Pro-angiogenic activity of Urotensin-II on different human vascular endothelial cell populations.

Urotensin-II (U-II), along its receptor UT, is widely expressed in the cardiovascular system, where it exerts regulatory actions under both physiological and pathological conditions. In the present study, human vascular endothelial cells (EC) from one arterious and three venous vascular beds were used to investigate in vitro their heterogeneity in terms of expression of U-II and UT and of angiogenic response to the peptide. Real-time PCR and immunocytochemistry demonstrated the expression of UT, as mRNA and protein, in all the EC populations investigated.

Adrenomedullin stimulates angiogenic response in cultured human vascular endothelial cells: involvement of the vascular endothelial growth factor receptor 2.

In recent years, evidence has accumulated that many endogenous peptides play an important regulatory role in angiogenesis by modulating endothelial cell behavior. Adrenomedullin (AM), one such factor, was previously shown to exert a clearcut proangiogenic effect in vitro when tested on specialized human endothelial cells, such as HUVECs and immortalized endothelial cell lines. In the present study we used normal adult vascular endothelial cells isolated from human saphenous vein to analyze in vitro the role of AM, related to both early (increased cell proliferation) and late (differentiation and self-organization into capillary-like structures) angiogenic events and their relationship with the vascular endothelial growth factor (VEGF) signaling cascade.

Evidence for a paracrine role of endogenous adrenomedullary galanin in the regulation of glucocorticoid secretion in the rat adrenal gland.

Previous investigations have shown that rat adrenocortical cells are provided with galanin receptors, and galanin stimulates glucocorticoid secretion from dispersed cells. The present study aimed to clarify the possible role of galanin in the physiological regulation of rat adrenal secretory activity. Reverse transcription-polymerase chain reaction detected galanin mRNA expression in the adrenal medulla, but not in the cortex.

Galanin enhances corticosterone secretion from dispersed rat adrenocortical cells through the activation of GAL-R1 and GAL-R2 receptors coupled to the adenylate cyclase-dependent signaling cascade.

Galanin is a regulatory peptide, which acts via three subtypes of receptors, named GAL-R1, GAL-R2 and GAL-R3. Reverse transcription-polymerase chain reaction demonstrated the expression of GAL-R1 and GAL-R2, but not GAL-R3 mRNAs in dispersed rat adrenal zona fasciculata-reticularis (inner) cells. The immuno-blockade of GAL-R1 and GAL-R2, but not GAL-R3, decreased the binding of [3H]galanin to dispersed cells, a complete inhibition being obtained only by the simultaneous blockade of both receptor subtypes.

Urotensin-II and its receptor (UT-R) are expressed in rat brain endothelial cells, and urotensin-II via UT-R stimulates angiogenesis in vivo and in vitro.

Urotensin-II (UII), along its receptor UT-R, is widely expressed in the cardiovascular system, where it exerts regulatory actions under both physiological and pathological conditions. Real-time PCR and immunocytochemistry demonstrated the expression of UII and UT-R as mRNA and protein in rat neuromicrovascular endothelial cells (NECs). UII did not affect the proliferation rate of cultured NECs, but exerted a strong angiogenic action in both an in vitro assay on Matrigel and an in vivo assay on chorioallantoic membrane.

Leptin and leptin receptors in the prostate and seminal vesicles of the adult rat.

Leptin is an adipose tissue-secreted hormone that acts via specific receptors (Ob-R), of which six isoforms are at present recognized (from Ob-Ra to Ob-Rf). Ob-Rb is the only isoform able to activate JAK-STAT and MAPK signaling cascades. A large body of evidence suggests that leptin and its receptors are involved in prostate physiology and pathophysiology in humans, but studies on the leptin system in the rat prostate are lacking.

Ouabain chronic infusion enhances the growth and steroidogenic capacity of rat adrenal zona glomerulosa: the possible involvement of the endothelin system.

Ouabain, an inhibitor of the Na+/K+-ATPase, has been reported to affect the secretory activity of the adrenal cortex, and especially of zona glomerulosa (ZG). However, conflicting results were obtained, depending on the experimental condition used since ouabain appears to interact with angiotensin-II (Ang-II) and its action to be influenced by the electrolyte balance. Hence, we investigated the effects of prolonged (4-month) infusion with ouabain on the rat adrenal cortex.

Endogenous ligands of PACAP/VIP receptors in the autocrine-paracrine regulation of the adrenal gland.

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are the main endogenous ligands of a class of G protein-coupled receptors (Rs). Three subtypes of PACAP/VIP Rs have been identified and named PAC(1)-Rs, VPAC(1)-Rs, and VPAC(2)-Rs. The PAC(1)-R almost exclusively binds PACAP, while the other two subtypes bind with about equal efficiency VIP and PACAP.

Urotensin-II and UII-receptor expression and function in the rat adrenal cortex.

Urotensin-II (UII) is a potent hypertensive peptide, which has been recognized as an endogenous ligand of the G protein-coupled receptor (GPR)-14, now named UT-R. Real-time PCR demonstrated the expression of UII and UT-R mRNAs in both dispersed and in vitro cultured rat adrenocortical cells. UII concentration-dependently decreased basal, but not ACTH-stimulated, corticosterone secretion from cultured adrenocortical cells, and the effect was abolished by the UT-R antagonist Palosuran.

In vitro culture on Matrigel favors the long-term maintenance of rat zona glomerulosa-cell differentiated phenotype.

Zona glomerulosa (ZG) cells cultured on plastic within few days dedifferentiate losing their capacity to secrete aldosterone (ALDO) in appreciable amounts. Evidence indicates that extracellular matrix modulates the secretory behavior of adrenocortical cells cultured in vitro. Hence, we compared the morphology and function of rat ZG cells grown on plastic and Matrigel basement membrane matrix (hereinafter Matrigel) for up to 12 days.

Identification and localization of adrenomedullin-storing cardiac mast cells.

Adrenomedullin (AM), a potent vasodilatory hypotensive peptide, is expressed in the heart, where it is known to play a protective action. Light-microscopy immunocytochemistry (ICC) demonstrated the presence of AM immunoreactivity not only in the coronary-vessel wall and ventricular myocytes of the human and rat heart, but also in sparse voluminous cells located in the perivascular space. These cells displayed the same location of toluidine blue-positive mast cells, and electron microscopy ICC showed AM-immunogold staining over the granules of rat cardiac mast cells.

Orexins in the regulation of the hypothalamic-pituitary-adrenal axis.

Orexin-A and orexin-B are hypothalamic peptides that act via two G protein-coupled receptors, named orexin type 1 and type 2 receptors (OX1-Rs and OX2-Rs). The most studied biological functions of orexins are the central control of feeding and sleep, but in the past few years findings that orexin system modulates the hypothalamic-pituitary-adrenal (HPA) axis, acting on both its central and peripheral branches, have accumulated. Orexins and their receptors are expressed in the hypothalamic paraventricular nucleus and median eminence and orexin receptors in pituitary corticotropes, adrenal cortex, and medulla.

Age-dependent decrease in the ghrelin gene expression in the human adrenal cortex: a real-time PCR study.

Numerous lines of evidence indicate that ghrelin, an endogenous ligand of the growth hormone-secretagogue receptor, is expressed in the human and rat adrenal cortex. In this study, we examined whether ghrelin gene expression undergoes changes in the human adrenal cortex during aging. Semi-quantitative real-time reverse transcription-polymerase chain reaction demonstrated a highly significant negative correlation between ghrelin mRNA and age in adrenal cortex of 27 patients (aged from 33 to 82 years), who underwent unilateral adrenalectomy/nephrectomy for kidney cancer.

Orexins stimulate glucocorticoid secretion from cultured rat and human adrenocortical cells, exclusively acting via the OX1 receptor.

Orexins A and B are hypothalamic peptides, that act via two subtypes of receptors, named OX1-R and OX2-R. Rat and human adrenal cortexes are provided with both OX1-R and OX2-R, and we have previously shown that orexin-A, but not orexin-B, enhances glucocorticoid secretion from dispersed adrenocortical cells. Since OX1-Rs preferentially bind orexin-A and OX2-Rs are non-selective for both orexins, the hypothesis has been advanced that the secretagogue effect of orexin-A is exclusively mediated by the OX1-R.

The role of adrenomedullin in angiogenesis.

Adrenomedullin (AM) is a 52 amino acid peptide originally isolated from human pheochromocytoma. It was initially demonstrated to have profound effects in vascular cell biology, since AM protects endothelial cells from apoptosis, promotes angiogenesis and affects vascular tone and permeability. This review article summarizes the literature data concerning the relationship between AM and angiogenesis and describes the relationship between vascular endothelial growth factor, hypoxia and AM and tumor angiogenesis.

Cholecystokinin and adrenal-cortex secretion.

Cholecystokinin, or CCK, is a 33-amino acid peptide, originally considered a gut hormone, that acts via two subtypes of receptors, named CCK1-R and CCK2-R. CCK, along with its receptors, has been subsequently localized in the central nervous system, where it exerts, among other fuctions, antiorexinogenic actions. In this survey, we describe findings indicating that CCK, similar to other peptides modulating food intake (e.

Effects of beacon on the rat pituitary-adrenocortical axis response to stress.

Beacon is a peptide expressed in the rat hypothalamus and adrenal cortex, which is involved in the central regulation of feeding and inhibits basal and agonist-stimulated glucocorticoid secretion from adrenocortical cells. In vivo studies on beacon have not yet been carried out, and therefore we investigated the effects of a subcutaneous (sc) injection of beacon on the response of rat hypothalamo-pituitary-adrenal axis to stress. Handling and sc injection per se elicited a moderate increase in the plasma concentrations of ACTH and corticosterone, which was counteracted by beacon.

Orexins modulate the growth of cultured rat adrenocortical cells, acting through type 1 and type 2 receptors coupled to the MAPK p42/p44- and p38-dependent cascades.

Orexin A and B are hypothalamic peptides that act through two subtypes of receptors named OX1-R and OX2-R. The OX1-R almost exclusively binds orexin-A, whereas OX2-R is non-selective for both orexins. We previously found that rat adrenocortical cells express both orexin-receptor subtypes, and orexin-A stimulates corticosterone secretion from dispersed adrenocortical cells acting via the OX1-R.

Cerebellin in the rat adrenal gland: gene expression and effects of CER and [des-Ser1]CER on the secretion and growth of cultured adrenocortical cells.

Cerebellin (CER) is a regulatory peptide, originally isolated from rat cerebellum, which derives from the cleavage of precerebellin (Cbln), three types of which (Cbln1-3) have been identified in humans and rats. CER is also expressed in several extra-cerebellar tissues, including adrenal gland, and evidence has been provided that CER exerts a modulatory action on human and rat adrenal gland. Hence, we have investigated the expression of Cbln1-3 mRNAs and CER protein-immunoreactivity (IR) in the various zones of rat adrenal glands, and the effects of CER and its metabolite [des-Ser(1)]CER (des-CER) on the secretion and growth of cultured rat adrenocortical cells.

Neuropeptide-Y and Y-receptors in the autocrine-paracrine regulation of adrenal gland under physiological and pathophysiological conditions (Review).

Neuropeptide-Y (NPY) is a 36-amino acid peptide, which belongs, along with peptide YY (PYY), to the pancreatic polypeptide (PP) family. The members of this family of peptides act via G protein-coupled receptors (Rs), six subtypes of which (from Y1- to Y6-R) have been identified. NPY and PYY preferentially bind the Y1-R, Y2-R and Y5-R, while PP mainly acts via the Y4-R.

Ghrelin inhibits FGF-2-mediated angiogenesis in vitro and in vivo.

Recent evidence indicates that ghrelin, an endogenous ligand of the growth hormone secretagogue receptor (GHS-R), is highly expressed in the cardiovascular system, and in this study we addressed the possibility that ghrelin may affect angiogenesis in vitro and in vivo. Reverse transcription-polymerase chain reaction showed that human umbilical vein endothelial cells (HUVECs) express ghrelin and GHS-R mRNAs. Ghrelin inhibited FGF-2-induced proliferation of HUVECs cultured in vitro, the maximal effective concentration being 10(-8) M, and this effect was annulled by the GHS-R antagonist D-Lys3-growth hormone releasing peptide-6.

Adrenomedullin (AM) and AM receptor type 2 expression is up-regulated in prostate carcinomas (PC), and AM stimulates in vitro growth of a PC-derived cell line by enhancing proliferation and decreasing apoptosis rates.

Adrenomedullin (AM) is a hypotensive peptide, that acts via the calcitonin receptor-like receptor (CRLR), whose interaction with the subtypes 2 and 3 of a family of receptor activity-modifying proteins (RAMP) gives rise to two distinct AM receptors, named AM1 and AM2 receptors. AM derives from the post-translational proteolytic cleavage of pro(p)AM, the last step of which involves the conversion of the inactive AM to active AM by the peptidyl-glycine alpha-amidating monooxigenase (PAM). Compelling evidence suggests that AM, in addition to exerting its well-known regulatory action on blood pressure and water and electrolyte balance, also possesses a growth promoting effect in several normal and neoplastic tissues, including human prostate.

Biological fate of tissue-engineered porcine valvular conduits xenotransplanted in the sheep thoracic aorta.

The ideal prosthesis to replace the diseased human aortic valve is not yet available. We have previously shown that porcine acellular aortic-valve conduits, obtained by detergent-enzymatic method, display hemodynamic performances similar to those of their native counterparts. Hence, it seemed worthwhile to ascertain whether these tissue-engineered prostheses can be successfully xenotransplanted.

Effects of leptin and leptin fragments on corticosterone secretion and growth of cultured rat adrenocortical cells.

Compelling evidence indicates that leptin, acting via specific receptors (Ob-Ra and Ob-Rb) modulates adrenocortical-cell secretion. However, the results are controversial, inasmuch as either secretagogue or antisecretagogue effects have been reported. Hence, we decided to study the effects of a 96-h incubation with leptin and leptin fragments 116-130, 150-167, 138-167, 93-105, 22-56 and 26-39 (10(-8) and 10(-6) M) on the secretion and growth of cultured rat adrenocortical cells.

Ghrelin inhibits in vitro angiogenic activity of rat brain microvascular endothelial cells.

Ghrelin, a 28-amino acid peptide originally isolated from rat stomach, is an endogenous ligand of the growth hormone secretagogue receptor (GHS-R). Evidence has been provided that ghrelin and GHS-Rs are highly expressed in the cardiovascular system, including endothelial cells (ECs), of which they regulate the growth in vitro. It, therefore, seemed worthwhile to investigate the effect of ghrelin on in vitro angiogenesis, using cultures of rat ECs derived from brain microvessels (neuromicrovascular ECs, NECs).