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Biomedical subjects

G Aguilera

Publications and source records attributed to G Aguilera.

At least 91 records · Page 5Linked to original sources
PubMed1992

Participation of alpha 1-adrenergic receptors in the secretion of hypothalamic corticotropin-releasing hormone during stress.

The role of alpha 1-adrenergic receptors in the secretion of corticotropin-releasing hormone (CRH) during stress was studied by immunohistochemical analysis of the CRH content of the median eminence (ME) after intracerebroventricular (icv) administration of the alpha 1-adrenergic agonist, methoxamine, or the antagonist, prazosin, in rats pretreated with colchicine. Immunohistochemical staining was performed by the peroxidase technique on 40 microns free-floating sections using a polyclonal antibody specific for CRH. In the first experimental model, rats were implanted with icv cannulae and adapted to the experimental conditions by daily handling and icv injection of artificial CSF. Colchicine (75 micrograms) was administered through the cannulae 6 h before the experiment, conditions in which axonal transport was blocked with little change in basal immunostaining. Two hours after immobilization stress or a single injection of methoxamine (100 micrograms, icv), there was a marked decrease in CRH immunoreactivity throughout the ME, reflecting release of the neuropeptide into the portal circulation. The decrease in CRH immunostaining following immobilization was largely prevented by icv injection of the alpha 1-adrenergic antagonist, prazosin. In the second experimental model, rats were sacrificed 48 h after icv colchicine injection, conditions in which colchicine acts as a stressor and causes marked depletion of irCRH from the ME. This chronic effect of colchicine was also partially prevented by administration of prazosin, 400-ng injection 5 min prior to colchicine, followed by a continuous icv mini-pump infusion of prazosin, indicating that alpha 1-adrenergic stimulation contributes to the action of colchicine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Desensitization of the hypothalamic-pituitary-adrenal axis following prolonged administration of corticotropin-releasing hormone or vasopressin.

The responses of the hypothalamic-pituitary-adrenal axis during chronic stress are characterized by normal or slightly elevated plasma ACTH, increased hypothalamic corticotropin-releasing hormone (CRH) and vasopressin secretion, decreased pituitary CRH receptors and hypersensitivity of the ACTH and glucocorticoid responses to a novel stress. To determine the role of CRH and vasopressin in the pituitary hyperresponsiveness to a superimposed stress, pituitary CRH receptors and plasma ACTH responses were measured in rats receiving minipump infusions of CRH or a combination of CRH and vasopressin (VP), 50 ng/min of each for 50 h. Rats were killed by decapitation with or without exposure to ether vapor for 5 min or immobilization for 15 or 30 min, and blood was collected for ACTH and corticosterone determinations. The pituitary CRH receptor concentration measured by binding 125I-Tyr-oCRH, was reduced by 45 and 80% in CRH- and CRH-plus-VP-infused rats, respectively, with no changes in receptor affinity. Acute stress by ether exposure or immobilization had no effect on pituitary CRH receptors. Adrenal weight was significantly increased, and thymus weight decreased in CRH-infused animals, indicating activation of the pituitary adrenal axis. However, in contrast to the responses following chronic stress, the increases in plasma ACTH in response to an injection of 10 micrograms/kg CRH or acute stress were significantly lower in CRH- and CRH-plus-VP-infused rats. Furthermore the content and release of ACTH from quartered pituitaries were also decreased in chronically treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1992

Regulation of intermediate pituitary corticotropin-releasing hormone receptors by dopamine.

It has been shown that chronic cold exposure results in selective CRH receptor up-regulation in the intermediate pituitary. Since the intermediate pituitary is under dopaminergic control, the participation of a dopaminergic mechanism in the effect of cold stress was studied in rats treated with dopaminergic agonists and antagonists. CRH receptors were measured by the binding of radioiodinated Tyr-ovine (o) CRH to neurointermediate pituitary membranes of slide-mounted sections. Cold exposure for 60 h caused the expected increase in CRH binding in neurointermediate lobe membranes. Administration of the dopaminergic agonist bromocriptine did not prevent the effect of cold stress, but increased CRH binding in control rats. The dopaminergic antagonist metoclopramide decreased intermediate pituitary CRH binding in control and cold-exposed rats. Bromocriptine administration for 1-8 days caused a progressive increase in the binding of [125I]Tyr-oCRH in neurointermediate pituitary membranes, despite atrophy of the intermediate zone. Scatchard analysis of the binding data indicated that the changes were due to variations in receptor concentration, without changes in affinity. No changes in anterior pituitary CRH receptors were observed with agonist or antagonist treatment. Autoradiographic analysis of CRH binding after 3 days of treatment with bromocriptine or haloperidol confirmed the results observed in membranes and demonstrated that changes in binding were confined to the intermediate lobe. The functional consequences of the changes in CRH binding were studied by analysis of adenylate cyclase activity in cells and homogenates of intermediate pituitaries of rats treated with bromocriptine. In 18-h cultured intermediate pituitary cells from rats treated with bromocriptine for 3 days, CRH-stimulated cAMP production, measured in the presence of phosphodiesterase inhibitors, was increased to levels only slightly higher than those in cells from control rats. Likewise, CRH-stimulated adenylate cyclase, measured by conversion of [32P]ATP to [32P] cAMP, was not significantly different in homogenates from microdissected intermediate lobes from control and bromocriptine-treated rats. The lack of parallel changes in adenylate cyclase responsiveness suggests only partial receptor coupling, probably reflecting an inhibitory effect of dopamine on components of the adenylate cyclase. This study demonstrates that in contrast to the recognized inhibitory effect on cell division and POMC mRNA expression, dopamine causes up-regulation of CRH receptors in the intermediate pituitary. The qualitatively similar and nonadditive effects of cold stress and dopaminergic agonists suggest that a dopaminergic mechanism may be involved in intermediate pituitary CRH receptor regulation during chronic cold stress.

Animals↗
PubMed1992

Studies on the mechanism of the novel stimulatory effect of angiotensin-II on adenylate cyclase in rat fetal skin fibroblasts.

In contrast to other systems in which angiotensin-II (AII) inhibits adenylyl cyclase, in fetal skin fibroblasts the peptide stimulates cAMP accumulation. The mechanism of this novel effect was studied by analysis of the actions of AII and other regulators on the adenylyl cyclase system in cultured cells. In the presence of phosphodiesterase inhibitors, AII, isoproterenol (ISO), choleratoxin (CTx), and forskolin (Fk) stimulated cAMP accumulation by 2.0 +/- 0.26-, 26 +/- 0.9-, 75 +/- 5.6-, and 88 +/- 3.3-fold, respectively. AII potentiated the stimulatory effect of ISO and CTx by 1.5 +/- 0.1- and 1.25 +/- 0.03-fold, respectively, but had no effect on that of Fk. Preincubation of the cells with PTx did not prevent the stimulatory effect of AII on basal and ISO- and CTx-stimulated cAMP, indicating that the effect of AII was not due to interaction with Gi. Unexpectedly, pretreatment of the cells with PTx for 18 h inhibited cAMP production stimulated by ISO and Fk. Similar inhibition by PTx was observed in adult rat skin fibroblasts, but not in adult human fibroblasts, in which pretreatment with PTx resulted in potentiation of Fk-stimulated cAMP production. ADP ribosylation studies showed that the optical density of the band corresponding to Gs was less than 20% that of Gi and Go in rat fetal cells, suggesting that excess release of the beta-gamma-subunit is responsible for the inhibition of cAMP production by PTx. However, immunoblot analysis of G-proteins showed that the content of Gs alpha was similar to that of Gi alpha and Go alpha in rat and human, fetal and adult cells. In contrast to the effect in intact cells, AII had no effect on basal or stimulated adenylyl cyclase activity in cell homogenates, suggesting that the stimulatory effect observed in intact cells is indirect. The stimulatory action of AII on cAMP production was not blocked by indomethacin, indicating that the effect is not mediated by prostaglandin formation. The stimulation of cAMP by AII was mimicked by 10-min incubation with phorbol 12-myristate 13-acetate (PMA), and prevented after cellular protein kinase-C (PKC) depletion by 4- or 6-h preincubation with PMA. However, the stimulation was not prevented by the PKC inhibitors staurosporine and H7 or 24-h preincubation with PMA, suggesting that the effect is not mediated by a traditional PKC-dependent mechanism.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenylyl Cyclases↗
PubMed1992

[Thoracic ectopic kidney. Report of a case].

We describe a 23 months old boy who presented a clinical picture of bronchial hyperreactivity and a tumoral intrathoracic mass in a plain thorax X-ray, receiving for these reasons, antibiotic therapy during 30 days. Intravenous pyelography and ultrasonography revealed the presence of an ectopic intrathoracic kidney. Since this renal anomaly is usually asymptomatic and do not requires treatment, it is necessary to suspect this abnormality whenever an intrathoracic mass is found.

Diagnosis, Differential↗
PubMed1991

Differential distribution of AT1 and AT2 angiotensin II receptor subtypes in the rat brain during development.

Angiotensin II (AII) receptor subtypes were analyzed in the brains of adult and 2-week-old rats by in vitro autoradiography with 125I-labeled [Sar1,Ile8]AII and competition studies with three AII antagonists: the nonpeptide antagonist, DuP 753, which is specific for AT1 receptors that mediate the calcium-inositol phospholipid signaling actions of AII; and nonpeptide (PD 123177) and peptide (CGP 42112A) antagonists that are selective for AT2 receptors of yet unknown function. In the adult rat brain, DuP 753 inhibited radioligand binding to the circumventricular organs and paraventricular nucleus but not to the lateral septum, subthalamic nucleus, and inferior olive. However, binding of 125I-labeled [Sar1,Ile8]AII in the latter regions was inhibited by the AT2 receptor antagonists PD 123177 and CGP 42112A. These areas showed similar displacement by the AT2 receptor subtype-specific antagonists in 2-week-old rats. In addition, radioligand binding at multiple sites of transient expression of AII receptors in 2-week-old rats, including several thalamic nuclei, the nuclei of the 3rd and 12th cranial nerves, geniculate bodies, cerebellum, and cingulate cortex, was displaced by the AT2 antagonists but not by DuP 753. These studies have demonstrated the presence of two AII receptor subtypes in the brain, one (AT1) in areas related to regulation of blood pressure, water intake, and pituitary hormone secretion, and one (AT2) whose function is not yet defined. The abundance and location of brain AT2 receptors in young animals, and the age-related changes in relative expression of the receptor subtypes, suggest that AII exerts specific actions according to the developmental stage of the central nervous system.

Aging↗
PubMed1991

Angiotensin II receptor-mediated proliferation of cultured human fetal mesangial cells.

Accumulating evidence suggests that angiotensin II (Ang II) may play an important role in renal growth and glomerular development. During nephrogenesis, a complex relationship between the capillary and renal mesangium develops. Since the mesangial cell is a centrally-located pericyte with contractile, endocrine, and immune modulating functions, it may play a unique role in maintaining normal glomerular function. Therefore, we examined whether Ang II affects proliferation of human fetal mesangial cells in vitro and compared these findings to mesangial cells isolated from adult kidney. In these primary isolates, we studied the relationship between Ang II receptors and the mitogenic activity of angiotensin. Scatchard analysis of the binding of 125I[Sar1,Ile8]Ang II to subconfluent cultured human fetal mesangial cells revealed the presence of one class of binding sites with a Kd of 1.25 nM and a Bmax of 70 fmol/1 x 10(5) cells. Ang II receptors on adult mesangial cells had similar binding kinetics with a Kd of 1.6 nM and Bmax of 65 fmol/10(5) cells in subconfluent culture. In subconfluent culture of fetal mesangial cells, Ang II increased [3H]thymidine incorporation by 130% (P less than 0.005). In subconfluent culture of adult mesangial cells, Ang II increased [3H]thymidine incorporation by only 35% (P less than 0.05). In confluent culture of fetal mesangial cells, Ang II receptor number and mitogenic response were reduced. The Ang II antagonist [Sar1,Ile8]Ang II (1 microM) inhibited the mitogenic response of fetal mesangial cells to Ang II. Ang II increased fetal mesangial cell number by 25% (after 4 days) in serum-free medium supplemented with insulin or supplemented with insulin and 1% Nutridoma (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Angiotensin-II receptor subtypes and coupling to signaling systems in cultured fetal fibroblasts.

Angiotensin-II (AII) receptors and their coupling to signaling transduction systems were studied in fetal skin fibroblasts using the receptor subtype-specific antagonists Dup753 (type 1) and PD123177 (type 2). In primary cultures, total binding per cell remained constant from days 2-6 of culture, but after subculture levels were initially decreased, then increased until the cells reached confluence. In freshly isolated cells more than 90% of the receptors were type 2, and only a minor fraction were type 1, findings that are consistent with autoradiographic analyses and membrane binding assays. The proportions tended to reverse during culture, with type 1 receptors accounting for 60-80% and type 2 for 20-40% by day 6 of culture. In secondary culture, subtype 1 was about 50% on day 1 and increased to 70% by day 6. At subsequent passages, the proportion of receptor subtypes remained constant up to 6 days, with 90% being of the type 1 variety and 10% of type 2. Scatchard analysis of binding in the presence of the selective antagonists showed similar binding affinities for both subtypes, and the changes in receptor subtype during culture were due primarily to changes in receptor number. Treatment of primary cultures with actinomycin-D for 24 h prevented the transition from AII receptor type 2 to type 1 by increasing the absolute number of type 2 receptors, suggesting that receptor synthesis is regulated at the posttranscriptional level. Stimulation of the cells with 100 nM AII resulted in increases in inositol phosphate accumulation, an effect that was prevented by the type 1 antagonist, but not by the type 2 antagonist. In contrast with other systems in which AII inhibits adenylate cyclase, in fetal fibroblasts AII stimulate cAMP production. The increases in cAMP were more pronounced in secondary cultures in which type 1 receptor content is higher, and the effect was prevented by the type 1, but not the type 2, antagonists. These findings demonstrate the presence of both AII receptor subtypes in fetal fibroblasts, but only the type 1 receptors are coupled to a known intracellular signalling system. The changes in AII receptor subtypes may be the consequence of alterations in intercellular communication, endocrine, or paracrine factors during culture.

Angiotensin II↗
PubMed1990

CRF receptor regulation and sensitization of ACTH responses to acute ether stress during chronic intermittent immobilization stress.

The relationship between corticotropin releasing factor (CRF) receptors and pituitary-adrenal responses was determined after chronic intermittent immobilization (2.5 h restraint/day) to examine the hypothesis that CRF receptor regulation is involved in the sensitization of the pituitary-adrenocortical axis to novel stimuli during repeated stress. Following the 11-fold stimulation of ACTH secretion on the first day of restraint stress, a desensitization of the pituitary ACTH response to immobilization was observed over the next 9 days of chronic intermittent stress. In contrast, the magnitude of the restraint-stimulated release of corticosterone on the 2nd and 4th day of stress was similar to the day 1 adrenocortical response. Furthermore, the significant stimulation of corticosterone secretion by restraint stress persisted to the 16th day of immobilization (P less than 0.001), even though significant increases in plasma ACTH were absent. The concentration of anterior pituitary CRF receptors was unchanged after a single period of restraint; however, a down-regulation of anterior pituitary CRF receptors was observed following 4 days (P less than 0.001) and 10 days (P less than 0.005) of repeated immobilization stress. CRF receptors in the olfactory bulb were unchanged following acute or chronic restraint stress, consistent with previous observations that brain CRF receptors are neither changed by adrenalectomy, glucocorticoid administration, nor 18-48 h of continuous restraint stress. The concentration of CRF receptors in the intermediate lobe of the pituitary also was not influenced by immobilization stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1990

Physicochemical characterization of corticotrophin releasing factor receptor in rat pituitary and brain.

The physicochemical characteristics of solubilized crosslinked CRF receptor-ligand complexes were studied in the anterior and intermediate pituitary lobes and brain of the rat. In all tissues studied, there was a major labeled band with a molecular weight of 72 +2- 3.5 kDa, (n = 15), 71 +/- 1.3 (n = 6), 73 +2- 2.5 (n = 7) and 75 +2- 3.5 (n = 7) kDa in the anterior and intermediate lobes of the pituitary, amygdala and cerebral cortex, respectively. The density of this band was inhibited by CRF analogs, but not by unrelated peptides. This is consistent with the comparable binding properties of CRF in membrane preparations of these tissues. These results suggest that differences in receptor regulation and the reported ability of CRF to stimulate cAMP is due to differences in ligand receptor processing and coupling to membrane transduction systems, rather than to major differences in the binding protein.

Amygdala↗
PubMed1990

Role of protein kinase C on the steroidogenic effect of angiotensin II in the rat adrenal glomerulosa cell.

The role of protein kinase C (PKC) in the steroidogenic action of angiotensin II (AII) was investigated by depletion of endogenous PKC using prolonged incubation with phorbol ester and direct measurement of PKC in isolated rat adrenal glomerulosa cells. PKC activity was measured by incorporation of 32P from [gamma 32P]ATP into histone in the presence of cytosolic and detergent-solubilized membrane fractions purified by diethylaminoethyl cellulose chromatography. Basal PKC activity was higher in cytosol than in membranes (1,000 +/- 57 and 413 +/- 14 pmol P incorporated/mg.min, respectively). After incubation of the cells with AII for 5, 15, 30, and 60 min, PKC activity in the cytosol decreased by 5, 18, 25, and 27%, respectively, while in the membrane there was a transient increase of 15% at 15 min returning to basal by 60 min. Incubation of the cells with 100 nM 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in transient translocation of PKC activity to the membrane (15 min) which was followed by a 64% decrease in total cellular enzyme activity after 3 h. In PKC-depleted cells, the aldosterone response to ACTH was increased by 25% but AII-stimulated steroidogenesis was unchanged. In contrast, in cells in which PKC was translocated to the membrane by a 15 min preincubation with TPA, aldosterone response to AII was enhanced by 40%, while the response to ACTH was reduced by 30%; under these conditions membrane PKC levels rapidly returned to basal. However, the changes in aldosterone response were still evident when addition of AII or ACTH was delayed for up to 30 min after removal of TPA, indicating a persistent modification in the cell membrane secondary to PKC activation. Aldosterone responses to potassium were not altered by preincubation of the cells with TPA. The inactive phorbol ester analog, 4 alpha-hydroxyphorbol-12,13-dibutyrate, had no effect on the steroid responses to either stimulus. The small but significant translocation of PKC activity from cytosol to membrane after treatment of rat adrenal glomerulosa cells with AII suggests that AII activates PKC. However, the fact that aldosterone responses to AII are potentiated during TPA-induced PKC translocation to the membrane suggests that AII and phorbol esters do not share the same mechanism of action in the regulation of steroidogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Aldosterone↗
PubMed1990

Interaction between serotonin and other regulators of aldosterone secretion in rat adrenal glomerulosa cells.

Although serotonin (5HT) is a recognized stimulator of aldosterone secretion in vivo and in vitro, its physiological role as a regulator of mineralocorticoid secretion and its mechanism of action in the adrenal glomerulosa have not been elucidated. To address these questions we studied the interaction of 5HT with other aldosterone regulators in isolated rat adrenal glomerulosa cells. 5HT stimulated aldosterone production 14-fold, with an ED50 of 20 +/- 5 nM, and stimulation was maximal at 0.8 microM. The stimulation of aldosterone production by 5HT was accompanied by a 5-fold increase in cAMP production, with an ED50 of 1 microM. Threshold levels of 5HT (1 nM) potentiated the effect of submaximal concentrations of angiotensin-II (AII), decreasing the ED50 from 1.3 to 0.46 nM and increasing the maximum response in an additive manner. In contrast, the stimulatory effect of 5HT was purely additive to that of submaximal ACTH concentrations. 5HT had no effect on aldosterone secretion stimulated by maximal ACTH concentrations, despite full additivity on cAMP accumulation. Stimulations of steroidogenesis by potassium and 5HT were fully additive at submaximal concentrations, but only partially additive at-maximal levels. To determine the mechanism of the synergistic effects of AII and 5HT, we analyzed the interaction of both stimuli on cAMP accumulation, intracellular calcium, and inositol phosphate formation. Consistent with the inhibitory effect of AII on adenylate cyclase, in the presence of AII the stimulation of cAMP by 5HT was reduced by 18 +/- 3%. 5HT alone had no effect on cytosolic calcium, but significantly enhanced the peak and later phases of the AII-stimulated increase (P less than 0.005). This effect of 5HT was due to calcium influx and not to release from intracellular pools, as shown by suppression of the potentiation in the absence of extracellular calcium and the lack of effect of 5HT on basal or AII-stimulated inositol phosphate formation. The ability of low concentrations of 5HT to potentiate the stimulatory effect of AII on aldosterone secretion suggests that under some physiological conditions, 5HT may play a role in regulating the adrenal sensitivity to AII.

Adrenocorticotropic Hormone↗
PubMed1990

Steroidogenic enzyme activities, morphology, and receptor studies of a testicular adrenal rest in a patient with congenital adrenal hyperplasia.

Steroid-secreting tumors of the testis have generally been considered to be of Leydig cell origin. Testicular tumors in patients with congenital adrenal hyperplasia have been thought to be adrenal rests, but no conclusive evidence supporting the hypothesis has been presented. We report a morphological and biochemical analysis of a patient with 21-hydroxylase deficiency who developed bilateral nodular hyperplasia of steroid-secreting tissue within the testis, despite suppression therapy with both exogenous glucocorticoids and testosterone. The tissue was formed of confluent nodules of homogenous cells. Electron microscopy showed the cells to have abundant smooth endoplasmic reticulum, well developed Golgi apparatus, and mitochondria with predominantly tubular cristae, features characteristic of steroid-secreting cells of adrenocortical origin. Crystals of Reinke were not observed. Functional studies in vivo showed a marked response to ACTH infusion, with 17-hydroxyprogesterone rising from 56 to 13,500 ng/mL, cortisol from less than 2 to 19 micrograms/dL, and testosterone from 369 to 629 ng/dL, with an attendant increase in testicular size and pain over 48 h. Receptor studies in vitro revealed no gonadotropin receptors, but abundant angiotensin-II receptors. Enzyme activity analysis in vitro showed undetectable 21-hydroxylase activity and an enzyme profile consistent with adrenocortical cells rather than Leydig cells. Based on these morphological and biochemical findings, we conclude that the nodular steroidogenic tissue that replaced this patient's testes was of adrenal origin. The study documents for the first time the development of adrenocortical tumors from adrenal rest tissue within the testis.

Adrenal Glands↗
PubMed1990

Characterization and distribution of angiotensin-II receptors in the primate fetus.

The binding characteristics and distribution of angiotensin-II (AII) receptors were studied in Cynomolgus monkey fetuses and one second trimester human fetus. In contrast to the adult monkey, in which binding was confined to the adrenal gland, kidney, and smooth muscle, autoradiographic studies in the monkey fetus revealed the presence of high density binding in mesenchymal tissue throughout the body, especially in skeletal muscle and dermis. In the kidney at 11 weeks, binding was mainly associated with connective tissue surrounding primitive nephrons, while at 17 weeks, binding distribution was similar to that in the adult primate kidney, being confined to the glomeruli and smooth muscle of blood vessels, with low binding in the tubules. In fetal monkey adrenal, binding was high in the medulla and connective tissue of the capsule, and low in the zona glomerulosa, while in the adult, binding was high in the zona glomerulosa and medulla. In membrane preparations from fetal monkey skin and skeletal muscle, binding was specific for AII analogs, but in contrast to the adult adrenal, it was not affected by guanyl nucleotides. Scatchard analysis showed a single class of sites with a Kd of 0.6 +/- 0.1 nM and a capacity of 3060 +/- 8.3 fmol/mg, higher than that of the adult adrenal glomerulosa (605 +/- 30 fmol/mg). Specific binding for AII analogs was also present in human fetal skin and skeletal muscle membranes, where Scatchard analysis indicated a Kd of 0.8 nM and a binding capacity of 640 fmol/mg. The transient expression of abundant AII receptors during the phase of rapid growth in the fetus in conjunction with the known effects of AII on cellular growth suggest a role for AII during fetal development in the primate.

Adrenal Glands↗
PubMed1989

Novel sites of expression of functional angiotensin II receptors in the late gestation fetus.

In the adult, the peptide hormone angiotensin II (AII) is primarily known as a regulator of circulatory homeostasis, but recent evidence also suggests a role in cell growth. This study of AII in late gestation rat fetuses revealed the unexpected presence of receptors in skeletal muscle and connective tissue, in addition to those in recognized adult target tissues. The AII receptors in this novel location decreased by 80 percent 1 day after birth and were almost undetectable in the adult. Studies in fetal skin fibroblasts showed that the receptors were coupled to phospholipid breakdown, with concomitant increases in inositol phosphate and cytosolic calcium. The abundance, timing of expression, and unique localization of functional AII receptors in the fetus suggest a role for AII in fetal development.

Angiotensin II↗
PubMed1989

Inhibitory actions of somatostatin on cyclic AMP and aldosterone production in agonist-stimulated adrenal glomerulosa cells.

Somatostatin (SRIF) is a potent inhibitor of angiotensin II (AII)-stimulated aldosterone production in rat adrenal glomerulosa cells. This inhibition can be prevented by pretreatment of the cells with pertussis toxin, but little else is known about either the specificity or the biochemical bases of SRIF action in this tissue. We therefore conducted detailed studies of the influence of SRIF on steroidogenesis elicited by AII and the other two physiological stimuli of aldosterone production, K+ and adrenocorticotropic hormone (ACTH), in rat adrenal glomerulosa cells. We also determined the effects of SRIF on cytosolic calcium concentration ([Ca2+]i) and cellular cAMP levels. In these studies, SRIF was found to inhibit the aldosterone responses elicited by low concentrations of all three stimuli, which are believed to promote steroid secretion via discrete but interacting cellular signalling mechanisms. In addition, SRIF consistently lowered cellular cAMP levels in the presence of each of the three agents. However, SRIF caused a small and transient increase rather than a decrease in basal ([Ca2+]i), and had no effect on the subsequent elevation of ([Ca2+]i) by AII and K+. These data indicate that activation of a Gi-like protein by SRIF influences steroid responses to all three major regulators of glomerulosa-cell function, and suggest that basal levels of cAMP play a facilitatory or permissive role in the control of aldosterone production by predominantly calcium-mobilizing regulators of mineralocorticoid secretion.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗