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E Goulding

Publications and source records attributed to E Goulding.

6 recordsLinked to original sources
PubMed1994

Potassium channel inactivation peptide blocks cyclic nucleotide-gated channels by binding to the conserved pore domain.

Cyclic nucleotide-gated (CNG) channels in photoreceptors and olfactory neurons are activated by intracellular ligands (cAMP and cGMP) rather than voltage. Surprisingly, these channels share amino acid sequence homology with voltage-gated channels. Here we show that the distinct gating mechanisms exhibited by CNG and voltage-gated channels share features that reflect this structural homology. Thus, a 20 amino acid peptide ("ball peptide") derived from the Shaker-type K+ channel and responsible for its rapid inactivation also blocks CNG channels. Moreover, the peptide selectively blocks open CNG channels and prevents channel closure, showing that CNG channel activation, like activation of voltage-dependent K+ channels, involves the opening of a gate located on the intracellular side of the peptide-binding site. Amino acid substitutions in the peptide cause similar changes in blocking affinity of CNG and K+ channels, suggesting a conserved binding site. Using a chimeric retinal/olfactory channel, we show that the difference in the peptide affinity of the two CNG channels is due to a difference in the amino acid sequence of the conserved pore-forming region, demonstrating that this domain forms part of the peptide receptor.

Animals↗
PubMed1993

Could you be a 'buddy'?

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Acquired Immunodeficiency Syndrome↗
PubMed1983

In vitro exposure of male and female mice gametes to cadmium chloride during the fertilization process, and its effects on pregnancy outcome.

The effect of cadmium chloride (Cd) on gamete fusion in vitro was evaluated, with further observations of the embryonic development and assessment of the pregnancy outcome of the in vitro fertilized mice. Oocytes were recovered from superovulated B6C3F1 females. Of 1210 control oocytes, 53.2% cleaved into two-cell stage embryos. Of these, 46.6% developed into blastocyst stage embryos which were then surgically transferred to pseudopregnant female CD-1 mice. Of a total of 63 implanted embryos, 8 (12.7%) developed in utero to live fetuses. Teratological examinations of these "test-tube" mice revealed no signs of abnormalities caused by in vitro culture. Male and female gametes were exposed to 0.4, 0.8, or 1.6 microM of Cd and a decrease in sperm motility was noted in the 1.6 microM group. Nevertheless, even in the highest concentration used, 56.4% of the ova cleaved into the two-cell stage, thus indicating no effect of Cd on initial gamete interaction. Gametes that had been treated with 0.4 and 0.8 microM Cd developed to blastocysts at rates comparable to that of the controls. In the 1.6 microM group, however, only one (3.2%) of the two-cell embryos developed to the blastocyst stage. Blastocysts from 0.4 microM Cd-treated gametes were then transferred to surrogate dams. Statistically significant blastocyst losses were recorded during the implantation period, whereas the pregnancy rate and the numbers of resorbed and live fetuses, were comparable to those of the controls. The offspring exhibited no malformations, and their body weights remained within the control values.

Animals↗
PubMed1981

Assessment of the teratogenic potential of acrolein and cyclophosphamide in a rat embryo culture system.

Rat conceptuses were explanted from the uterus on day 10.5 of gestation. The embryos within the yolk-sacs were then transferred to culture bottles containing pure male rat serum either with or without liver microsomes and NADPH. Acrolein (AC), present worldwide in the environment and one of the intermediate metabolites of cyclophosphamide (CPA), was added to these culture mediums. The conceptuses were grown for a period of 48 h after which the morphological features and their degree of differentiation were examined and the DNA and protein contents determined. The effects produced by AC were compared with those obtained by CPA treatment, using the same culture conditions. AC treated embryos and yolk-sacs showed slight but statistically significant inhibition of growth at concentrations of 100 microM and 150 microM. Higher dose levels (200 microM and 250 microM) resulted in a drastic inhibition of growth and differentiation. However, no gross structural defects were observed at the dose-levels used. In contrast, conceptuses cultivated in the presence of CPA (350 microM), liver microsomes and NADPH showed characteristic morphologic lesions. Our findings indicate that AC is lethal to embryos within a narrow dose-range, but has no teratogenic potential. Therefore, AC is not the metabolite which is responsible for the teratogenic effects observed after CPA treatment in vivo. The results also demonstrate that the postimplantation embryo culture system can discriminate between embryolethal and teratogenic effects and that whole embryos in culture can respond to teratogens in a manner similar to embryos exposed in vivo.

Abnormalities, Drug-Induced↗