The properties of angiotensin II (AII) receptors and their intracellular signalling pathways were studied in the adrenal zone glomerulosa and other target tissues. The mechanisms leading to stimulation of steroidogenesis were analyzed in isolated glomerulosa cells from the rat and bovine adrenal cortex. Purification of photolabeled AII receptors of the bovine adrenal gland was pursued by detergent solubilization and fractionation by ion exchange, lectin-affinity, and immunoaffinity chromatography. Elevation of cytoplasmic calcium by AII depends upon mobilization of intracellular calcium stores by the products of ligand-stimulated phosphoinositide turnover, and also on calcium entry through voltage-sensitive channels. Microsomal receptors for inositol-1,4,5-trisphosphate (IP3), previously identified in adrenal microsomes, were also demonstrated in the anterior pituitary gland. The Ins-1,4,5-P3 formed from PIP2 breakdown during AII action was rapidly eliminated via two metabolic routes. In addition to breakdown via Ins-1,4-P2 and Ins- 4-P via the previously identified 4-monophosphate pathway, the calcium-mobilizing 1,4,5-trisphosphate isomer is rapidly converted to Ins-1,3,4,5-P4, which is then degraded to the inactive 1,3,4-trisphosphate isomer. The latter is metabolized by degradation to Ins-3,4-P2 and Ins-1,3-P2, and also undergoes a further cycle of phosphorylation to form a novel tetrakisphosphate isomer, recently identified as Ins-1,3,4,6-P4. These studies have further indicated the importance of the 4- monophosphate pathway in inositol polyphosphate catabolism, and have revealed new phosphorylation pathways and inositol metabolites with potential roles in intracellular signalling and AII action in the glomerulosa cell and other target tissues.
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