PubMed Health⌕ Search

Biomedical subjects

A Albiston

Publications and source records attributed to A Albiston.

7 recordsLinked to original sources

Receptor activity modifying proteins.

Our understanding of G protein-coupled receptor (GPCR) function has recently expanded to encompass novel protein interactions that underlie both cell-surface receptor expression and the exhibited phenotype. The most notable examples are those involving receptor activity modifying proteins (RAMPs). RAMP association with the calcitonin (CT) receptor-like receptor (CRLR) traffics this receptor to the cell surface where individual RAMPs dictate the expression of unique phenotypes. A similar function has been ascribed to RAMP interaction with the CT receptor (CTR) gene product. This review examines our current state of knowledge of the mechanisms underlying RAMP function.

Amino Acid Sequence↗

Angiotensin II infusion to the midgestation ovine fetus: effects on the fetal kidney.

Renal and cardiovascular responses to an intravenous infusion of ANG II (1 microg/h) or saline for 3 days were examined in ovine fetuses at midgestation (75-85 days of gestation, term 150 days). ANG II caused an increase in fetal blood pressure (36 +/- 2 to 44 +/- 3 mmHg) and urine flow rate (8 +/- 2 to a maximum of 18 +/- 6 ml/h). Plasma renin concentrations decreased in ANG II-infused fetuses. Fetal fluids (amniotic and allantoic) did not differ in volume or composition between the groups when measured at postmortem. There was no difference in the expression levels of the mRNA for the angiotensin (AT(1) or AT(2)) receptors between the two groups when measured by an RNase protection assay. However, there was a significant decline in renin and AT(1) receptor gene expression when measured by a real-time polymerase chain reaction method. These results indicate that ANG II is diuretic and pressor when infused at midgestation. ANG II can feedback to decrease renin secretion by the fetal kidney, and this may occur by decreased renin gene expression.

Angiotensin II↗

Ontogeny and regulation of the AT1 and AT2 receptors in the ovine fetal adrenal gland.

The expression and regulation of the receptors for angiotensin II (both AT1 and AT2) were examined in the ovine fetal adrenal gland by RNase protection assay (RPA), in situ hybridisation histochemistry, immunohistochemistry and Western blotting. Both mRNA and protein for the AT1 receptor were present in the zona glomerulosa and zona fasciculata of the cortex, but not in the medulla, from as early as these zonas were distinguishable (60 days of gestation; term is 145-150 days), and even present in the steroidogenic cells of the unzoned gland at 40 days. The mRNA for the AT2 receptor was present in the same locations (but never in the medulla) from 40-130 days, and declined to extremely low levels after 140 days. The infusion of ang II, 1 microg/h, for 3 days, at mid-gestation (76 +/- 2 days) caused a significant decrease in mRNA for AT1 but no change in AT2 levels. Thus, the biologically active receptor (in terms of aldosterone stimulation) is present in the ovine fetal adrenal from very early in development, and can be down-regulated by mid-gestation.

Adrenal Glands↗

The renin-angiotensin system and the development of the kidney and adrenal in sheep.

1. The earliest form of the kidney, the pronephros, does not really occur in the ovine embryo; instead, a giant glomerulus forms at the anterior end of the mesonephros. 2. In the sheep, the mesonephros is present from 11-38% of total gestation (150 days) and produces a dilute urine, as well as expressing the genes for erythropoietin, renin, angiotensinogen, angiotensin-converting enzyme and the angiotensin II (AngII) receptors AT1 and AT2. 3. The ovine metanephros begins to develop at 18% of gestation and nephrogenesis is complete several weeks before birth. All components of the renin-angiotensin system (RAS) are expressed from at least 27% of gestation. 4. Both AT1 and AT2 receptors are expressed by the adrenocortical cells early in gestation but, at mid-gestation, exogenous AngII does not stimulate aldosterone secretion in vivo. 5. Preliminary results suggest that AngII has important roles in renal development in the ovine foetus but the role(s), if any, in adrenal development, remains to be investigated.

Adrenal Glands↗

Ontogeny of angiotensin II receptors, types 1 and 2, in ovine mesonephros and metanephros.

By RNAse protection assay, hybridization histochemistry, and in vitro autoradiography it was shown that both mRNA and protein for AT1 and AT2 receptors were present in ovine fetal meso- and metanephroi at 40 days of gestation (term approximately 150 days). AT1 mRNA was localized to presumptive mesangial cells of glomeruli at 40-, 75-, 131-gestational-day-old fetuses and two-day-old lambs, in addition to being widely present in interstitial cells of the cortex and medulla, once these zones formed (60 days). By two days after birth the medullary AT1 distribution was confined to the inner stripe of the outer medulla. AT2 mRNA was present in peripheral interstitial/tissue of the mesonephros, and interstitial tissue surrounding developing glomeruli, but not the outermost nephrogenic mesenchyme in the metanephros from 40 to approximately 131 days (the period of active nephrogenesis). In addition, AT2 mRNA was localized to epithelial cells of the macula densa in metanephroi (40 to 131 gestational days) during, but not after completion, of nephrogenesis. These studies suggest that angiotensin II (Ang II) could have differentiating effects, via AT1 receptors, from very early in development. The unique epithelial site of AT2 expression in the macula densa raises the possibility that Ang II may play a role in the invariant positioning of the macula densa at the pole of its glomerulus, via this receptor.

Aging↗

Rat follistatin: gonadal and extragonadal expression and evidence for alternative splicing.

Follistatin (FS) or FSH-suppressing protein is a polypeptide which exists in multiple forms and has inhibin-like activity. We investigated the distribution of tissues expressing FS mRNA. A segment of the rat FS mRNA corresponding to the last 157 nucleotides of exon 5 and the first 71 nucleotides of exon 6 was prepared by PCR and subcloned in plasmid GEM4Z (pGEM4Z) to produce a radiolabeled RNA probe. S1-Nuclease analysis of RNA extracted from rat tissues indicated alternative splicing of the rat FS gene and gonadal as well as extragonadal expression. In addition to the ovary and testis, the FS mRNA was detected in cerebral cortex, pituitary, adrenal, thymus, pancreas, gut, kidney, heart, uterus, skeletal muscle and lung. Treatment of female rats with combined Pregnant Mare Serum Gonadotropin (PMSG) and human Chorionic Gonadotropin (hCG) increased expression of FS mRNA in the ovary. Our results show that the mRNA for the precursor of the larger known form of FS (FS 344) is much more abundant than the mRNA for the smaller molecule (less than 5%) and that stimulation of FS transcription by PMSG and hCG in the ovary does not change this relationship.

Animals↗

Regulation and function of steroid production by mid gestation ovine fetal adrenal cortex in vivo.

By mid-gestation (75-85 days, term=150 days), the ovine fetal adrenal gland is zoned into cortex and medulla. The cortex has an outer layer of cells which have the morphological characteristics of zona glomerulosa cells, containing mitochondria with lamellar cristae. It has been reported that cultured adrenal cells from mid-gestation bovine and ovine fetuses can be stimulated to increase aldosterone production, ten fold, by angiotensin II, and that this can be maintained for at least 3 days. However, the situation in vivo is unknown. In the current report we show that in chronically cannulated ovine fetuses at mid-gestation, angiotensin II (1 microg/h) does not increase aldosterone either in the short term (3 hours) or long term (3 days). However, ACTH (450 ng/h) can increase plasma aldosterone in the short but not long term. ACTH at this dose produces progressive and large increases in cortisol production. Angiotensin II is pressor and produces a modest diuresis without stimulating cortisol.

Adrenal Cortex↗