Bromocriptine-induced removal of endoplasmic membranes from prolactinoma cells

Summary Adenomatous prolactin cells lose 39% of their cytoplasm volume within 7 days after the beginning of bromocriptine treatment. A simultaneous reduction of the rough-surfaced endoplasmic reticulum and the Golgi apparatus occurs. Their membranes are removed by rapid transport along the secretory pathway to the cell surface and to lysosomal destruction.We thank Prof. E. del Pozo, Sandoz Ltd, Basle, for the generous gift of injectable bromocriptine, Prof. E.R. Weibel, Dept. of Anatomy, University of Bern, for his technical advice, Dr U. Helfenstein, Institute of Biostatistics, University of Zürich, for his help in the statistical evaluation of the results and the EMDO-Foundation, Zürich, for financial support.     

Selective protection of cells against X-irradiation. Isoproterenol protects only those cells that possesβ-adrenoreceptors

Summary In mixed culture of Chinese hamster fibroblatst, clone 431, and transformed murine L fibroblasts, clone B-82, isoproterenol was found to protect only 431 cells against ionizing radiation. It was shown that 431 cells, in contrast to B-82 cells, possess-adrenoreceptors, and the radioprotective effect of isoproterenol can be realized only if this agent interacts with-adrenoreceptors coupled with the cAMP system. Since malignization often causes the disappearance of-adrenergic and other hormone receptors, the combined culturing and irradiation of the cells studied can be regarded as a model of the growth of malignant cells (B-82) among normal tissue cells (431 cells) under conditions of radiation therapy. A possibility of selective protection against radiation damage of normal tissue cells, with retention of the former radiosensitivity of tumor cells, is discussed.     

AnAnolis skin melanophore assay suitable for photoaffinity labeling studies with α-MSH

Summary Visual determination of MSH-induced pigment migration in melanophores of small pieces ofAnolis carolinensis skin is standardized by first measuring photoelectrometrically the change in reflection/transmission of the whole dorsal skin in response to different hormone concentrations. This method allows the rapid and precise recording of time-response curves after photoaffinity labeling of MSH receptors or of dose-response curves of large series of synthetic compounds.Acknowledgments. We wish to thank Ms V. Jäggin, Ms C. Schulthess and Ms G. van Hees for excellent technical assistance, Dr. R. Andreatta, Ciba-Geigy AG, Basel, for his generous gift of -MSH and Prof. A Pletscher for his continuous interest. This work was supported by the Swiss National Science Foundation.     

Bicuculline and picrotoxin block γ-aminobutryic acid-gated Cl− conductance by different mechanisms

Summary Using isolated, internally perfused bullfrog dorsal root ganglion cells we have studied the dose-response curves for -aminobutyric acid (GABA) in the presence of internally or externally applied GABA antagonists. With external application of antagonists the inhibition of the GABA current by bicuculline was competitive and that by picrotoxin was noncompetitive. Picrotoxin but not bicuculline blocked when internally perfused.To whom reprint requests should be addressed.Acknowledgments. We thank Drs S. Minakami and S. Yasui for helpful discussions and comments.     

Quantitative genetic models of sexual selection

Summary Quantitative genetic models of sexual selection have disporven some of the central tenets of both the handicap mechanism and the sexy son hypothesis. These results suggest that the good genes approach to sexual selection may generally lead to erroneous results.Runaway sexual selection seems possible under a wide variety of circumstances. Quantittive genetic models have revealed runaway processes for sexually selected attributes expressed in both sexes and for attributes of parental care. Furthermore, the runaway could occur simultaneously in a series of populations that straddle an environmental gradient. While the models support the feasibility of runaway processes, empirical studies are needed to evaluate whether runaways actually happen. Estimates of critical genetic parameters are particularly needed, as well as measures of natural and sexual selection acting on the same population.The models also show that sexual selection has tremendous potential to produce population differentiation, particularly in epigamic traits. Differentiation is promoted by indeterminancy of evolutionary outcome, transient differences among populations during the final slow approach to equilibrium, sampling drift among equilibrium populations, and the tendency of sexual selection to amplify geographic variation arising from spatial differences in natural selection. Recent work with two- and three-locus models of sexual selection has produced results that parallel the results of the polygenic models^36–38,58. Thus the feature of indeterminate equilibria (outcome dependent on initial conditions) is common to both types of model.     

A new semisynthetic ergot peptide alkaloid: DCN 203-922

Summary We report the synthesis, stereochemistry and preliminary pharmacological evaluation of DCN 203-922, a novel ergot alkaloid of the cyclol type, which contains in its peptide moiety the uncommon amino acid L-allo-isoleucine.Part of this paper was reported by this author at the Herbstversammlung der Schweizerischen Chemischen Gesellschaft, Bern, in October 1986.     

Cell-to-cell coupling studied in isolated ventricular cell pairs

Summary Cell pairs isolated from adult rat and guinea pig ventricles were used to study the electrical properties of the nexal membrane. Each cell of a pair was connected to a voltage-clamp system so as to enable whole-cell, tight-seal recording. The current-voltage relationship of the nexal membrane was found to be linear, revealing a resistance r_n of 2–4 M. r_n was insensitive to the sarcolemmal membrane potential (range:–90 to +30 mV), and exerted no time-dependent gating behavior (range: 0.1 to 10 s). Lowering pH_i yielded a small increase in r_n. Vigorous elevations in [Ca²⁺]_i gave rise to an increase in r_n which was associated with a cell shortening. Uncoupling caused by aliphatic alcohols or halothane did not produce cell shortening. Cell pairs were also used to study action potential transfer.     

A major metabolite of Δ1-tetrahydrocannabinol reduces its cataleptic effect in mice

Summary The results described here demonstrate that THC-induced catalepsy in mice can be substantially inhibited by the prior administration of ¹-THC-7-oic acid, the major metabolite of THC in most species including humans. This raises the possibility that the intensity and duration of action of THC may depend to a large degree on the levels of this metabolite at the sites of action.We thank the National Institute on Drug Abuse for supporting this project by grants DA-02043 and DA-02052 and for supplying all of the cannabinoids. One of us (S.B.) is also the recipient of a Research Scientist Award from NIDA. We are grateful to Kristen Carlson and Thomas Honeyman for helpful suggestions in preparing this report.