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G Mazzocchi

Publications and source records attributed to G Mazzocchi.

At least 37 records · Page 2Linked to original sources
PubMed1999

Distribution, functional role, and signaling mechanism of adrenomedullin receptors in the rat adrenal gland.

Adrenomedullin (ADM) is a hypotensive peptide, highly expressed in the mammalian adrenal medulla, which belongs to a peptide superfamily including calcitonin gene-related peptide (CGRP) and amylin. Quantitative autoradiography demonstrated the presence of abundant [125I]ADM binding sites in both zona glomerulosa (ZG) and adrenal medulla. ADM binding was selectively displaced by ADM(22-52), a putative ADM-receptor antagonist, and CGRP(8-37), a ligand that preferentially antagonizes the CGRP1-receptor subtype. ADM concentration-dependently inhibited K+-induced aldosterone secretion of dispersed rat ZG cells, without affecting basal hormone production. Both ADM(22-52) and CGRP(8-37) reversed the ADM effect in a concentration-dependent manner. ADM counteracted the aldosterone secretagogue action of the voltage-gated Ca2+-channel activator BAYK-8644, and blocked K+- and BAYK-8644-evoked rise in the intracellular Ca2+ concentration of dispersed ZG cells. ADM concentration-dependently raised basal catecholamine (epinephrine and norepinephrine) release by rat adrenomedullary fragments, and again the response was blocked by both ADM(22-52) and CGRP(8-37). ADM increased cyclic-AMP release by adrenal-medulla fragments, but not capsule-ZG preparations, and the catecholamine response to ADM was abolished by the PKA inhibitor H-89. Collectively, the present findings allow us to draw the following conclusions: (1) ADM modulates rat adrenal secretion, acting through ADM(22-52)-sensitive CGRP1 receptors, which are coupled with different signaling mechanisms in the cortex and medulla; (2) ADM selectively inhibits agonist-stimulated aldosterone secretion, through a mechanism probably involving the blockade of the Ca2+ channel-mediated Ca2+ influx; (3) ADM raises catecholamine secretion, through the activation of the adenylate cyclase/PKA signaling pathway.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1999

Cerebellin enhances in vitro secretory activity of human adrenal gland.

Cerebellin is a 16-amino acid peptide, originally isolated from rat cerebellum, whose presence has been recently demonstrated in the human adrenal glands and especially in medullary chromaffin cells. Cerebellin concentration dependently increased basal catecholamine (norepinephrine and epinephrine) release by human adrenal slices, containing medullary chromaffin tissue, minimal and maximal effective concentrations being 10(-9) and 10(-7) mol/L. Cerebellin (10(-7) mol/L) markedly enhanced cAMP release by adrenal slices, and the protein kinase A inhibitor H-89 (10(-5) mol/L) blocked catecholamine response to cerebellin. Cerebellin did not affect basal steroid secretion of dispersed human adrenocortical cells, but it concentration dependently increased aldosterone and cortisol production by adrenal slices. Again minimal and maximal effective concentrations were 10(-9) and 10(-7) mol/L. Aldosterone and cortisol responses to 10(-7) mol/L cerebellin was suppressed by both the beta-adrenoceptor antagonist l-alprenolol (10(-6) mol/L) and H-89 (10(-5) mol/L). Collectively, the present findings allow us to conclude that 1) cerebellin exerts a sizable secretagogue action on both cortex and medulla of human adrenals; 2) the peptide directly stimulates catecholamine release via the adenylate cyclase/protein kinase A-dependent signaling pathway; and 3) the mechanism underlying the adrenocortical stimulatory effect of cerebellin is indirect and probably involves the release of catecholamines, which in turn, acting in a paracrine manner, enhance steroid-hormone secretion.

Adrenal Cortex↗
PubMed1999

Guanylin: a novel regulatory peptide possibly involved in the control of Ca2+-dependent agonist-stimulated aldosterone secretion in rats.

Guanylin is a 15-amino acid peptide, which activates guanylate cyclase (GC) and plays a major role in the regulation of water and electrolyte secretion by intestinal mucosa. The expression of guanylin prohormone has been recently demonstrated in the rat adrenal gland, and this prompted us to investigate whether guanylin, like other peptides secreted by adrenal medulla, affects the function of the adrenal cortex. Autoradiography demonstrated the presence of [125I]guanylin binding sites in the zona glomerulosa (ZG), but not zona fasciculata-reticularis. Guanylin did not change either basal or ACTH-stimulated steroid secretion of dispersed rat adrenocortical cells, but concentration-dependently (from 10(-10) M to 10(-8) M) inhibited aldosterone response of ZG (capsular) cells to both angiotensin-II (ANG-II) and K+. Guanylin (10(-8) M) blocked the aldosterone secretagogue effect of the Ca2+-channel activator BAYK-8644, and the Ca2+-ionophore ionomycin counteracted the inhibitory action of this peptide on the secretory responses of capsular cells to ANG-II and K+. As expected, guanylin did not affect cyclic-AMP release by capsular cells, but evoked a sizeable increase in cyclic-GMP production. Both the inhibitor of GMP synthase decoyinine and the GC-inhibitor LY-83583, although suppressing cyclic-GMP release, did not affect guanylin-evoked inhibition of K+-stimulated aldosterone secretion. Collectively, these findings allow us to conclude that guanylin: i) inhibits aldosterone secretion of rat ZG cells by interfering with the agonist-induced activation of voltage-gated Ca2+-channels, the stimulation of guanylate cyclase conceivably playing a negligible role; and ii) could be included in that group of regulatory peptides, secreted by medullary chromaffin cells, which are able to counteract an exceedingly high aldosterone secretion.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1999

Mechanisms and receptor subtypes involved in the stimulatory action of endothelin-1 on rat adrenal zona glomerulosa.

Endothelin (ET)-1 is the prototype of a family of 21-amino acid residue hypertensive peptides, acting through two subtypes of receptors, named ETA and ETB. ETs and their receptors are expressed in the adrenal cortex and medulla, and ET-1 enhances both corticosteroid and catecholamine release. ET-1 concentration-dependently (from 10(-11) to 10(-8) M) increased aldosterone secretion of both dispersed rat zona glomerulosa (ZG) cells and adrenal slices containing a core of medullary chromaffin tissue, but the response of the latter preparations was significantly more intense than that of the formers. The stimulatory effect of 10(-8) M ET-1 on dispersed ZG cells was blocked by the ETB-receptor antagonist BQ-788 (10(-7) M), but not by the ETA-receptor antagonist BQ-123 (10(-7) M); conversely, both ET-receptors antagonists counteracted aldosterone response of adrenal slices to ET-1. The -adrenoceptor antagonist l-alprenolol (10(-6) M) did not affect aldosterone response of dispersed ZG cells to ET-1 (10(-8) M), but it significantly lowered that of adrenal slices. l-Alprenolol also counteracted the aldosterone response of adrenal slices to the pure activation of ETB or ETA receptors, as obtained by using the selective ETB-receptor agonist BQ-3020 (10(-8) M) or ET-1 (10(-8) M) plus BQ-788 (10(-7) M). ET-1 concentration-dependently (from 10(-9) to 10(-8)/10(-7) M) stimulated catecholamine release by adrenal slices, and the effect was counteracted by both BQ-123 and BQ-788 (10(-7) M). Collectively, our findings suggest that, when the integrity of adrenal tissue is preserved, a two-fold mechanism underlies the aldosterone secretagogue action of ET-1 in the rat: i) a direct mechanism mediated by ETB receptors located on ZG cells; and ii) an indirect mechanism involving the ETA and ETB receptor-mediated local release of catecholamines, which in turn stimulate ZG cells in a paracrine manner.

Aldosterone↗
PubMed1998

A local immuno-endocrine interaction may mediate rat adrenal glucocorticoid response to bacterial endotoxins.

The effects of the bacterial endotoxin lipopolysaccharide (LPS) and interleukin (IL)-1beta on corticosterone secretion has been studied in vivo by employing the technique of in situ perfusion of the isolated rat left adrenal gland. Both LPS and IL-1beta dose-dependently raised corticosterone output, the response peaking at 60 and 90 min, respectively. IL-1 receptor antagonist dose-dependently reversed the effect of LPS and IL-1beta. The IL-1beta converting enzyme (ICE) inhibitor Ac-YVAD-CMK annulled the adrenal response to LPS, but did not affect that to IL-1beta. Collectively, these findings provide evidence that LPS, by enhancing adrenal production of IL-1beta, is able to evoke a sizable glucocorticoid response in the rat, thereby suggesting that local immuno-endocrine interactions may be operative in the adrenal gland of this species.

Adrenal Glands↗
PubMed1998

Immune-endocrine interactions in the mammalian adrenal gland: facts and hypotheses.

Several cytokines, which are the major mediators of the inflammatory responses, are well-known to stimulate the hypothalamopituitary corticotropin-releasing hormone (CRH)/adrenocorticotropic hormone (ACTH) system, thereby evoking secretory responses by the adrenal cortex. Many of these cytokines, including interleukin-1 (IL-1), IL-2, IL-6, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (INF-gamma) are synthesized in the adrenal gland by both parenchymal cells and resident macrophages, and the release of some of them (e.g., IL-6 and TNF-alpha) is regulated by the main agonists of steroid hormone secretion (e.g., ACTH and angiotensin-II) and bacterial endotoxins. Adrenocortical and adrenomedullary cells are provided with specific receptors for IL-1, IL-2, and IL-6. IL-1 and TNF-alpha directly inhibit aldosterone secretion of zona glomerulosa cells, whereas IL-6 enhances it. IL-2, IL-3, IL-6, and INF-alpha are able to directly stimulate glucocorticoid production by zona fasciculata and zona reticularis cells, whereas IL-1 exerts an analogous effect through an indirect mechanism involving the stimulation of catecholamine release by chromaffin cells and/or the activation of the intramedullary CRH/ACTH system; again, TNF-alpha depresses glucocorticoid synthesis. IL-6 raises androgen secretion by inner adrenocortical layers. IL-1 enhances the proliferation of adrenocortical cells, and findings suggest that cytokines may control the apoptotic deletion of senescent zona reticularis cells. The relevance of the intraadrenal cytokine system in the fine-tuning of the secretion and growth of the adrenal cortex under normal conditions remains to be explored. However, indirect proof is available that local immune-endocrine interactions may play an important role in modulating adrenal responses to inflammatory and immune challenges and stresses.

Adrenal Glands↗
PubMed1998

Galanin stimulates glucocorticoid secretion in rats through a receptor-dependent activation of the adenylate cyclase/protein kinase A-dependent signaling pathway.

Galanin, a 29-amino acid peptide widely distributed in the central and peripheral nervous systems, was found to induce a concentration-dependent increase in corticosterone secretion and cyclic-AMP release by dispersed rat inner adrenocortical cells (maximal effective concentration, 10(-7) M). The effect of 10(-7) M galanin was blocked by 10(-6) M galantide, a specific antagonist of galanin receptors. Galanin (10(-7) M) also enhanced corticosterone and cyclic-AMP responses of dispersed cells to submaximal but not maximal (10(-9) M) effective concentrations of ACTH, and again this effect was reversed by galantide. The ACTH-receptor antagonist corticotropin-inhibiting peptide (10(-6) M) blocked corticosterone response of dispersed cells to 10(-9) M ACTH but not to 10(-7) M galanin; conversely, the specific protein kinase A inhibitor H-89 (10(-5) M) annulled the secretory response to both ACTH and galanin. In light of these findings, we conclude that galanin stimulates adrenal glucocorticoid secretion in rats, acting through specific receptors, coupled, like those of ACTH, with the adenylate cyclase/protein kinase A-dependent signaling pathway.

Adenylyl Cyclases↗
PubMed1998

Vasoactive intestinal peptide stimulates rat adrenal glucocorticoid secretion, through an ACTH receptor-dependent activation of the adenylate cyclase signaling pathway.

Vasoactive intestinal peptide (VIP) concentration-dependently enhanced corticosterone and cyclic-AMP release by dispersed rat inner adrenocortical cells. A VIP-receptor antagonist and the ACTH-receptor antagonist corticotropin-inhibiting peptide annulled both adrenocortical-cell responses to VIP, while the protein kinase (PKA) inhibitor H-89 blocked only corticosterone response. Collectively, these findings suggest that VIP stimulates glucocorticoid secretion of rat adrenals, through the aspecific activation of ACTH receptors coupled with the adenylate cyclase/PKA-dependent signaling pathway.

Adenylyl Cyclases↗
PubMed1998

11beta-hydroxysteroid dehydrogenase expression and activity in the human adrenal cortex.

Although oxidation of cortisol or corticosterone by 11beta-hydroxysteroid dehydrogenase (11beta-HSD) represents the physiological mechanism conferring specificity for aldosterone on the mineralocorticoid receptor in mineralocorticoid target tissues, little attention has been paid until now to the expression and activity of this enzyme in human adrenals. We have shown that human adrenal cortex expresses 11beta-HSD type 2 (11beta-HSD2) gene, and found a marked 11beta-HSD2 activity in microsomal preparations obtained from slices of decapsulated normal human adrenal cortices. Under basal conditions, adrenal slices secreted, in addition to cortisol and corticosterone (B), sizeable amounts of cortisone and 11-dehydrocorticosterone (DH-B), the inactive forms to which the former glucocorticoids are converted by 11beta-HSD. Addition of the 11beta-HSD inhibitor glycyrrhetinic acid elicited a moderate rise in the production of cortisol and B and suppressed that of cortisone and DH-B. ACTH and angiotensin II evoked a marked rise in the secretion of cortisol and B, but unexpectedly depressed the release of cortisone and DH-B. ACTH also lowered the capacity of adrenal slices to convert [3H]cortisol to [3H]cortisone. This last effect of ACTH was concentration-dependently abolished by both aminoglutethimide and cyanoketone, which blocks early steps of steroid synthesis, but not by metyrapone, an inhibitor of 11beta-hydroxylase. Collectively, these findings indicate that the human adrenal cortex possesses an active 11beta-HSD2 engaged in the inactivation of newly formed glucocorticoids. The activity of this enzyme is negatively modulated by the main agonists of glucocorticoid secretion through an indirect mechanism, probably involving the rise in the intra-adrenal concentration of non-11beta-hydroxylated steroid hormones.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1998

Role of endothelins in regulation of vascular tone in the in situ perfused rat adrenals.

This study examined the role of endothelins (ETs) and their receptor subtypes ETA and ETB in the regulation of vascular tone in the in situ perfused rat left adrenal gland. Endothelin-1 (ET-1), which binds both ETA and ETB receptors, decreased adrenal flow rate of the perfusion medium, and its effect was reversed by the ETA antagonist BQ-123 and enhanced by the ETB antagonist BQ-788. ET-3, which preferentially binds ETB, and the selective ETB agonist BQ-3020 increased adrenal flow rate of perfusate, and their effects were annulled by BQ-788. BQ-123 magnified the effect of ET-3 and did not affect that of BQ-3020. The ETA-mediated decrease and the ETB-mediated rise in the rate of collection of perfusate were abolished by Ro-31-8220, an inhibitor of protein kinase C (PKC), and by N(G)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase (NOS), respectively. Collectively, these findings suggest that ETs can regulate vascular tone in the in situ perfused rat adrenals via both PKC-coupled ETA and NOS-coupled ETB receptors, the activation of which evokes vasoconstriction and vasodilation, respectively.

Adrenal Glands↗
PubMed1998

Proadrenomedullin N-terminal 20 peptide inhibits aldosterone secretion of human adrenocortical and Conn's adenoma cells: comparison with adrenomedullin effect.

Adrenomedullin (ADM) and proadrenomedullin N-terminal 20 peptide (PAMP) are two vasoactive peptides, which are highly expressed in human adrenal gland. Autoradiography showed the presence of abundant [125I]ADM and [125I]PAMP binding sites in both the outer cortex and medulla of human adrenals. ADM, but not PAMP binding was completely displaced by the specific CGRP1 receptor antagonist CGRP(8-37). ADM and PAMP concentration-dependently inhibited angiotensin-II (ANG-II)-stimulated, but not basal aldosterone secretion of dispersed human adrenocortical cells. PAMP was significantly more potent than ADM (IC50, 0.98 x 10(-11) vs. 3.16 x 10(-9) mol/L). CGRP(8-37) abolished the inhibitory action of ADM, without affecting that of PAMP. Qualitatively analogous findings were obtained using aldosteronoma dispersed cells. However, tumor cells were more sensitive than normal adrenocortical cells (IC50 were 1.32 x 10(12) and 1.51 x 10(-9) mol/L for PAMP and ADM, respectively). Moreover, PAMP was found to also depress basal aldosterone secretion (IC50, 4.27 x 10(-11) mol/L). Neither basal nor ANG-II-stimulated cortisol production by both normal and tumorous adrenocortical cells was altered by ADM or PAMP. Collectively, these findings confirm that ADM (CGRP1) and PAMP receptors are present in the human outer adrenal cortex and allow us to draw the following conclusions: 1) because of its potency, PAMP may a better candidate for being considered a physiological regulator of aldosterone secretion than ADM; and 2) under pathological conditions, both peptides may be capable of reversing overproduction of aldosterone.

Adenoma↗
PubMed1998

Paracrine control of steroid hormone secretion by chromaffin cells in the adrenal gland of lower vertebrates.

The adrenal glands of lower vertebrates display a notable intermingling between steroidogenic and chromaffin tissues, which increases from Pisces to Aves. As in mammals, adrenal chromaffin cells contain and release, in addition to catecholamines, serotonin and several peptides, which may affect the secretory activity of steroidogenic cells in a paracrine manner. Stimulatory molecules include serotonin, arginine-vasotocin, tachykinins, vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide and calcitonin gene-related peptide; inhibitory molecules are dopamine, somatotropic hormone-release inhibiting hormone and galanin. Epinephrine and norepinephrine appear to stimulate steroid secretion in Aves and to inhibit it in Pisces, while their action in Amphibia is controversial. Likewise, atrial natriuretic peptide exerts an anti-secretagogue action in Amphibia and a marked secretagogue effect in Pisces and Aves. The effects of opioids (enkephalins and endorphins) have scarcely been investigated and the findings obtained are highly questionable. Compared with the amazing mass of investigations carried out in mammals, studies in lower vertebrates are few, and in large part performed in Amphibia and Aves. It appears that much further work has to be done by comparative endocrinologists to fully clarify the physiological relevance of the functional interactions between chromaffin and steroidogenic cells in the adrenal glands of lower vertebrates.

Adrenal Cortex↗
PubMed1998

The AT2 receptor-mediated stimulation of adrenal catecholamine release may potentiate the AT1 receptor-mediated aldosterone secretagogue action of angiotensin-II in rats.

The role played by AT1 and AT2 receptors in the mediation of angiotensin-II (ANG-II) aldosterone secretagogue action has been investigated in vitro using different types of rat adrenal preparations. ANG-II enhanced aldosterone secretion of dispersed zona glomerulosa (ZG) cells in a concentration-dependent manner (EC50, 3 x 10(-10) M), and its effect was annulled by the AT1-receptor antagonist DuP753 and unaffected by the AT2-receptor antagonist PD123319. ANG-II was significantly more effective in stimulating aldosterone secretion when capsule-ZG and adrenal slices containing medullary chromaffin cells were used (EC50, 1 x 10(-11) M and 7 x 10(-12) M, respectively); moreover, both DuP753 and PD123319 caused partial reversals (intense and moderate, respectively) of the responses to ANG-II, and when added together annulled them. The beta-adrenoceptor antagonist l-alprenolol did not affect aldosterone response to ANG-II of dispersed ZG cells, but exerted a PD123319-like effect on the responses of capsule-ZG and adrenal slices. In light of these findings we conclude that, when the integrity of adrenal tissue is preserved, ANG-II stimulates aldosterone secretion by activating both AT1 and AT2 receptors, the major role being played by AT1 receptors located on ZG cells. The activation of AT2 receptors probably elicits the local release of catecholamines, which in turn enhance aldosterone secretion in a paracrine manner acting through the beta-adrenoceptors with which ZG cells are provided.

Adrenal Glands↗
PubMed1997

Effects of adrenomedullin and proadrenomedullin N-terminal 20 peptide on rat zona glomerulosa cells.

Adrenomedullin (ADM) and proadrenomedullin N-terminal 20 peptide (PAMP) derive from a 185-amino acid prohormone, called preproadrenomedullin, which is highly expressed in rat adrenal medulla. ADM and PAMP did not affect either basal or ACTH-stimulated aldosterone secretion of dispersed rat zona glomerulosa cells In contrast, both peptides markedly suppressed angiotensin-II-stimulated aldosterone production, PAMP being much more effective than ADM (minimal effective concentration, 10(-10) M versus 10(-8) M. IC50, 2.0 +/- 0.17 x 10(-9) M versus 3.1 +/- 0.22 x 10(-8) M; P<0.01. Maximum inhibition, 80% versus 43%, respectively). The inhibitory effect of 10(-7) M ADM was completely reversed by the competitive antagonist of type 1 calcitonin gene-related peptide (CGRP) receptors CGRP(8-37) (10(-6) M), while that of 10(-7) M PAMP did not, thereby suggesting that this last peptide acts through specific receptors. Collectively, these findings may suggest that of the two main preproadrenomedullin derived peptides is PAMP which has probably to be considered a physiologic inhibitor of mineralocorticoid secretion in rats.

Adrenocorticotropic Hormone↗
PubMed1997

Neurotensin stimulates CRH and ACTH release by rat adrenal medulla in vitro.

Neurotensin (NT) is a 13-amino acid peptide, widely distributed in the central and peripheral nervous system, which is able to stimulate the activity of the hypothalamo-pituitary CRH-ACTH system. We investigated by RIA the effect of NT on the release of CRH and ACTH immunoreactivities (ir) by rat adrenal medulla in vitro. NT enhanced the release of both CRH-ir and ACTH-ir, the maximal effective concentration being 10(-8) M. [D-Trp11]-NT, a specific NT receptor antagonist, abrogated the effects of NT. The stimulatory effect of 10(-8) M NT on ACTH-ir release was blocked by alpha-helical-CRH (an antagonist of CRH receptors), thereby suggesting that the enhancement in ACTH secretion is consequent to the stimulation of CRH release. These findings suggest that NT is a stimulator not only of the central (hypothalamo-pituitary), but also of the peripheral (intramedullary), branch of the CRH-ACTH system.

Adrenal Medulla↗
PubMed1997

Arginine-vasopressin stimulates CRH and ACTH release by rat adrenal medulla, acting via the V1 receptor subtype and a protein kinase C-dependent pathway.

Arginine-vasopressin (AVP) is a hypothalamic hormone that, like CRH, stimulates the pituitary release of ACTH, thereby activating adrenal glucocorticoid secretion. Evidence indicates that rat adrenal medulla contains a CRH-ACTH system duplicating that existing at the hypothalamo-pituitary level and involved in the paracrine stimulation of the cortex secretion. Therefore, we investigated by RIA the effect of AVP on the release of CRH and ACTH immunoreactivities (IR) by rat adrenal medulla in vitro. AVP concentration-dependently enhanced the release of both CRH-IR and ACTH-IR, and the effect was blocked by a selective antagonist of the V1 subtype of AVP receptors. The CRH receptor antagonist alpha-helical-CRH partially reversed AVP-evoked rise in ACTH-IR release, without altering either CRH response or basal secretions of CRH and ACTH. The specific inhibitors of protein kinase C Ro31-8220 and calphostin C abolished both CRH and ACTH responses to AVP. In conclusion, our present findings suggest that AVP stimulates intramedullary the CRH-ACTH system, acting via V1 receptors and activating protein kinase C.

Adrenal Medulla↗
PubMed1997

Role of adrenomedullin and related peptides in the regulation of the hypothalamo-pituitary-adrenal axis.

Adrenomedullin (ADM) is a hypotensive peptide, originally isolated from human pheochromocytomas, and then found to be widely distributed in the various body systems. ADM derives from preproadrenomedullin, a 185-amino acid residue prohormone, containing at its N-terminal a 20-amino acid sequence, named proadrenomedullin N-terminal 20 peptide (PAMP). ADM and PAMP immunoreactivities have been detected in the hypothalamo-pituitary-adrenal (HPA) axis of humans, rats, and pigs. Adrenal glands possess binding sites for both ADM and PAMP, the former being mainly of the subtype 1 of calcitonin gene-related peptide (CGRP) receptors. ADM exerts a direct inhibitory action on angiotensin II- or potassium-stimulated aldosterone secretion of zona glomerulosa cells. This effect is mediated by the CGRP1 receptor and its mechanism probably involves the blockade of Ca2+ influx. In contrast, ADM enhances aldosterone production by in situ perfused rat adrenals and human adrenal slices (containing medullary chromaffin cells), again through the activation of CGRP1 receptors. This aldosterone secretagogue effect of ADM is blocked by the beta-adrenoceptor antagonist l-alprenolol, thereby suggesting that it is indirectly mediated by the release of catecholamines by chromaffin cells. The effects of ADM on adrenal glucocorticoid release are doubtful and probably mediated by the increase in adrenal blood flow rate and the inhibition of ACTH release by pituitary corticotropes. The concentrations reached by ADM and PAMP in the blood rule out the possibility that they act on the HPA axis as circulating hormones. Conversely, their content in both adrenal and hypothalamo-pituitary complex is consistent with a paracrine mechanism of action, which may play a potentially important role in the regulation of fluid and electrolyte homeostasis.

Adrenomedullin↗