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R Schwyzer

Publications and source records attributed to R Schwyzer.

At least 55 records · Page 3Linked to original sources
PubMed1980

Effects of ACTH (corticotropin) analogues on steroidogenesis and cyclic AMP in rat adrenocortical cells. Evidence for two different steroidogenically responsive receptors.

Comparative studies on the mechanism of action of ACTH1-39 and ACTH5-24 [corticotropin-(1-39)- and corticotropin-(5-24)-peptides] on isolated rat adrenal cells were performed. The relationship between stimulated steroidogenesis and cyclic AMP was very different, suggesting that cyclic AMP does not play the same role in mediating the action of the two agonists. Data from three separate experiments showed that the competitive antagonist ACTH6-24 [corticotropin-(6-24)-peptide] had mean inhibitor constants of 13.4 +/- 3.1 nM against ACTH1-39 and 3.4 +/- 1.0 nM against ACTH5-24, indicating that the steroidogenic actions of these two agonists are mediated by two different receptor types. We conclude that there are two possible mechanisms for corticotropin action, only one of which involves the necessary production of cyclic AMP.

Adrenal Cortex↗
PubMed1979

Fibrinogen: agreement of experimental and calculated hydrodynamic data with electron-microscopic models.

There is no general agreement on the size and shape of the fibrinogen molecule. We have studied the diffusion of the fibrinogen in solution by means of dynamic light scattering, nanosecond fluorescence depolarization and analytical ultracentrifugation. The results obtained under physiological concentration, pH an ionic strength are DT = 2.0 X 10(7) cm2sec-1, DR perpendicular = 40'000 sec 1. Nanosecond fluorescence depolarization yielded DR parallel = 1.6 x 10(6) sec-1. Tentatively this value is interpreted as DR parallel, namely rotational diffusion about the major axis of the molecule. The sedimentation coefficient is 8.1 S. The hydrodynamic parameters derived from our measurements were compared with those calculated on the basis of the models proposed by Hall and Slayter, Hudry-Clergeon and Marguerie et al., Bachmann and Lederer, and Köppel. The agreement is poor even if the degree of hydration is varied within wide limits. However, satisfactory agreement can be achieved by assuming a flexible molecule of about 900 A length corresponding to two end-to-end bound trinodular structures of the Hall and Slayter type, with a nodule diameter of about 45 A. Experimental evidence indicates that the discrepancies between the different models might be due to different techniques of sample preparation leading to different conformations of the molecule.

Fibrinogen↗
PubMed1979

Capacitance and conductance as tools for the measurement of asymmetric surface potentials and energy barriers of lipid bilayer membranes.

A simple method for determination of asymmetric surface potentials in lipid bilayers is described. The method is based on the dependence of bilayer capacitance on transmembrane voltage. The capacitance is measured by rectifying in 90 degrees component of an applied alternating current signal. A superimposed slow triangular wave results in a hysteresis-like time course of capacitance. The center of the hysteresis figure is shifted along the voltage axis by an amount equal to the difference of the dipole plus surface-charge potentials on the two sides of the bilayer (capacitance minimization potential). Alternatively, such bilayer asymmetry was studied by using the current-voltage characteristics in the presence of nonactin as a carrier. This analysis was based on the integrated Nernst-Planck equation, assuming a trapezoidal energy barrier and equilibrium of the surface reactions. The two methods gave consistent results for the surface potentials of phosphatidyl serine membranes asymmetrically shielded with calcium. In addition, the current analysis yields the positions of the corners of the barrier, found to be set in 13% for this lipid.

Calcium↗
PubMed1978

Studies on polypeptide receptors a critical view on the mechanism of ACTH action.

Recent work on ACTH receptors in adrenal cells and adipocytes is reviewed. It is suggested that ACTH acts on two types of receptor: an adenylate cyclase receptor and another one that helps to guide cAMP into the correct compartment. The introduction of the term holoreceptor to indicate a unit that is recognized by the hormone and is able to produce a measurable effect, and of the terms discriminator, transmitter and effector to indicate the functional subunits of the holoreceptor is suggested as a measure enhancing clarity and flexibility of communication in this very complex field.

Adenylyl Cyclases↗
PubMed1978

Mechanism of alpha-melanotropin action.

A structure-function study of alpha-melanotropin has shown that this tridecapeptide consists of two message sequences, (-Glu)-His-Phe-Arg-Trp- and -Gly-Lys-Pro-Val-NH2, and a potentiator sequence, Ac.Ser-Tyr-Ser-Met-(Glu-), when acting on its melanophore receptors. The key elements of the message, -Phe-Arg- and -Lys-Pro-, do not correspond exactly to those responsible for eliciting the effect in other tissues. It appears that alpha-MSH contains more information than would be necessary to interact with only one complementary receptor site; therefore, the topography of the hormone exposed to the binding site may be different on contact with the receptors of different target cells. To further investigate this aspect, new methods for the isolation and characterization of functional receptors must be developed. We are investigating the use of chemically well-defined, biologically active, covalent hormone-macromolecule complexes for this purpose. Another approach utilizes model receptors with a recognition pattern similar to that of the biological receptor, as described in this communication for certain highly specific antibodies.

Amino Acid Sequence↗
PubMed1977

Purification of bovine adrenal-cortex plasma-membrane vesicles containing a highly corticotropin-sensitive adenylate-cyclase system and angiotensin-II-binding sites.

The purpose of this experimental investigation was to provide a purified plasma membrane fraction containing a highly hormone-responsive adenylate cyclase system. Bovine adrenal cortex was homogenised and a washed pellet (450 000 X g - min) was fractionated by zonal centrifugation in a sucrose and dextran gradient. Adenylate cyclase activity was purified up to 60-fold to a specific activity of 55, 340 and 210 pmol of adenosine 3':5'-monophosphate (cyclic AMP) produced/minute per mg of protein at 38 degrees C for the basal, adrenocorticotrophin and fluoride-activated states, respectively. The time course of the adenylate cyclase activity is linear. The concentration necessary for half-maximal stimulation by adrenocorticotrophin-(1-24)-tetracosipeptide is 0.5 muM. The high hormone-responsiveness of the membrane preparation allows one to demonstrate activation of adenylate cyclase by very weakly agonistic adrenocorticotrophin fragments. The F- activated state can be detergent-dispersed by Lubrol and shows a Km (ATP) different from that of either the basal or adrenocorticotrophin-stimulated state. Other marked enzymes such as 5'-nucleotidase, glucose-6-phosphatase and cytochrome oxidase were followed during purification. The plasma membrane fraction shows rather homogeneous, relatively large vesicles (mean diameter 0.5 mum). It contains high-affinity binding sites for angiotensin II (about 2 pmol per mg protein) with an apparent association constant of 2 X 10(7) (1/mol) at 12 degrees C. The yield, 20 mg of membrane protein per preparation, may make it a tool in either affinity-labelling studies with the peptide hormones mentioned or the starting point for solubilisation and purification of adenylate cyclase.

Adenylyl Cyclases↗