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Dopamine in rat adrenal glomerulosa
Life Sciences, Vol. 40, pp. 811-816 Printed in the U.S.A.
Pergamon Journal
DOPAMINE IN RAT ADRENAL GLOMERULOSA
J. Howard Pratt, Deborah A. Turner, Ronald R. Bowsher and David P. Henry
Richard L. Roudebush Veterans Administration Medical Center Lilly Laboratory for Clinical Research and Indiana University School of Medicine, Indianapolis, Indiana 46202 (Received in final form November 19, 1986) Summ~ey
There is increasing evidence that dopamine (DA) inhibits aldosterone production, but the source of DA for this dopamlnergic influence is not known. In the present study we examined the adrenal's zona glomerulosa for the presence of DA. Rats maintained on an intake of regular food were killed by decapitation and the adrenal capsule (containing zona glomerulosa) and the remainder of the gland (containing both cortex and medulla) were examined for their content of DA and also for norepinephrine (NE) and epinephrine (E). DA was found in adrenal glomerulosa in substantial quantity, 1.92 + 0.17 (SEM) ng/mg wet weight, representing an approximate concentration of DA of 1-100 ~ M. DA in adrenal capsule represented 12.2% of the total adrenal content of DA. NE and E were also present in glomerulosa, 3.46 + 0.32 and 18.7 + 2.1 ng/mg respectively, but, unlike DA, about 9~-% of the total a-drenal content of NE and E was contained in adrenal medulla. The NE/E ratio in capsule and medulla were similar, although slightly higher in adrenal medulla, suggesting that the medulla is the source of the NE and E found in glomerulosa. On the other hand, the DA/E ratio was several-fold higher in glomerulosa than medulla - suggesting that glomerulosa DA was derived at least partially from a source other than adrenal medulla. We also found that short-term culturing of the adrenal reduced DA levels to I/3 that observed in fresh tissue. This could explain in part why cultured glomerulosa has been shown to be more responsive to administered stimuli. In summary, the findings indicate a significant concentration of DA in adrenal glomerulosa, and suggest that the effects of DA on aldosterone production are mediated locally within the adrenal.
An extensive body of experimental data indicates that dopamine (DA) inhibits aldosterone secretlon. This dopaminergie effect on aldosterone production was convincingly demonstrated when metoclopramide, a DA antagonist, was shown to stimulate aldosterone secretion in humans (1,2), a response that could be reversed by DA administration (3,4). This effect of metoclopramlde was observed subsequently in several animal species as well (5-9). McKenna and co-workers (10,11) and Racz et al (12) showed that DA Copyright
0024-3205 $3.00 + .00 (c) 1987 Pergamon Journals Ltd.
812
Adrenal Dopamine
Vol. 40, No. 9, 1987
(~ 10 ~ M) reduces the aldosterone stimulatory response to angiotensin II in vitro, thus providing evidence for a direct adrenal effect of DA. In clinical studies, stimulation of aldosterone production by metoclopramide occurs in the absence of angiotensin II and in the absence of anterior pituitary function (13), again suggesting a direct effect of metoclopramide on the adrenal as opposed to an indirect action mediated through angiotensin II or through secretion of a pituitary hormone.
The demonstration of DA in the zona glomerulosa would provide more substantive evidence that DA contributes to the regulation of aldosterone production, and, further, that DA acts directly at the level of the adrenal. Studies by McCarty et al (14) and Kvetnansky et al (15) in the rat adrenal and by Racz et al (12) in the bovine adrenal showed that the adrenal cortex contains DA. However, there have been no measurements of DA restricted only to the glomerulosa portion of the cortex, the site where aldosterone is synthesized. In the present study DA was assayed in rat adrenal capsule where cortical cells adhering to the undersurface of the capsule are made up almost exclusively of zona glomerulosa.
Also in the present study, we examined the question of whether DA in the glomerulosa might be derived from DA stores in the adrenal medulla. In addition, the effect of short-term culture of adrenal capsule on the tissue concentrations of DA was studied.
Materials and Methods
Female Sprague-Dawley rats weighing 200-225 gm and maintained on an ad libitum intake of Purina laboratory chow were used for study. After rats were killed by decapitation, the adrenals were removed and hemisected, and the capsule carefully separated from the rest of the gland. Capsules were then thoroughly rinsed in Krebs Ringer bicarbonate buffer. The adrenal capsule, containing zona glomerulosa, and the remainder of the gland, containing medulla as well as zonae fasiculata and reticularis, were kept at 0°C while their wet weight was determined. Tissues were then stored frozen at -20°C until assayed for catecholamine content. The experimental protocol was carried out on two different occasions with data from both experiments pooled for analysis.
A separate set of tissue preparations consisted of placing freshly obtained capsule in culture for 24 hr prior to assaying for DA content. The details of the culturing procedure used have been described previously (16).
NE, E, and DA were quantified using a catechol-O-methlytransferase (COMT) and TLC based assay which was a modification of a previously published procedure (17). The COMT used in this procedure is highly purified and devoid of aromatic amino acid decarboxylase activity, and therefore no contamination of DA levels is induced by I-DOPA. The sensitivity of the procedure is 1.5, 1.0 and 0.5 pg for NE, E, and DA respectively. The within assay C.V. is 10.0%. Where appropriate the data were analyzed by the non-paired t-test.
Vol. 40, No. 9, 1987
Adrenal Dopamine
813
Results
Shown in Table I are the concentrations of NE, E and DA in adrenal capsule and non-capsular adrenal tissue (where catecholamine content is essentially that of adrenal medulla). Although adrenal medulla contained considerably higher concentrations of catecholamlnes, their concentrations in capsule were substantial. From these data we estimate that the molar concentration of NE, E and DA in adrenal glomerulosa is in the range of 1-100 ~ M, assuming the capsule consists primarily of cortical tissue that is both homogeneous and aqueous.
TABLE I
The Concentrations of .Nore~iqephrine (.NE), Epinephrine (E)_, and Dopamlne (DA) in Capsular _~nd Non-Capsular (Ad.re.nalMedulla) Tissues.
(n) A ~ e n a l capsule
NE nglmg (14) 3.46 + 0.32*
18.7 + 2.1
DA nglmg (14) 1.92 + G.17
Ad~mmal medulla
(16) 129 ± 11.6
(10) 618 ~ 103
(16) 13.8 ~ 1.47
*
= Mean
÷
E nglmg
(14)
SEM.
In Figure }, the NE/E and DA/E ratios in capsule and medulla are eampared. The NE/E fraction was quite similar in capsule and medulla, although there was a slight but significantly higher fraction in the medulla. In contrast, the DA/E ratio was considerably greater in capsule than in medulla (p < .001). These findings indicate that there is a relative preponderance of DA in the zone glomerulosa compared to the adrenal medulla.
The relative increase of DA in zona glomerulosa is also evident when the amounts of the different catecholamlnes in adrenal capsule are compared to their respective amounts in whole gland (Figure 2). The percentages of NE and E contained in adrenal capsule were 2.6 and 2.9% respectively, whereas 12.2% of the adrenal content of DA was found in adrenal capsule.
Cultured adrenal capsule contained 0.6 + 0.2 ng/mg DA (n=6). Thus, short-term culture reduced the concentration of DA to about I/3 that of fresh tissue.
Discussion
In the present study DA was found in zona glomerulosa in amounts that were shown by McKenna et al (10,11) to inhibit angiotensin II stimulated aldosterone production. Although others have shown DA in adrenal cortex (12,14,15), this is the first demonstration of its existence specificaly in
814
Adrenal Dopamine
Vol. 40, No. 9, 1987
zona glomerulosa - the only area of the adrenal regulate steroldogenesis.
where DA has been
shown
to
We can only speculate on the source of zona glomerulosa DA. Plasma levels of free DA appear to be too low to account for the tissue concentrations observed unless DA is sequestered and concentrated in the glomerulosa (12,18). Circulating conjugates of DA could also be taken up by cortical tissue and deconjugated to provide DA. However, the blood level of the major conjugate, the sulfoconjugate of DA, appears to be low (12), much like circulating DA, thus making this too an unlikely source of DA.
NE and E in glomerulosa appeared to arise from the adrenal medulla since the ratios of their respective concentrations were quite similar in glomerulosa and medulla. On the other hand the DA/E ratio was greater in glomerulosa than medulla suggesting that DA arose from a source other than adrenal medulla. Alternatively, DA might stem from a medullary source with its transport to the glomerulosa regulated differently from that of NE and E. Gallo-Payet and Pothier (11) found anatomic evidence for how catecholamlnes synthesized in the medulla might reach the glomerulosa. They have described columns of medullary cells extending out through the cortex and terminating in the glomerulosa. Conceivably all of the NE and E, and some of the DA, in the glomerulosa was transported from the medulla through such columns; also conceivably these columns of medullary cells could contain elements that preferentially synthesize DA. Other considerations include that the adrenal glomerulosa is innervated by dopaminergic neurons as opposed to typical adrenerglc peripheral nerves. Evidence against a neuronal source of DA (as well as an adrenal medullary source) is that alpha-methyl-para- tyrosine, an inhibitor of catecholamine synthesis within neural tissue, does not reduce levels of DA in the demedullated adrenal (14).
A potential non-neuronal, non-medullary source of DA is the decarboxylation by adrenal tissue of DOPA to DA by the enzyme amino acid decarboxylase. DOPA circulates in blood at much higher concentrations than DA (20), and amino acid decarboxylase activity has been identified in many tissues (21). However, this enzyme, to our knowledge, has not been looked for in adrenal glomerulosa, and thus the potential for such a mechanism remains unknown.
DA within the adrenal may convey a tonic inhibitory influence on aldosterone production as was suggested by Carey et al (2,3). In the present study we were able with short-term culture to deplete the glomerulosa of DA to levels that were I/3 that of fresh tissue. DeLean et al (22) have shown that bovine glomerulosa cells maintained in culture for I-2 days were more responsive to administered stimuli, even though basal aldosterone production was much less. We have made similar observations in rat adrenal capsule (unpublished observations). Conceivably this advantage of cultured tissue in terms of responsiveness to stimuli is in part a result of the lower levels of DA in these tissue preparations. The observations on the effects of short-term culture may be worthy of consideration in the preparation of the adrenal for in vitro studies of aldosterone production.
that
In conclusion, DA is can affect aldosterone
present in production.
zona glomerulosa in concentrations These findings further support a
Vol. 40, No. 9, 1987
Adrenal Dopamine
0,3-
815
0.3"
p
0.2-
j///Z
I
0.2-
T
I I I I I [ 1 [ I
o,I-
p
f
UJ
/ / I / I I I / / 1 1 /
0.1-
////
lY/,~ / I I I I I I I
IIiii
capsule
D
medulla
capaule
medulla.
Figure I The NE/E and DA/E ratios in adrenal capsule and in adrenal medulla (n = 14 for each group).
15-
I0-
2///. ¢///~
////.,
2"//.6, r / f / #
/III# ~I/i#
5-
# / i / ~
NE
I11 E
r i l l # r i l l # I I l l ~ e l / I / I I ] ] ~
DA
Figure 2 The percentage of adrenal catecholamlnes in the zona glomerulosa.
816
Adrenal Dopamine
role for DA to regulate production of aldosterone, to be mediated within the adrenal itself.
Vol. 40, No. 9, 1987
a role that would appear
Acknowledgements
We are grateful to Ostella Honeycutt for preparation of the manuscript. This work was supported by the Veterans Administration.
References
I. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22.
G. NORBIATO, M. BEVILACQUA, U. RAGGI, P. MICOSSI, and C. MORONI, J. Clin. Endocrinol. Metab. 45, 1313-1316 (1977) R.M. CAREY, M.O. THORNER, E.M. ORTT, J. Clin. Invest. 63, 727-735 (1979) R.M. CAREY, M.O. THORNER, E.M. ORTT, J. Clin. Invest. 66, 10-18 (1980) R.H. NOTH, R.W. McCALLUM, C. CONTINO, J. HAVELICK, J. Clin. Endocrinol. Metab. 51, 64-69 (1980) J.R. SOWERS, M.L. TUCK, M.S. GOLUB, E.G. SOLLARS, Endocrinology 107, 937-941 (1980) J.G. McDOUGALL, B.A. SCOGGINS, A. BUTKUS, J.P. COGHLAN, D.A. DENTON, D°T. FEI, K.J. HARDY, R.D. WRIGHT, J. Endocrinol. 91, 271-280 (1981) J°R. SOWERS, B. SHARP, E.R. LEVIN, M.S. GOLUB, P. EGGENA, Life Sci. 2_99, 2171-2175 (1981) M.T. ZANELLA, E.L. BRAVO, Endocrinology 111, 1620-1625 (1982) T°A. WILSON, D.L. KAISER, M.J. PEACH, E.M° WRIGHT, R.M. CAREY, Endocrinology 113, 887-892 (1983) T.J. McKENNA, D.P. ISLAND, W.E. NICHOLSON, G.W. LIDDLE, J. Clin. Invest. 64, 287-291 (1979) S.J. SEQUIRA, T.J. McKENNA, Endocrinology 117, 1947-1952 (1985) K. RACZ, N.T. BUU, O. KUCHEL, A. De LEAN, Am. J. Physiol. 247, E431-E435 (1984) J.H. PRATT, A. GANGULY, C.A. PARKINSON, M.H. WEINBERGER, Metabolism 30, 129-134 (1981) R. McCARTY, R.F. KIRBY, R.M. CAREY, Am. J. Physiol. 247, ET09-E713 (1984) R. KVETNANSKY, V.K. WEISE, N.B. THOA, I. KOPIN, J. Pharmacol. Exp. Ther. 209, 287-291 (1979) J.H. PRATT, D.A. TURNER, J.A. McATEER, D.P. HENRY, Endocrinology 117, 1189-1194 (1985) K.R. BOREN, D.P. HENRY, E.E. SELKERT, M.H. WEINBERGER, Hypertension ~, 383 (1980) R. KVETNANSKY, C.L. SUN, C.R. LAKE, N.B. THOA, T. TORDA, I.J. KOPIN, Endocrinology 103, 1868-1874 (1978) N. GALLO-PAYET, P. POTHIER, (Submitted to publication) 1986 G.A. JOHNSON, C.A. BAKER, R.T. SMITH, Life Sci. 26, 1591-1598 (1980) M.K. RAHMAN, T. GAGATSU, T. KATO, Biochem. Pharmacol. 30, 645-650 (1981) A. DeLEAN, K. RACA, N. McNICOLL, M-L. DESROSIERS, Endocrinology 115, 485-492 (1984)
Pergamon Journal
DOPAMINE IN RAT ADRENAL GLOMERULOSA
J. Howard Pratt, Deborah A. Turner, Ronald R. Bowsher and David P. Henry
Richard L. Roudebush Veterans Administration Medical Center Lilly Laboratory for Clinical Research and Indiana University School of Medicine, Indianapolis, Indiana 46202 (Received in final form November 19, 1986) Summ~ey
There is increasing evidence that dopamine (DA) inhibits aldosterone production, but the source of DA for this dopamlnergic influence is not known. In the present study we examined the adrenal's zona glomerulosa for the presence of DA. Rats maintained on an intake of regular food were killed by decapitation and the adrenal capsule (containing zona glomerulosa) and the remainder of the gland (containing both cortex and medulla) were examined for their content of DA and also for norepinephrine (NE) and epinephrine (E). DA was found in adrenal glomerulosa in substantial quantity, 1.92 + 0.17 (SEM) ng/mg wet weight, representing an approximate concentration of DA of 1-100 ~ M. DA in adrenal capsule represented 12.2% of the total adrenal content of DA. NE and E were also present in glomerulosa, 3.46 + 0.32 and 18.7 + 2.1 ng/mg respectively, but, unlike DA, about 9~-% of the total a-drenal content of NE and E was contained in adrenal medulla. The NE/E ratio in capsule and medulla were similar, although slightly higher in adrenal medulla, suggesting that the medulla is the source of the NE and E found in glomerulosa. On the other hand, the DA/E ratio was several-fold higher in glomerulosa than medulla - suggesting that glomerulosa DA was derived at least partially from a source other than adrenal medulla. We also found that short-term culturing of the adrenal reduced DA levels to I/3 that observed in fresh tissue. This could explain in part why cultured glomerulosa has been shown to be more responsive to administered stimuli. In summary, the findings indicate a significant concentration of DA in adrenal glomerulosa, and suggest that the effects of DA on aldosterone production are mediated locally within the adrenal.
An extensive body of experimental data indicates that dopamine (DA) inhibits aldosterone secretlon. This dopaminergie effect on aldosterone production was convincingly demonstrated when metoclopramide, a DA antagonist, was shown to stimulate aldosterone secretion in humans (1,2), a response that could be reversed by DA administration (3,4). This effect of metoclopramlde was observed subsequently in several animal species as well (5-9). McKenna and co-workers (10,11) and Racz et al (12) showed that DA Copyright
0024-3205 $3.00 + .00 (c) 1987 Pergamon Journals Ltd.
812
Adrenal Dopamine
Vol. 40, No. 9, 1987
(~ 10 ~ M) reduces the aldosterone stimulatory response to angiotensin II in vitro, thus providing evidence for a direct adrenal effect of DA. In clinical studies, stimulation of aldosterone production by metoclopramide occurs in the absence of angiotensin II and in the absence of anterior pituitary function (13), again suggesting a direct effect of metoclopramide on the adrenal as opposed to an indirect action mediated through angiotensin II or through secretion of a pituitary hormone.
The demonstration of DA in the zona glomerulosa would provide more substantive evidence that DA contributes to the regulation of aldosterone production, and, further, that DA acts directly at the level of the adrenal. Studies by McCarty et al (14) and Kvetnansky et al (15) in the rat adrenal and by Racz et al (12) in the bovine adrenal showed that the adrenal cortex contains DA. However, there have been no measurements of DA restricted only to the glomerulosa portion of the cortex, the site where aldosterone is synthesized. In the present study DA was assayed in rat adrenal capsule where cortical cells adhering to the undersurface of the capsule are made up almost exclusively of zona glomerulosa.
Also in the present study, we examined the question of whether DA in the glomerulosa might be derived from DA stores in the adrenal medulla. In addition, the effect of short-term culture of adrenal capsule on the tissue concentrations of DA was studied.
Materials and Methods
Female Sprague-Dawley rats weighing 200-225 gm and maintained on an ad libitum intake of Purina laboratory chow were used for study. After rats were killed by decapitation, the adrenals were removed and hemisected, and the capsule carefully separated from the rest of the gland. Capsules were then thoroughly rinsed in Krebs Ringer bicarbonate buffer. The adrenal capsule, containing zona glomerulosa, and the remainder of the gland, containing medulla as well as zonae fasiculata and reticularis, were kept at 0°C while their wet weight was determined. Tissues were then stored frozen at -20°C until assayed for catecholamine content. The experimental protocol was carried out on two different occasions with data from both experiments pooled for analysis.
A separate set of tissue preparations consisted of placing freshly obtained capsule in culture for 24 hr prior to assaying for DA content. The details of the culturing procedure used have been described previously (16).
NE, E, and DA were quantified using a catechol-O-methlytransferase (COMT) and TLC based assay which was a modification of a previously published procedure (17). The COMT used in this procedure is highly purified and devoid of aromatic amino acid decarboxylase activity, and therefore no contamination of DA levels is induced by I-DOPA. The sensitivity of the procedure is 1.5, 1.0 and 0.5 pg for NE, E, and DA respectively. The within assay C.V. is 10.0%. Where appropriate the data were analyzed by the non-paired t-test.
Vol. 40, No. 9, 1987
Adrenal Dopamine
813
Results
Shown in Table I are the concentrations of NE, E and DA in adrenal capsule and non-capsular adrenal tissue (where catecholamine content is essentially that of adrenal medulla). Although adrenal medulla contained considerably higher concentrations of catecholamlnes, their concentrations in capsule were substantial. From these data we estimate that the molar concentration of NE, E and DA in adrenal glomerulosa is in the range of 1-100 ~ M, assuming the capsule consists primarily of cortical tissue that is both homogeneous and aqueous.
TABLE I
The Concentrations of .Nore~iqephrine (.NE), Epinephrine (E)_, and Dopamlne (DA) in Capsular _~nd Non-Capsular (Ad.re.nalMedulla) Tissues.
(n) A ~ e n a l capsule
NE nglmg (14) 3.46 + 0.32*
18.7 + 2.1
DA nglmg (14) 1.92 + G.17
Ad~mmal medulla
(16) 129 ± 11.6
(10) 618 ~ 103
(16) 13.8 ~ 1.47
*
= Mean
÷
E nglmg
(14)
SEM.
In Figure }, the NE/E and DA/E ratios in capsule and medulla are eampared. The NE/E fraction was quite similar in capsule and medulla, although there was a slight but significantly higher fraction in the medulla. In contrast, the DA/E ratio was considerably greater in capsule than in medulla (p < .001). These findings indicate that there is a relative preponderance of DA in the zone glomerulosa compared to the adrenal medulla.
The relative increase of DA in zona glomerulosa is also evident when the amounts of the different catecholamlnes in adrenal capsule are compared to their respective amounts in whole gland (Figure 2). The percentages of NE and E contained in adrenal capsule were 2.6 and 2.9% respectively, whereas 12.2% of the adrenal content of DA was found in adrenal capsule.
Cultured adrenal capsule contained 0.6 + 0.2 ng/mg DA (n=6). Thus, short-term culture reduced the concentration of DA to about I/3 that of fresh tissue.
Discussion
In the present study DA was found in zona glomerulosa in amounts that were shown by McKenna et al (10,11) to inhibit angiotensin II stimulated aldosterone production. Although others have shown DA in adrenal cortex (12,14,15), this is the first demonstration of its existence specificaly in
814
Adrenal Dopamine
Vol. 40, No. 9, 1987
zona glomerulosa - the only area of the adrenal regulate steroldogenesis.
where DA has been
shown
to
We can only speculate on the source of zona glomerulosa DA. Plasma levels of free DA appear to be too low to account for the tissue concentrations observed unless DA is sequestered and concentrated in the glomerulosa (12,18). Circulating conjugates of DA could also be taken up by cortical tissue and deconjugated to provide DA. However, the blood level of the major conjugate, the sulfoconjugate of DA, appears to be low (12), much like circulating DA, thus making this too an unlikely source of DA.
NE and E in glomerulosa appeared to arise from the adrenal medulla since the ratios of their respective concentrations were quite similar in glomerulosa and medulla. On the other hand the DA/E ratio was greater in glomerulosa than medulla suggesting that DA arose from a source other than adrenal medulla. Alternatively, DA might stem from a medullary source with its transport to the glomerulosa regulated differently from that of NE and E. Gallo-Payet and Pothier (11) found anatomic evidence for how catecholamlnes synthesized in the medulla might reach the glomerulosa. They have described columns of medullary cells extending out through the cortex and terminating in the glomerulosa. Conceivably all of the NE and E, and some of the DA, in the glomerulosa was transported from the medulla through such columns; also conceivably these columns of medullary cells could contain elements that preferentially synthesize DA. Other considerations include that the adrenal glomerulosa is innervated by dopaminergic neurons as opposed to typical adrenerglc peripheral nerves. Evidence against a neuronal source of DA (as well as an adrenal medullary source) is that alpha-methyl-para- tyrosine, an inhibitor of catecholamine synthesis within neural tissue, does not reduce levels of DA in the demedullated adrenal (14).
A potential non-neuronal, non-medullary source of DA is the decarboxylation by adrenal tissue of DOPA to DA by the enzyme amino acid decarboxylase. DOPA circulates in blood at much higher concentrations than DA (20), and amino acid decarboxylase activity has been identified in many tissues (21). However, this enzyme, to our knowledge, has not been looked for in adrenal glomerulosa, and thus the potential for such a mechanism remains unknown.
DA within the adrenal may convey a tonic inhibitory influence on aldosterone production as was suggested by Carey et al (2,3). In the present study we were able with short-term culture to deplete the glomerulosa of DA to levels that were I/3 that of fresh tissue. DeLean et al (22) have shown that bovine glomerulosa cells maintained in culture for I-2 days were more responsive to administered stimuli, even though basal aldosterone production was much less. We have made similar observations in rat adrenal capsule (unpublished observations). Conceivably this advantage of cultured tissue in terms of responsiveness to stimuli is in part a result of the lower levels of DA in these tissue preparations. The observations on the effects of short-term culture may be worthy of consideration in the preparation of the adrenal for in vitro studies of aldosterone production.
that
In conclusion, DA is can affect aldosterone
present in production.
zona glomerulosa in concentrations These findings further support a
Vol. 40, No. 9, 1987
Adrenal Dopamine
0,3-
815
0.3"
p
0.2-
j///Z
I
0.2-
T
I I I I I [ 1 [ I
o,I-
p
f
UJ
/ / I / I I I / / 1 1 /
0.1-
////
lY/,~ / I I I I I I I
IIiii
capsule
D
medulla
capaule
medulla.
Figure I The NE/E and DA/E ratios in adrenal capsule and in adrenal medulla (n = 14 for each group).
15-
I0-
2///. ¢///~
////.,
2"//.6, r / f / #
/III# ~I/i#
5-
# / i / ~
NE
I11 E
r i l l # r i l l # I I l l ~ e l / I / I I ] ] ~
DA
Figure 2 The percentage of adrenal catecholamlnes in the zona glomerulosa.
816
Adrenal Dopamine
role for DA to regulate production of aldosterone, to be mediated within the adrenal itself.
Vol. 40, No. 9, 1987
a role that would appear
Acknowledgements
We are grateful to Ostella Honeycutt for preparation of the manuscript. This work was supported by the Veterans Administration.
References
I. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22.
G. NORBIATO, M. BEVILACQUA, U. RAGGI, P. MICOSSI, and C. MORONI, J. Clin. Endocrinol. Metab. 45, 1313-1316 (1977) R.M. CAREY, M.O. THORNER, E.M. ORTT, J. Clin. Invest. 63, 727-735 (1979) R.M. CAREY, M.O. THORNER, E.M. ORTT, J. Clin. Invest. 66, 10-18 (1980) R.H. NOTH, R.W. McCALLUM, C. CONTINO, J. HAVELICK, J. Clin. Endocrinol. Metab. 51, 64-69 (1980) J.R. SOWERS, M.L. TUCK, M.S. GOLUB, E.G. SOLLARS, Endocrinology 107, 937-941 (1980) J.G. McDOUGALL, B.A. SCOGGINS, A. BUTKUS, J.P. COGHLAN, D.A. DENTON, D°T. FEI, K.J. HARDY, R.D. WRIGHT, J. Endocrinol. 91, 271-280 (1981) J°R. SOWERS, B. SHARP, E.R. LEVIN, M.S. GOLUB, P. EGGENA, Life Sci. 2_99, 2171-2175 (1981) M.T. ZANELLA, E.L. BRAVO, Endocrinology 111, 1620-1625 (1982) T°A. WILSON, D.L. KAISER, M.J. PEACH, E.M° WRIGHT, R.M. CAREY, Endocrinology 113, 887-892 (1983) T.J. McKENNA, D.P. ISLAND, W.E. NICHOLSON, G.W. LIDDLE, J. Clin. Invest. 64, 287-291 (1979) S.J. SEQUIRA, T.J. McKENNA, Endocrinology 117, 1947-1952 (1985) K. RACZ, N.T. BUU, O. KUCHEL, A. De LEAN, Am. J. Physiol. 247, E431-E435 (1984) J.H. PRATT, A. GANGULY, C.A. PARKINSON, M.H. WEINBERGER, Metabolism 30, 129-134 (1981) R. McCARTY, R.F. KIRBY, R.M. CAREY, Am. J. Physiol. 247, ET09-E713 (1984) R. KVETNANSKY, V.K. WEISE, N.B. THOA, I. KOPIN, J. Pharmacol. Exp. Ther. 209, 287-291 (1979) J.H. PRATT, D.A. TURNER, J.A. McATEER, D.P. HENRY, Endocrinology 117, 1189-1194 (1985) K.R. BOREN, D.P. HENRY, E.E. SELKERT, M.H. WEINBERGER, Hypertension ~, 383 (1980) R. KVETNANSKY, C.L. SUN, C.R. LAKE, N.B. THOA, T. TORDA, I.J. KOPIN, Endocrinology 103, 1868-1874 (1978) N. GALLO-PAYET, P. POTHIER, (Submitted to publication) 1986 G.A. JOHNSON, C.A. BAKER, R.T. SMITH, Life Sci. 26, 1591-1598 (1980) M.K. RAHMAN, T. GAGATSU, T. KATO, Biochem. Pharmacol. 30, 645-650 (1981) A. DeLEAN, K. RACA, N. McNICOLL, M-L. DESROSIERS, Endocrinology 115, 485-492 (1984)