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Biomedical subjects

G Aguilera

Publications and source records attributed to G Aguilera.

At least 163 records · Page 9Linked to original sources
PubMed1982

Angiotensin II receptors and prolactin release in pituitary lactotrophs.

Logical properties of angiotensin II receptors in the rat adenohypophysis were analyzed in cultured rat pituitary cells incubated with angiotensin II and known stimuli of pituitary hormone secretion. PRL release during incubation for 3 h with 3 nM angiotensin II was consistently increased by 68 +/- 5%, comparable with that elicited by TRH (63.1 +/- 4%). The ED50 of 0.5 nM for PRL release by angiotensin II was significantly lower than that of TRH (2.9 nM) in the same cell cultures. The antagonist analog [Sar1,Ala8]angiotensin II prevented the angiotensin-induced rise in PRL production but not that evoked by TRH, whereas dopamine and SRIF inhibited basal, angiotensin, and TRH-stimulated PRL release. Angiotensin II also caused a small increase in ACTH release but had no effect on the release of LH, TSH, and GH. Angiotensin II binding and PRL release were measured in partially purified lactotrophs prepared by elutriation, by which the initial cell suspension was separated into seven fractions. Most of the lactotrophs were present in the two fractions eluted at flow rates of 15.7 and 19.8 ml/min, as indicated by their immunoreactive PRL content. The 2.5- to 3.2-fold enrichment of lactotrophs was accompanied by a 2- to 3.5-fold increase in angiotensin II receptor concentration, with no change in binding affinity (Ka = 3.5 x 10(9) M-1). In the same fractions, angiotensin II-induced PRL release was similarly increased by 1.6- to 3.5-fold above basal, compared with values of less than 1 in the initial cell suspension and other fractions. The preferential location of angiotensin II receptors in the lactotroph-containing fractions and the close correlation between angiotensin II binding sites and stimulation of PRL release indicate the functional importance of the pituitary angiotensin II receptor sites. These findings also suggest that angiotensin II could contribute to the physiological regulation of PRL secretion.

Angiotensin II↗
PubMed1982

Characterization of somatostatin receptors in the rat adrenal glomerulosa zone.

Specific receptors for somatostatin have been identified and characterized in the rat adrenal glomerulosa zone in vivo and in vitro by binding studies with [125I]iodo-Tyr-somatostatin. In adult rats, the injection of [125I]iodo-Tyr-somatostatin was followed by rapid uptake of the labeled peptide in several tissues. The highest uptake was in the adrenal capsule, with a tissue to blood ratio of 4.5, followed by kidney, anterior pituitary, and liver with tissue to blood ratios of 2.0, 1.8, and 1.4, respectively. In vitro binding studies with adrenal capsular particles were performed at 16 C in the presence of bacitracin and thimerosal to reduce tracer degradation. Under these conditions, binding of [125I]iodo-Tyr-somatostatin to capsular membrane-rich fractions reached a steady state within 30-40 min and remained at a plateau for 120 min. Dissociation of bound somatostatin from its adrenal receptors was also rapid, with an initial half-time of 5 min. Equilibrium binding of somatostatin to adrenal capsular particles was saturable and of high affinity, with an association constant (Ka) of 1.5 x 10(10) M-1. The receptor-binding activities of several somatostatin analogs were consistent with their potencies as inhibitors of angiotensin II-stimulated aldosterone production in adrenal capsular cells and with their known biological activities upon GH release. These findings demonstrate that high affinity receptors with structural and biological specificities for somatostatin are present in the adrenal glomerulosa zone. Such receptors serve as the regulatory sites through which somatostatin inhibits the action of angiotensin II upon aldosterone production in the adrenal glomerulosa cell.

Adrenal Glands↗
PubMed1981

Somatostatin modulates effects of angiotensin II in adrenal glomerulosa zone.

The octapeptide angiotensin II is a major regulator of the adrenal glomerulosa zone, acting both as an acute stimulus of aldosterone secretion and as a trophic hormone which increases steroidogenic enzymes and angiotensin II receptors in glomerulosa cells. Angiotensin II also mediates the adrenal effects of altered sodium balance, and is essential for the aldosterone response to sodium restriction. However, the adrenal effects of angiotensin II are attenuated during sodium loading, suggesting that other local or humoral factors modulate its actions on adrenal glomerulosa function. Somatostatin, the somatotropin release inhibiting factor of the hypothalamus, has been shown to inhibit the secretion and action of several pituitary and non-pituitary hormones. Because somatostatin has been found in several non-neural tissues, and seems to act as a local regulator of endocrine function, we have now examined the possibility that it may also modulate the effects of angiotensin II in the adrenal glomerulosa cell. Our studies have shown that low concentrations of somatostatin specificity inhibit the production of angiotensin II-stimulated aldosterone, and that this action is mediated by specific, high-affinity receptors for somatostatin in the zona glomerulosa.

Adrenal Glands↗
PubMed1981

Circulating angiotensin II and adrenal receptors after nephrectomy.

Mineralocorticoid secretion is predominantly controlled by the octapeptide angiotensin II, which exerts trophic actions on the adrenal glomerulosa and acute regulatory effects on aldosterone biosynthesis. The trophic actions include stimulation of angiotensin II receptors and enzymes of the aldosterone biosynthetic pathway, with corresponding enhancement of the aldosterone secretory capacity of the adrenal gland. The positive regulatory action of angiotensin II on its adrenal receptors occurs with elevations of the circulating peptide concentration within the physiological range and probably contributes to the increased sensitivity of the adrenal during sodium deficiency. In this action, angiotensin II differs from other hormones which decrease their target-cell receptors. However, the increase in adrenal angiotensin II receptors following nephrectomy has been interpreted as evidence for a tonic down-regulating effect of angiotensin II on its adrenal receptors. To clarify these conflicting views we evaluated the effects of nephrectomy on adrenal angiotensin II receptors in relation to blood angiotensin II and plasma electrolyte levels. We show here that hyperkalaemia contributes markedly to the post-nephrectomy increase in adrenal angiotensin II receptors, and that circulating angiotensin II levels persist for an unexpectedly long period after nephrectomy, presumably due to tissue generation of the octapeptide.

Adrenal Cortex↗
PubMed1981

Mechanisms of inhibition of aldosterone secretion by adrenocorticotropin.

The mechanisms by which prolonged administration of ACTH causes a decrease in aldosterone secretion were studied in the rat. After 6 days of treatment with ACTH (2 U/day), blood corticosterone was elevated and plasma aldosterone was decreased in rats maintained on either a normal or low sodium diet. PRA was also decreased, probably secondary to increased sodium and/or fluid retention. In collagenase-dispersed glomerulosa cells from adrenals of ACTH-treated rats, angiotensin II receptors were markedly decreased, as were the in vitro aldosterone responses to angiotensin II, ACTH, 8-bromo-cAMP, and potassium. However, the production of deoxycorticosterone and precursor steroids was increased, indicating the presence of a block in the late aldosterone biosynthetic pathway. Measurement of the activity of biosynthetic enzymes of the steroidogenic pathway in isolated mitochondria revealed an 80% increase in side-chain cleavage enzyme in both glomerulosa and fasciculata mitochondria from ACTH-treated rats. Although ACTH injection also increased 11-hydroxylase activity in the fasciculata zone, this enzyme was reduced by 50% in capsular mitochondria. The 18-hydroxylase activity in adrenal capsular mitochondria was markedly decreased by ACTH treatment in both normal and sodium-restricted animals. The importance of ACTH-induced steroidogenesis in the development of altered glomerulosa cell function was indicated by the ability of aminoglutethimide to prevent the inhibitory effects of ACTH on angiotensin II receptors and PRA. It is likely that the observed inhibition of the renin-angiotensin system is responsible for the decrease in angiotensin II receptors and 18-hydroxylase, since both are highly dependent on the trophic effect of angiotensin II. The specific lesions produced in adrenal glomerulosa cells by long term ACTH treatment include decreased levels of angiotensin II receptors, 11-hydroxylase, and 18-hydroxylase. These changes are secondary to the suppression of renin-angiotensin activity and are responsible for the impaired aldosterone secretion that results from prolonged treatment with ACTH. (Endocrinology 108: 522, 1981)

Adrenal Glands↗
PubMed1979

The role of cyclic AMP in aldosterone production by isolated zona glomerulosa cells.

The role of cyclic AMP in the regulation of aldosterone production by adrenocorticotropic hormone (ACTH), angiotensin II (A II), potassium, and serotonin was examined in collagenase-dispersed adrenal glomerulosa cells. The ability of 8-bromo cyclic AMP and choleragen to stimulate maximum aldosterone production indicated that cyclic AMP could act as second messenger for certain of the aldosterone-stimulating factors. The actions of ACTH and choleragen on aldosterone and cyclic AMP production were correlated in dog and rat cells, and a similar relation was seen during stimulation of rat cells by serotonin. In contrast, A II and potassium did not cause changes in cyclic AMP formation while stimulating aldosterone production. Intracellular and receptor-bound cyclic AMP were increased 3-fold by 10(-7) M ACTH but not by A II. Addition of a phosphodiesterase inhibitor increased the magnitude of the cyclic AMP response to ACTH but did not change the lack of stimulation by A II or potassium. In dog cells, the effects of A II and potassium on aldosterone production were partially additive to those of ACTH, choleragen, and 8-bromo cyclic AMP. In contrast, no additivity was observed between A II and potassium, or between combinations of the cyclic AMP-dependent stimuli. These results indicate that the actions of ACTH on aldosterone secretion are mediated by cyclic AMP formation, whereas A II and potassium stimulate aldosterone production through an independent mechanism. The lack of additivity between steroid responses to A II and potassium suggests that these factors could share a common mode of action on steroidogenesis in zona glomerulosa cells.

Adrenal Cortex↗
PubMed1979

Hormonal regulation of peptide receptors and target cell responses.

Regulation of plasma membrane receptors for peptide hormones by the prevailing ligand concentration often causes altered target cell function. Receptor number is determined by hormone-induced changes in membrane conformation, irreversible ligand binding, and processing of ligand-receptor complexes during hormone action.

Adenylyl Cyclases↗
PubMed1978

Control of aldosterone secretion during sodium restriction: adrenal receptor regulation and increased adrenal sensitivity to angiotensin II.

The mechanism of increased adrenal sensitivity to angiotensin II during the aldosterone response to sodium restriction was investigated in the rat. Sodium restriction for 36 hr markedly increased the aldosterone-stimulating effect of low-dose (1 ng/min) infusion of angiotensin II and caused enhanced binding of (125)I-labeled angiotensin II to the zona glomerulosa in vivo. Conversely, in vivo binding of (125)I-labeled angiotensin II was significantly decreased after 36 hr of high-sodium intake. In isolated glomerulosa cells, the increased binding of angiotensin II after sodium restriction was shown to result from a significant increase in receptor affinity (+80%) and a smaller increase in receptor concentration (+25%). The corresponding aldosterone responses in dispersed cells showed an increase in sensitivity to angiotensin II, commensurate with the increased receptor affinity. More prolonged sodium restriction (4 days) caused a further increase in angiotensin receptor concentration (+70%) and maximal aldosterone response (+50%), whereas the binding affinity of adrenal receptors and the sensitivity of the in vitro aldosterone response had returned to normal. During sodium loading for 36 hr and 4 days, the converse effects on adrenal angiotensin II receptors and aldosterone production were observed. Also, in contrast to the consistent increase in angiotensin II receptors in the adrenal glands of sodium-restricted animals, the angiotensin II binding capacity of uterine smooth muscle was decreased by 40% after 7 days of sodium restriction.The rapid regulation of receptor affinity and concentration during changes in sodium intake provides a basis for the dynamic modulation of aldosterone responses by dietary sodium content. During sodium restriction, the sequential changes in receptor affinity and concentration account for the enhanced binding and steroidogenic actions of angiotensin II in vivo and in vitro. These receptor changes, and the converse effects of sodium loading, serve as a local regulatory mechanism in the physiological control of adrenal sensitivity and aldosterone secretion. The opposite finding in smooth muscle-that sodium restriction decreases the concentration of angiotensin II receptors-is consistent with the divergent effects of changing sodium balance upon vascular and adrenal responses to angiotensin II.

Adrenal Glands↗
PubMed1978

Regulation of aldosterone secretion by the renin-angiotensin system during sodium restriction in rats.

The role of angiotensin II as mediator of the aldosterone response to short periods of sodium restriction was studied in rats by administration of a converting enzyme inhibitor to block formation of the octapeptide throughout the duration of decreased sodium intake. In control animals, short-term sodium restriction caused increased levels of adrenal receptors for angiotensin II, with enhancement of early and late steps in aldosterone biosynthesis and elevation of plasma aldosterone concentration. Each of these changes induced by sodium deficiency was abolished during blockade of angiotensin II formation by continuous infusion of the converting enzyme inhibitor, SQ 14,225. The absolute dependence of adrenal glomerulosa cell responses on angiotensin II formation indicates that the renin-angiotensin system is the primary regulator of aldosterone secretion during physiological fluctuations in sodium intake.

Adrenal Glands↗
PubMed1978

Angiotensin II receptors and aldosterone production in rat adrenal glomerulosa cells.

Specific receptors for angiotensin II (A II) were demonstrated in membrane fractions and collagenase-dispersed cells from the zona glomerulosa of the rat adrenal gland. The equilibrium association constant (Ka) of the A II binding sites was similar in particulate fractions (2.0 +/- 0.4 (SE) X 10(9) M-1) and intact glomerulosa cells (1.8 +/- 0.3 X 10(9) M-1). Specific binding of [125I]iodo-A II was enhanced by increasing sodium concentration, and in the presence of dithiothreitol, EDTA, and EGTA. Plasma membrane fractions prepared by density gradient centrifugation showed increased binding of [125I]iodo-A II, and were correspondingly enriched in adenylate cyclase and sodium-potassium-dependent ATPase. Steroid production by collagenase-dispersed adrenal glomerulosa cells was highly responsive to A II and ACTH. Significant increases in aldosterone and corticosterone production were elicited by A II concentrations as low as 3 X 10(-11) M, equivalent to normal blood levels of A II in rats (5 X 10(-11) M). The maximum increase in aldosterone production, of 6--7 times the basal value, was obtained at 10(-9) M A II. Dispersed capsular cells were also highly sensitive to ACTH, responding to concentrations down to 3 X 10(-12) M with increased aldosterone production, reaching a maximum aldosterone response of 20-fold above the basal value. The magnitudes of the aldosterone and corticosterone responses to A II in capsular and fasciculata-reticularis cells were commensurate with the distribution of A II receptors, which were 11-fold more concentrated in capsular cells. The ability of A II to evoke aldosterone production at physiological concentrations, and the correspondence between A II binding and steroidogenesis in capsular cells, demonstrate the functional importance of A II receptor sites in the zona glomerulosa of the rat adrenal cortex.

Adrenal Glands↗
PubMed1978

Further studies on the relationship between potassium and sodium levels and adrenocortical activity.

Steroid production in vitro by dog adrenal cortical slices was measured in the presence of varying concentrations of sodium and potassium ions. Increasing concentrations of potassium produced a significant increase in the intracellular potassium content and in the rate of synthesis of aldosterone. However, the potassium effect on aldosterone secretion may also occur without changes in tissue potassium content. Ouabain significantly diminished intracellular potassium content, but inhibited aldosterone production only at the high dose of 2.5 X 10(-3) M in the presence of an elevated external potassium level. Physiological changes in sodium concentration can modify aldosterone production. The effect was observed with changes as small as 10 mEq/liter sodium. Changes in external potassium and sodium levels modulate aldosterone as well as corticosterone, but not cortisol production. No changes in the intracellular content of potassium were detectable in angiotensin-stimulated tissue. Nevertheless, high doses of ouabain blocked angiotensin-stimulated aldosterone production without affecting cortisol production. The dissociation observed between intracellular potassium levels and aldosterone production suggests that there is not a simple relationship between the two parameters.

Adrenal Cortex↗