Showing papers in "Physiological Reviews in 1979"

The smooth muscle cell in culture

Abstract: The current state of knowledge of both vascular and visceral smooth muscle in cell and tissue culture and the variety of preparations used for different experimental purposes are described. Organ culture of smooth muscle tissues is referred to only periodically.

Control of acetylcholine receptors in skeletal muscle

Abstract: An ACh receptor is the molecular entity that, in its native habitat, possesses the binding sites for ACh and all the other components required to generate the ion channels mediating the ACh response. Narrower definitions of an ACh receptor (as the binding site for ACh or the polypeptide chain that is folded to form the binding site) could lead to semantic arguments about receptor structure. Experimentally, ACh receptors are defined by their total function (when electrophysiological tests are used) or by ligand binding. There is no evidence that the ligand-binding portions of ACh receptors ever exist in vivo without the associated channel-forming mechanism and vice versa. Most data are consistent with the idea that detergent-solubilized glycoproteins retaining the ACh binding sites of the receptor also include the channel-forming components, although it appears that the mechanism is prone to denaturation or proteolytic damage. Studies of receptor-rich membranes and of solubilized receptor glycoprotein have not yet yielded a totally satisfactory image of receptor structure. Most evidence favors an ACh receptor composed of three or four different types of glycosylated polypeptide chains organized into a unit of aggregate molecular weight about 300,000--400,000 daltons. Plasma membranes are dynamic structures in two different ways. First, their constituent molecules are in rapid thermal motion and, when these molecules are not tethered to extramembranous structures or mired in large aggregates, they fairly rapidly change their position in the plane of the lipid bilayer. Second, all membrane components are continually being synthesized and degraded. Acetylcholine receptors participate in both aspects of this dynamism. In this review it is proposed that the number and the distribution of ACh receptors in skeletal muscle are controlled by modulation of receptor metabolism and modulation of associations between receptor molecules or between receptors and other, as yet unidentified, elements in neuromuscular junctions and at extrajunctional sites where receptors are clustered. The arrangements of receptors in skeletal muscle and the total number of receptors in skeletal muscle may be regulated by separate mechanisms. Clusters of ACh receptors apparently can form spontaneously in extrajunctional areas of denervated muscles and in tissue-cultured embryonic muscle. Such clusters may be positionally stable and the receptor molecules in them may be highly restricted in mobility. Nevertheless, these receptors have average lifetimes on the order of 20 h, just like the nonclustered, mobile extrajunctional receptors. Receptor clusters also form at sites of innervation. In the chick embryo the junctional receptor molecules remain short-lived. The metabolism of ACh receptors is highly regulated. The biosynthesis of receptors commences during myogenesis at about the time myogenic cells become competent to fuse. Later, biosynthesis is dramatically repressed by muscle activity and possibly by other factors...

Endocrine control of parturition

Abstract: A sizable problem in our understanding of the control of parturition has been a desire by different investigators to explain the whole mechanism in terms of their current theory. We have been offered explanations in terms of factors such as withdrawal of the systemic progesterone block, the local progesterone block, the volume:progesterone ratio, the progesterone:estrogen ratio, the oxytocin effect, the progesterone:oxytocin effect, the fetal role, and the prostaglandin role. With the coming of age of Endocrinology and the ability to reduce hormone assays to a routine laboratory service, we have at last begun to understand that many, if not all, rather than any one of these individual explanations may be implicated in the control of parturition. We now recognize that in late pregnancy a train of events is initiated that ultimately results in the delivery of the fetus. However, we still do not know exactly how and where that train starts, or exactly how it exerts its ultimate action on the myometrial cell. It is a major objective of this chapter to try to bring together some of the abovementioned theories, and particularly to show that, for example, the role of the fetus in the initiation of parturition and the concept of progesterone withdrawal may be part of the same mechanism. It would be folly to say that at the present time either or both of these concepts explain parturition in all species, but by examining a number of different species we hope to illustrate as many of the discrepancies as similarities.

Functional adaptation to reduction in renal mass.

Abstract: As the population of nephrons diminishes, while the dietary intake and/or endogenous production of water and solutes is unchanged, there is a proportional increase in the excretion of water and solute by individual residual nephrons. This adaptive change, which preserves zero net balance in the early phase of renal insufficiency, involves a reduction in the fractional reabsorption of substances derived from the initial glomerular ultrafiltrate and an increase in the rate of secretion of solutes that are extracted by tubular epithelial cells from peritubular blood. These compensatory changes are adequate to maintain electrolyte and water homeostasis until severe renal failure ensures (GFR less than 20% of normal). After a moderate reduction in nephron population there is no evidence that the factors that modulate ion transport are qualitatively different from those that regulate renal function in the intact subject, when the excretory load of solute is varied by changes in intake or endogenous production. In severe renal insufficiency, however, it seems likely that several factors, not present in the subject with intact renal function, also play an important role in modifying the excretion of water and electrolytes. For example, an osmotic diuresis in severe renal failure apparently decreases the tubular reabsorption of sodium and divalent cations and that of water. Moreover, elaboration of a partially identified "natriuretic" substance may participate in the regulation of electrolyte excretion in severe renal insufficiency. The appearance of these factors in severe renal insufficiency probably complements mechanisms that normally regulate the transfer of water and ions across tubular epithelium, since even after a marked reduction in GFR the urinary excretion of solutes and water changes proportionally with intake, although within narrower limits than exist in normal subjects. Studies in experimental animals and in man with acquired renal disease demonstrate the important role of other factors in compensatory adaptation, in addition to changes in tubular transport. The marked increases in glomerular filtration rate and nephron blood flow, which occur at least in some conditions, increase the absolute amount of water and solute delivered to the various nephron segments in ultrafiltrate and peritubular blood. Moreover, the expansion of extracellular fluid in severe renal failure inhibits tubular reabsorption of filtered water and solute in the same qualitative way that has been demonstrated in subjects with intact renal function. Quantitatively the response to acute volume expansion is exaggerated compared with control. Concomitant changes in renal hypertrophy and hyperplasia probably play an important role in functional adaptation. The apparent marked capacity for compensatory growth in all nephron segments and even in portions of tubular segments in parenchymal renal disease increases the area for transport by tubular epithelia in residual nephrons, as the overall number of nephrons diminishes...

Assessment of protein turnover by use of radioisotopic tracers

Abstract: The principles of chemical kinetics were applied to turnover studies soon after tracers had been introduced into biological experiments, and several reviews on this subject are available. However, rigorous precursor-product analysis of protein turnover was seldom attempted in the past, mostly because it was assumed that the radioactive precursors of proteins are rapidly eliminated from the organisms. The estimate of protein half-life therefore was based on measurements of decay of the protein radioactivity only. Although such experiments clearly confirmed the dynamic state of protein molecules, it was later recognized that this approach leads to a gross overestimate of protein half-lives because the tracer amino acids are not eliminated as fast as had been thought. The omission of precursor specific radioactivity in calculations of turnover rates thus is not justified. Consequently, any meaningful measure of protein turnover requires determination of the specific radioactivity of the amino acid, both in the protein molecule and in the precursor pool.

Neural control of heartbeat in the leech and in some other invertebrates

Abstract: The heartbeat of the leech Hirudo consists of the contractile rhythm of the circular muscles in the wall of a bilateral pair of celomic sinuses, the heart tubes, that run the length of the leech bo...