International review of physiology最新文献

The absorptive functions of the gallbladder are responsible for concentrating the Na+ salts of bile acids during interprandial periods. This can be attributed entirely to its ability to absorb NaCl (and NaHCO3) and water in isotonic proportions, thus reducing the volume of hepatic bile by 80%--90%. The results of studies employing gallbladders of several species are consistent with the presence of neutral NaCl (and NaHCO3) absorption that is due to the presence of a coupled (one-for-one) NaCl entry process at the mucosal membrane. Active Na+ extrusion from cell to serosal solution appears to provide the energy for cellular Cl- accumulation, and thus for transepithelial Cl- transport. The mechanism of Cl- exit from the cell to serosal solution is uncertain andrequires further study. Rabbit gallbladder provided an ideal preparation for the characterization of NaCl cotransport and continues to be the tissue of choice for further study of this mechanism. Electrophysiological studies support the concept of nonconductive NaCl cotransport and also suggest that departures from the process of strictly neutral salt absorption may be related to the presence of additional (diffusional) pathways for Na+ and/or Cl- movement across the mucosal membrane so that the mechanistic constraint of neutral copuling between the absorptive movements of these ions is removed. Under these conditions, a significant serosa-positive transepithelial PD is observed and a fraction of Cl- absorption may be electrically coupled to that of Na+. Water is absorbed passively by virtue of osmotic coupling to electrolyte transport. A region of hypertonicity generated within the epithelium, at the level of the lateral intercellular space, provides the driving force for osmotic water flow. In view of the high osmotic water permeability of the gallbladder, the degree of hypertonicity required to account for the rate of water absorption is probably smaller than originally anticipated and is likely to be difficult to detect experimentally. Recent studies of the effects of humoral and pharmacological agents on electrolyte and water transport suggest that the rate of fluid absorption may be subject to physiological regulation. For example, secretin, which stimulates a HCO3--rich biliary secretion, also inhibits the reabsorption of this HCO3--rich fluid by the gallbladder, and in this manner may expedite the neutralization of the duodenal lumen. Inquires aimed at defining the physiological control of the absorptive functions of the gallbladder should provide an exciting avenue for future studies.

Follicular maturation and development is a complex process of interrelated intra- and extraovarian events that ultimately lead to ovulation of a mature oocyte and transformation of the ruptured follicle into a corpus luteum. The primordial follicle consists of an immature oocyte arrested in the dictyate stage of meiosis, surrounded by a single layer of relatively undifferentiated granulosa cells. The oocyte remains in the immature state because of many factors, one of which is the oocyte maturation inhibitor (OMI) secreted by granulosa cells. The oocyte subsequently increases in size, and as the antrum forms it becomes surrounded by cumulus cells. The cumulus cells may be intimately involved in the action of O,I to arrest the oocyte in the immature state within the follicle, as well as the resumption of meiosis during the LH surge. The compartments of the follicle that change most dramatically during follicular maturation are the cells lining the follicle--the granulosa and thecal cells. Under the influence of estrogen and FSH, the granulosa cells proliferate and also acquire FSH receptors. At this time, the thecal compartment differentiates and surrounds the granulosa cells, but remains separated from them by a basement membrane. Steroid secretion by the antral follicle involves the interplay of androgens, estrogens, and progestins. Both the granulosa and thecal cell compartments contribute to follicular fluid and serum levels of steroids; the interaction of both cell types may be necessary for estrogen and progesterone secretion in some species. As a consequence of the presence of an elevated number of FSH receptors, the granulosa cells of the small antral follicle are able to respond to FSH in many ways, including increased cyclic AMP accumulation, activation of the aromatase system, and induction of LH receptors, which permits the granulosa cells to later respond to LH. The mechanism by which thecal cells acquire their LH receptors is presently unknown. The granulosa cells of the follicle may indirectly control their own maturation and the number of follicles maturing through the secretion of follicular inhibin, which decreases the pituitary output of FSH. Even though the granulosa cells have acquired large numbers of LH receptors, they are prevented from luteinizing prematurely by factors in follicular fluid, including estrogen and a luteinizing inhibitor (LI). As serum LH levels increase during the preovulatory LH surge, a number of events occur: resumption of oocyte meiosis, transformation of the steroid enzyme complex from estrogen to progesterone secretion, follicular rupture, and formation of the corpus luteum. Granulosa cells form the bulk of the corpus luteum, which secretes elevated amounts of progesterone for a fixed time period depending on the species. Before ovulation the preovulatory follicle must be exposed to and respond to adequate LH and FSH levels in order for the eventual corpus luteum to secrete elevated amounts of

The methodology developed to assess the permeability of capillaries has been extended and applied to the study of the uptake of materials by the intact liver. The sinusoidal membrane has been found to be freely permeable to dissolved substances, so that the Disse spaces are functionally a simple extension of the sinusoidal plasma space. With this free access, a concentration bolus of material dissolved in plasma is found to be propagated in a delayed fashion, to behave as if it were flowing within this larger space. Within the space an exclusion phenomenon is found: the collagen and ground substance within it reduce the proportion of the space accessible to larger molecules in a graded fashion. Beyond the Disse spaces the first biological barrier for substances characteristically taken up by the liver is the cell membrane of the hepatic parenchymal cells. The uptake of materials, in general, therefore has the characteristics of a membrane carrier transport process. The phenomena distinctively associated with this process include saturation kinetics, competitive inhibition, and isotope countertransport. Beyond the membrane those substances sequestered by biochemical transformations or biliary secretion are handled by processes that also show saturation effects. The multiple indicator dilution technique has been adapted to the study of the uptake of materials at the liver cell surface. The process has been modeled and outflow profiles have been shown to consist of a throughput component (which has not entered the cells) and a returning component (which has entered the cells and returned to the plasma space to emerge at the outflow). When the process at the cell membrane is concentrative, the throughput component is emphasized by the relatively larger delay caused in the returning component by virtue of the concentratively enlarged cellular volume. When the process is nonconcentrative, the returning component emerges earlier, so that throughput and returning components are not longer directly apparent and must be separated out by carrying out model analysis of the data with a digital computer. The uptake of tracer rubidium was found to be a typically concentrative process, and that of tracer glucose a nonconcentrative process. When substrate undergoes intracellular sequestration, a new set of phenomena emerge. The sequestration reduces the magnitude of the returning component in a tracer experiment and, with this, produces a steady state gradient in lobular concentration, a profile decreasing in magnitude from the portal area to the adjacent terminal hepatic venules. The diminution in returning components has been observed both for galactose and for the group of compounds characteristically secreted in bile in high concentration. The lobular gradient for galactose has been demonstrated autoradiographically. It is evident that a powerful new set of tools has emerged...

The glutathione transferases are abundant multifunctional proteins of liver cytosol. In addition to their catalytic activity, they also bind as nonsubstrate ligands a variety of compounds that contain a hydrophobic nucleus. Included among these ligands are organic anions such as bilirubin. The abundance of these proteins and their avid binding of bilirubin and its conjugates have encouraged investigation into their potential role in hepatic transport and metabolism of organic anions. These studies suggest that the glutathione transferases perform a binding function within the cell analogous to that of albumin extracellularly. Although there is no evidence that these proteins are responsible for recognition and uptake of organic anions from the vascular space, they influence net uptake by binding these substances within the cell, reducing their efflux into plasma. The relationship of intracellular binding of bilirubin to the conjugation and excretory mechanisms is the subject of investigation at the present time.