I. L. Schwartz

Leucylglycinamide Released from Oxytocin by Human Uterine Enzyme

Uteri of pregnant and nonpregnant women contain enzymic activities which inactivate oxytocin. A potent enzyme, which has been partially purified from uterine homogenates, cleaves the prolyl-leucyl peptide bond of oxytocin. This findinig associates for the first time the release of the dipeptide leucylglycinamide with the degradation of neurohypophyseal hormones.

Distribution of parathyroid hormone-stimulated adenylate cyclase in plasma membranes of cells of the kidney cortex

SummaryFree flow electrophoresis was employed to separate renal cortical plasma membranes into luminal (brush border microvilli) and contraluminal (basal-lateral membrane) fractions. During the separation adenylate cyclase activity was found to parallel the activity of Na+−K+-activated ATPase, an enzyme which is present in contraluminal but not in luminal membranes. In the basal-lateral membrane fraction the specific activities of adenylate cyclase and Na+−K+-activated ATPase were 4.4 and 4.6 times greater, respectively, than in the brush border fraction.The adenylate cyclase of the basal-lateral membrane fraction was specifically stimulated by parathyroid hormone which maximally increased enzyme activity eightfold. The biologically active (1–34) peptide fragment of parathyroid hormone produced a 350% increase in adenylate cyclase activity. In contrast, calcitonin, epinephrine and vasopressin maximally stimulated the enzyme by only 55, 35 and 30%, respectively.These results indicate that adenylate cyclase, specifically stimulated by parathyroid hormone, is distributed preferentially in the contraluminal region of the plasma membrane of renal cortical epithelial cells.

Complete amino acid sequence of bovine neurophysin II

Abstract The complete amino acid sequence of bovine neurophysin II, a 97 amino acid protein which specifically binds the posterior pituitary hormones oxytocin and arginine vasopressin, is proposed.

Chemistry and structure-activity relations of the antidiuretic hormones

Abstract We have reviewed contributions of synthetic peptide chemistry to several aspects of the biology of the posterior pituitary hormones, and have also indicated how purely biological considerations have stimulated advances in peptide chemistry. It is clear that contributions of such broad, interdisciplinary character can be realized only in a setting of close collaboration between chemists, physiologists and clinicians.

Chromatographic separation of isologous sulfur- and selenium-containing amino acids: Reductive scission of the selenium-selenium bond by mercaptans and selenols

Abstract Racemic Se-methylselenocysteine, selenocystine, selenomethionine, selenoethionine, and Se-benzylselenocysteine are separated from their corresponding sulfur isologs by ion-exchange chromatography. The reason was uncovered for previous failures to obtain reproducible color values for selenocystine. The selenium-selenium bond of selenocystine is cleaved by mercaptans and selenols, yielding acyclic molecules with selenium-sulfur or selenium-selenium bonds. The diselenide-sulfhydryl and diselenide-selenol interchange reactions, which occur over a wide pH range, must be taken into account during analytical investigations involving mixtures of diselenides, and/or thiols, and/or selenols. Treatment of peptides containing selenocystine or selenocysteine residues (1-selenooxytocin, 6-selenooxytocin, deamino-1-selenooxytocin, deamino-6-selenooxytocin and deaminodiselenooxytocin) in 6 N HCl at 110° for 22 hr partially degraded selenocystine; however, when selenocystine itself was treated under identical reaction conditions it was almost entirely destroyed.

Carrier-Mediated Transport Processes

In Chapter 20(1) the movement of solutes across biological membranes is treated in relation to processes which do not, in general, involve a chemical interaction between the permeant and the membrane, and which are thermo-dynamically dissipative in character—i.e., the free energy of the matter under observation decreases during transport.

SOME HISTORICAL HIGHLIGHTS PERTAINING TO THE BIOLOGY OF ANTIDIURETIC HORMONE

Although my assignment for this introductory statement to our session on the actions of antidiuretic hormone is to discuss the development of knowledge in this now complex and wide ranging area, the only realistic approach to this assignment in the time allotted to me is to cite what comes to mind in November 1980 as the highlights of this particular trail of research-and this is essentially what I plan to do in the course of the next nine or ten minutes, even though I am well aware that highlight-spotting is a dangerous game because it is so easy to overlook or forget some significant work and also because it can be such a subjective business-one person’s highlight being another person’s trivia. Nevertheless, because it may have some historical as well as heuristic value I have chosen to play this game, which I do with apologies in advance to all those whom I may have inadvertently or unjustly excluded. The subject of our meeting this afternoon has a venerable history that extends back almost to the turn of the last century when in the same year Farini and von den Velden showed that mammalian posterior-pituitary extracts decreased the rate of urine flow in patients with diabetes insipidus and inhibited water diuresis in normal human subjects. Two decades earlier Ramon y Caja13 had demonstrated for the first time that bundles of nonmyelinated nerve fibers entered the posterior lobe through the pituitary stalk and later studies of P i ~ e s , ~ . Greving,6 and Meyer during the 1920s and 1930s showed the origin of most of these fibers to be cell bodies in the supraoptic and paraventricular nuclei of higher vertebrates 4-6 and the preoptic nuclei of lower vertebrates.7 Not long after the publication of the studies of Pines and Greving the general concept of neurosecretion was developed by Scharrer and Scharrer,s* and Bargmann and associates 10-14 adduced evidence that histologically identifiable neurosecretory material, which contained the neurohypophyseal hormones, is synthesized in the supraoptic and paraventricular nuclei of the hypothalamus in higher vertebrates (and the homologous preoptic nucleus of lower vertebrates) and that this material is transported via the hypothalamo-hypophyseal tracts to the neurohypophysis, which functions solely as a storage center (awaiting the appropriate stimuli that evoke release of the hormones into the bloodstream). In the mid-twenties, at approximately the same time the supraoptic and

Comparison of the mode of action of oxytocin and lysine-vasopressin on the isolated rat uterus.

Ein der Rezeptorentheorie zugrunde liegender Vergleich der Dosis-Wirkungs-Beziehung zwischen Oxytocin und Lysine-vasopressin an der isolierten Rattengebärmutter hat gezeigt, dass während der Evolution die Oktapeptide der Neurohypophyse sowohl ihre Affinität für den Rezeptor als auch ihre maximale Aktivität bei Absättigung des Rezeptors, «intrinsic activity», verändert haben. Weiterhin wurde gefunden, dass Magnesium-Ionen in einer Konzentration von 0.5 mM nicht nur, wie bisher angenommen, die Affinität der Hormone, sondern auch ihre maximale Aktivität bei Absättigung des Rezeptors beeinflussen.

Effects of neurohypophyseal hormones, theophylline and nucleotides on the smooth muscle of the toad bladder

Abstract Neurohypophyseal hormones and their synthetic analogs exhibit both excitatory and relaxing effects on the contractile elements of the urinary bladder of the toad, Bufo marinus . We have interpreted these effects in terms of a dual receptor system in the smooth muscle cells of the bladder. Accordingly, we have determined the potency of several neurohypophyseal hormonal peptides as contractile and relaxing agents and have found, on the one hand, a close correlation between their effects on the contractile responses of the toad bladder and the contractile responses of the rat uterus, and, on the other hand, between their effects on this relaxation of toad bladder smooth muscle and on the increase of transepithelial water flow along an osmotic gradient. The relaxing effect of neurohypophyseal peptides on the smooth muscle of the bladder is mimicked by cyclic 3′, 5′ -AMP, 5′ -AMP, adenosine and theophylline.

Dissipative Transport Processes

The earliest concept of the plasma membrane was that of an ultrathin porous film separating two aqueous solutions in physical as well as in biological systems. In physical systems, use of the porous film model led to the development of the laws of osmotic pressure and to the laws governing the equilibrium distribution of ions across membranes. In biological systems, use of the model has accounted for some, but not for all of the data on distribution and transfer rates of materials across cell membranes. Recent developments have been concerned with the chemical architecture of biological membranes as well as the material transfers across cell membranes.