STEROIDOGENESIS IN ISOLATED RAT ADRENAL GLOMERULOSA CELLS: RESPONSE TO PHYSIOLOGICAL CONCENTRATIONS OF ANGIOTENSIN II AND EFFECTS OF POTASSIUM, SEROTONIN AND [Sar1,Ala8]-ANGIOTENSIN II

Abstract

Zona glomerulosa cell suspensions with less than 5 % fasciculata-reticularis cell contamination were prepared by collagenase digestion of normal rat adrenal capsular tissue. The corticosterone and aldosterone content of such cell suspensions under various conditions were measured simultaneously. Increases in steroid production were observed with physiological concentrations of angiotensin 11 (2 \ m=x\10\m=-\11 mol/l), with sigmoid log dose-response curves for both corticosterone and aldosterone production (ED50:4 \m=x\10\m=-\10and 8 \m=x\10\m=-\10mol angiotensin II/l respectively). The response to angiotensin II could be abolished by [Sar1, Ala8]-angiotensin II ; 50 % inhibition was produced by an equimolar concentration of this antagonist. Extracellular potassium ion concentration was shown to affect steroid output dramatically, confirming previous observations and underlining its importance as a physiological regulator of aldosterone secretion. The characteristics of the effect of serotonin, a potent stimulator of steroidogenesis in this system, were also observed. Differences in the maximal responses to angiotensin II and serotonin could not be explained by degradation and probably reflect their different modes of action.Zona fasciculata-reticularis cell suspensions were prepared in a similar fashion from decapsulated adrenal glands, and showed no increase in steroid production with those concentrations of angiotensin II (2 \m=x\10\m=-\11to 2 \m=x\10\m=-\7 mol/l) that stimulated glomerulosa cells. However, angiotensin II amide did increase corticosterone production in isolated fasciculata-reticularis cells at concentrations greater than 2 \m=x\ 10\ m=-\ 5mol / l , as reported by others, whereas angiotensin free acid did not.It is concluded that this sensitive rat glomerulosa cell suspension will be useful for studying the modes of action of angiotensin II and other stimulators of aldosterone biosynthesis.

5-HT, alpha-adrenoceptors, and blood pressure. Effects of ketanserin in essential hypertension and autonomic insufficiency.

“…From studies with isolated rat glomerulosa cells it is known that 5-HT has direct aldosterone-stimulating properties. 23 Suppression of aldosterone was found in patients with idiopathic aldosteronism after administration of the antiserotonergic agent cyproheptadine. 24 The divergent responses of plasma renin and aldosterone after ketanserin in our patients suggest a suppressive effect of 5-HT blockade on aldosterone secretion but further studies are needed to clarify this point.…”

“…2 These binding sites probably differ 7 from the D-and M-types of 5-HT-receptors postulated by Gaddum and Picarelli. 23 The close connections between the central serotonergic neuronal system and the pathways of catecholaminergic neurons suggest a role for 5-HT in cardiovascular control, but both pharmacological and surgical 26 From animal studies, ketanserin appears to be more potent as a serotonin antagonist in the periphery than in the central nervous system. 6 The peripheral effects of 5-HT are notoriously variable.…”

Characterization of angiotensin receptors on bovine adrenal fasciculata cells.

“…High doses of All amide (hypertensin) also increase steroidogenesis in rat fasciculata-reticularis cells but this effect has been attributed to a corticotropin (ACTH)-like impurity (7). Therefore, before considering any effect on steroidogenesis to be of physiological significance, it is important to ascertain that pure angiotensins, possibly of different sources, have such an effect at low concentration.…”

“…Therefore, before considering any effect on steroidogenesis to be of physiological significance, it is important to ascertain that pure angiotensins, possibly of different sources, have such an effect at low concentration. We previously reported (8) that, in the zona fasciculata from bovine adrenals, not only All (9) but also its precursors, the decapeptide angiotensin I (Al) and AI nonapeptide [2][3][4][5][6][7][8][9][10] (des-Asp'-AI), possessed intrinsic activity without being converted to All and angiotensin heptapeptide 2-8, desAsp'-AII (AIII), respectively. AIII was as potent as All in stimulating steroid biosynthesis in the zona fasciculata.…”

Radioreceptor assays: plasma membrane receptors and assays for polypeptide and glycoprotein hormones

“…Subcellular particles (20,000 g) from bovine adrenal cortex have also been used in a radioreceptor assay for angiotensin II and its analogues (Saltman, Baukal, Waters, Bumpus & Catt, 1975 (Douglas, Saltman, Fredlund, Kondo & Catt, 1976;Bing & Schulster, 1976 (Grant & Vale, 1975), parathyroid hormone (Sutcliffe, Martin, Eisman & Pilczyk, 1973), somatomedin (Hall, Takano, Fryklund & Sievertsson, 1975) and thyroid-stimulating hormone (Amir, Carraway, Kohn & Winand, 1973 ;Verrier, Fayet & Lissitzky, 1974).…”