGA, and PGB metabolites; oxidation at C-20; and excretion of some parent drug.

Administration, Oral↗