Angiotensin II Increases Catecholamine Release from Bovine Adrenal Medulla but Does Not Enhance That Evoked by K+ Depolarization or by Carbachol

The effect of angiotensin II on catecholamine release from bovine adrenal medulla has been investigated. In retrogradely perfused, isolated bovine adrenal glands, angiotensin II increased basal efflux of catecholamines, but the presence of angiotensin II did not increase the release of catecholamines evoked either by bolus injections of the secretagogue carbachol or by depolarization with a perfusing solution containing a raised concentration of K+. In chromaffin cells maintained in primary tissue culture, angiotensin II increased 3H release from cells preloaded with [3H]-noradrenaline but did not enhance the release evoked by carbachol or by depolarization with K+. The increase in 3H release evoked by angiotensin II from chromaffin cells in tissue culture was inhibited by its analogue antagonist Sar1,Ala8-angiotensin II (saralasin) and was entirely dependent on the presence of Ca2+ in the experimental medium. These findings suggest that, in the chromaffin cells of the bovine adrenal medulla, angiotensin II acts on specific receptors to cause a calcium-dependent catecholamine release but triggers no additional response that acts synergistically with depolarizing or nicotinic stimuli to augment catecholamine release.     

Nature of the mutation in adult beta-galactosidase deficient patients.

Fibroblasts from three chronically affected, beta-galactosidase deficient adults were shown to synthesize nearly normal quantities of immunologically reactive catalytically deficient beta-galactosidase, indicating that they are CRM + structural mutants.     

ZnT3 mRNA levels are reduced in Alzheimer's disease post-mortem brain

Extensive genetic, biochemical, and histological evidence has implicated the amyloid-β peptide (Aβ) in Alzheimer's disease pathogenesis, and several mechanisms have been suggested, such as metal binding, reactive oxygen species production, and membrane pore formation. However, recent evidence argues for an additional role for signaling mediated by the amyloid precursor protein, APP, in part via the caspase cleavage of APP at aspartate 664. Here we review the effects and implications of this cleavage event, and propose a model of Alzheimer's disease that focuses on the critical nature of this cleavage and its downstream effects.     

Transport lattice models of heat transport in skin with spatially heterogeneous,temperature-dependent perfusion

Background  

Investigation of bioheat transfer problems requires the evaluation of temporal and spatial distributions of temperature. This class of problems has been traditionally addressed using the Pennes bioheat equation. Transport of heat by conduction, and by temperature-dependent, spatially heterogeneous blood perfusion is modeled here using a transport lattice approach.     

Analysis of insulin-receptor phosphorylation sites in intact cells by two-dimensional phosphopeptide mapping.

Insulin stimulates the autophosphorylation of the partially purified insulin receptor initially on tyrosine residues 1146, 1150 and 1151. This is followed by increased autophosphorylation of tyrosine residues 1316, 1322 and two further residues, possibly tyrosine residues 953 and 960 or 972 [Tavaré & Denton (1988) Biochem. J. 252, 607-615]. In the present paper we have used two cell lines transfected with insulin-receptor cDNA (CHO.T and NIH 3T3 HIR3.5 cells) to assess which tyrosine residues are phosphorylated on the insulin receptor within intact cells. We show that: (1) insulin causes a rapid increase in phosphorylation of tyrosine residues 1146, 1150 and 1151 in both cell types; tyrosine residues 1316 and 1322 are also phosphorylated, but apparently to a lesser extent in NIH 3T3 HIR3.5 cells; (2) the sites that may correspond to tyrosine residues 953 and 960 or 972 appear to be very poorly phosphorylated in both intact cell types; (3) insulin also promotes a substantial and rapid increase in the phosphorylation of serine and threonine residues on insulin receptors on CHO.T cells; this results in the appearance of two phosphopeptides not evident in the maps of the solubilized receptor preparations autophosphorylated in vitro.     

Synergistic enhancement of type I and III collagen production in cultured fibroblasts by transforming growth factor-β and ascorbate

Transforming growth factor-β (TGF-β) is a prototype of a family of polypeptides that regulates cellular growth and phenotypic differentiation [(1986) Science 233, 532-534; (1987) Cell 49, 437-438]. TGF-β injection induces angiogenesis and fibrosis locally [(1986) Proc. Natl. Acad. Sci. USA 83, 4167-4171; (1987) Science 237, 1333-1336] and stimulates the synthesis of extracellular matrix proteins, fibronectin, collagens, and proteoglycans in vitro in many cell types [(1986) J. Biol. Chem. 261, 4337-4345; (1987) Biochem J. 247, 597-604]. Ascorbate is also known to induce collagen synthesis and to promote wound healing [(1988) J. Invest. Dermatol. 90, 420-424; (1986) Coll. Rel. Res. 6, 455-466]. We report that in cultured human skin fibroblasts, ascorbate and TGF-β synergistically enhance the biosynthesis of type I and III collagens and their steady-state mRNAs. TGF-β alone has no enhancing effect on type III collagen synthesis. The cooperation between ascorbate and TGF-β may be of significance in wound healing and in disorders of fibrosis.