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The differentiation of the juxtaglomerular apparatus in fetuses and newborn mice was investigated by renin immunocytochemistry and electron microscopy. Three to four days before delivery and prior to other organs renin was found in the fetal kidney. At this early time immunoreactivity was preferentially located in cells of the media of interlobular arteries. In newborn mice the formation of new nephrons and maturation of their glomeruli was accompanied by a shift in renin localization from the interlobular arteries to the afferent arterioles. At the same time, kidney renin content and concentration increased rapidly. Synchronously with renin immunoreactivity, during the capillary loop stage of glomerular development, granulated epitheloid cells became visible in the afferent arteriole.

The hormone-sensitive adenylate cyclase is a multi-component system embedded in the lipid bilayer of the plasma membrane and serves as a signal transduction system for various membrane receptors. The complete system consists of various receptor molecules, which sensitize the external ligands, the effector enzyme adenylate cyclase, which catalyzes the formation of cyclic AMP from ATP, and two guanine nucleotide-binding regulatory proteins (N or G proteins), which transduce the signals from the receptors to the adenylate cyclase. Depending on the receptor type activated by a ligand, stimulatory or inhibitory, either the stimulatory or the inhibitory N protein is activated and induces stimulation or inhibition of adenylate cyclase with subsequent increase or decrease in cellular cyclic AMP levels. In this paper, the mechanisms of this hormonal signal transduction system and its regulation will briefly reviewed, with some emphasis on the cardiac system.

Agonist binding to various hormone receptors mediating adenylate cyclase inhibition is decreased by sodium ions. We studied the influence of Na+ on agonist and antagonist binding to beta-adrenoceptors in membrane preparations of guinea pig lung, S49 lymphoma wild-type cells (WT) and their Ns-deficient cyc- variants by measuring binding of the antagonist, [125I]iodocyanopindolol [( 125I]CYP). At 37 degrees C, sodium decreased the receptor affinity for the agonist, isoproterenol, in all three membrane preparations. In lung and WT membranes, Na+ steepened the shallow agonist competition curves in a manner similar to and synergistic with guanine nucleotides. When binding was performed at 4 degrees C, sodium regulation but not guanine nucleotide regulation of agonist binding was preserved. At the low temperature, [125I]CYP affinity was reduced, and sodium increased [125I]CYP binding in both Ns-containing and Ns-deficient membranes by increasing the antagonist affinity without significant change in total receptor number. Compared to Na+, Li+ and K+ were much less potent and efficient in decreasing agonist and increasing antagonist binding. Na+ and Mg2+ had opposite effects on agonist binding in the Ns-containing lung and WT membranes but not in the Ns-deficient cyc- membranes. The data indicate that sodium not only regulates binding of inhibitory hormone receptors but also agonist and antagonist binding to the adenylate cyclase stimulatory beta-adrenoceptor. The finding that sodium regulation of beta-adrenoceptor binding is also observed in the Ns (alpha s)-deficient cyc- membranes, furthermore, indicates that the target of sodium is not the alpha-subunit of Ns but possibly a component common to both types of receptor systems regulating adenylate cyclase activity.

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