J. Steroid Biochem. Molec. Biol. Vol. 40, No. 1 3, pp. 437-439, 1991
0960-0760/91 $3.00 + 0.00 Copyright © 1991 Pergamon Press plc
Printed in Great Britain. All rights reserved
ON ALDOSTERONE OF THE ENDOTHELINS CELLS S E C R E T I O N BY R A T Z O N A G L O M E R U L O S A
EFFECT
IN VITRO J. P. HINSON,* S. KAPAS, R. TEJA a n d G. P. VINSON Department of Biochemistry, Faculty of Basic Medical Sciences, Queen Mary and Westfield College, Mile End Road, London El 4NS, England S u m m a r y - - E n d o t h e l i n s are t h o u g h t to be involved in the local regulation of b l o o d flow a n d tissue function. These experiments were carried out to investigate the possible role of endothelins in the control of aldosterone secretion by the rat adrenal. Suspensions of z o n a glomerulosa cells were p r e p a r e d by collagenase digestion o f capsular tissue, a n d i n c u b a t e d in the presence o f increasing c o n c e n t r a t i o n s of endothelin. A i d o s t e r o n e was m e a s u r e d by RIA. All three peptides caused a dose-dependent increase in the secretion rate o f aldosterone by zona glomerulosa cells. The m i n i m u m c o n c e n t r a t i o n of peptide required to give a significant response was 10-14mol/1 for endothelins 2 a n d 3 a n d 10-13mol/1 for endothelin 1. A t a c o n c e n t r a t i o n of l0 -7 mol/1 endothelin 2 elicited a 20-fold increase over basal aldosterone secretion, while b o t h endothelins 1 a n d 3 elicited a 30-fold increase ( P < 0.001 in all cases). These results show t h a t the endothelins are p o t e n t stimulators of aldosterone secretion, a n d suggest t h a t these peptides m a y have a role in the control o f zona glomerulosa function.
INTRODUCTION
RESULTS
The endothelins are a family of three recently identified vasoactive peptides which are structurally and pharmacologically distinct: endothelin 1 is made by endothelial cells; endothelin 3 is thought to be of neural origin; while the source of endothelin 2 is unknown (see Ref. [1] for a review). The endothelins have a wide range of biological properties [2], and receptors for these peptides have been identified in many tissues, including the adrenal gland [3]. The present studies are designed to investigate whether endothelins may have a role in the control of aldosterone secretion.
Aldosterone was stimulated in a dose-dependent manner by each of the peptides tested (Figs 1-3). The minimum concentration of each peptide required for significant stimulation of aldosterone secretion w a s 10 -13 mol/l for endothelin 1, and 10-la mol/1 for endothelins 2 and 3. 150
100
o
E
Q.
MATERIALS AND METHODS
C; "O
Collagenase-dispersed rat zona glomerulosa cells were prepared and incubated as described previously [4]. Endothelin 1, 2 and 3 were purchased from Bachem U.K. (Saffron Walden, Essex) and ACTH 1-24 (Synacthen) was obtained from Ciba-Geigy (Horsham, Sussex). Aldosterone was measured by RIA [5].
0960-0760/91 $3.00 + 0.00 Copyright © 1991 Pergamon Press plc
Printed in Great Britain. All rights reserved
ON ALDOSTERONE OF THE ENDOTHELINS CELLS S E C R E T I O N BY R A T Z O N A G L O M E R U L O S A
EFFECT
IN VITRO J. P. HINSON,* S. KAPAS, R. TEJA a n d G. P. VINSON Department of Biochemistry, Faculty of Basic Medical Sciences, Queen Mary and Westfield College, Mile End Road, London El 4NS, England S u m m a r y - - E n d o t h e l i n s are t h o u g h t to be involved in the local regulation of b l o o d flow a n d tissue function. These experiments were carried out to investigate the possible role of endothelins in the control of aldosterone secretion by the rat adrenal. Suspensions of z o n a glomerulosa cells were p r e p a r e d by collagenase digestion o f capsular tissue, a n d i n c u b a t e d in the presence o f increasing c o n c e n t r a t i o n s of endothelin. A i d o s t e r o n e was m e a s u r e d by RIA. All three peptides caused a dose-dependent increase in the secretion rate o f aldosterone by zona glomerulosa cells. The m i n i m u m c o n c e n t r a t i o n of peptide required to give a significant response was 10-14mol/1 for endothelins 2 a n d 3 a n d 10-13mol/1 for endothelin 1. A t a c o n c e n t r a t i o n of l0 -7 mol/1 endothelin 2 elicited a 20-fold increase over basal aldosterone secretion, while b o t h endothelins 1 a n d 3 elicited a 30-fold increase ( P < 0.001 in all cases). These results show t h a t the endothelins are p o t e n t stimulators of aldosterone secretion, a n d suggest t h a t these peptides m a y have a role in the control o f zona glomerulosa function.
INTRODUCTION
RESULTS
The endothelins are a family of three recently identified vasoactive peptides which are structurally and pharmacologically distinct: endothelin 1 is made by endothelial cells; endothelin 3 is thought to be of neural origin; while the source of endothelin 2 is unknown (see Ref. [1] for a review). The endothelins have a wide range of biological properties [2], and receptors for these peptides have been identified in many tissues, including the adrenal gland [3]. The present studies are designed to investigate whether endothelins may have a role in the control of aldosterone secretion.
Aldosterone was stimulated in a dose-dependent manner by each of the peptides tested (Figs 1-3). The minimum concentration of each peptide required for significant stimulation of aldosterone secretion w a s 10 -13 mol/l for endothelin 1, and 10-la mol/1 for endothelins 2 and 3. 150
100
o
E
Q.
MATERIALS AND METHODS
C; "O
Collagenase-dispersed rat zona glomerulosa cells were prepared and incubated as described previously [4]. Endothelin 1, 2 and 3 were purchased from Bachem U.K. (Saffron Walden, Essex) and ACTH 1-24 (Synacthen) was obtained from Ciba-Geigy (Horsham, Sussex). Aldosterone was measured by RIA [5].
