Proadrenomedullin N-Terminal 20 Peptide (PAMP), Acting Through PAMP(12–20)-Sensitive Receptors, Inhibits Ca
            <sup>2+</sup>
            -Dependent, Agonist-Stimulated Secretion of Human Adrenal Glands

Belloni, Anna S.; Rossi, Gian Paolo; Andreis, P. G.; Aragona, F; Champion, Hunter C.; Kadowitz, Philip J.; Murphy, William A.; Coy, David H.; Nussdorfer, Gastone G.

doi:10.1161/01.hyp.33.5.1185

Cited by 18 publications

(8 citation statements)

References 26 publications

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“…PAMP20 also suppressed catecholamine release from the human adrenal medulla, but the action was different from that observed in bovine adrenal chromaffin cells (52). PAMP20 suppressed catecholamine release caused by activation of voltage-dependent Ca 2 channels by BayK-8644 or by high K , and by the stimulation of angiotensin II receptors with an IC50 value of 0.1 nmol/l, which was three or four orders lower than the value for suppression of catecholamine release caused by nicotinic receptor stimulation in bovine chromaffin cells or in PC12 cells (24,57).…”

Section: Functions Of Am Pamp20 and Pamp12 Incontrasting

confidence: 67%

“…[ 125 I]PAMP-binding sites have also been demonstrated in the human adrenal medulla by autoradiography (51), and these sites were shown to be displaced by low concentrations (IC50 value of nanomolar order) of PAMP20 and PAMP [12][13][14][15][16][17][18][19][20], but not by AM (52). However, these high-affinity binding sites may not correlate with the regulated exocytosis and synthesis of catecholamines, in which the IC50 value for PAMP20 was of micromolar order (24,26).…”

Section: (A) (B)mentioning

confidence: 99%

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Pathophysiological Function of Adrenomedullin and Proadrenomedullin N-Terminal Peptides in Adrenal Chromaffin Cells

et al. 2003

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zyme that methylates noradrenaline into adrenaline.Acetylcholine liberated from splanchnic nerve terminals induces regulated exocytosis of constituents of chromaffin granules in a Ca 2 -dependent manner. The cholinergic receptor subtypes responsible for catecholamine release differ among species; in cows, nicotinic but not muscarinic stimulation induces catecholamine release (2), while in rats and dogs, both nicotinic and muscarinic stimulation induce catecholamine release (3, 4). In addition, the stimulation of cholinergic receptors increases catecholamine synthesis via the activation of TH, the rate limiting enzyme of catecholamine synthesis (5).In addition to catecholamines, chromaffin cells produce a IntroductionAdrenal medullary cells are endocrine cells embryologically derived from the neural crest, which synthesize and release catecholamines. They are composed of adrenaline chromaffin cells and noradrenaline chromaffin cells with minor populations of small intensely fluorescent cells and ganglionic neurons (1). Both adrenaline and noradrenaline chromaffin cells express catecholamine synthesizing enzymes, tyrosine hydroxylase (TH) and dopamine β-hydroxylase (DBH). Adrenaline cells, but not noradrenaline cells, have phenylethanolamine-N methyl transferase (PNMT), an envariety of peptides including chromogranins, opioid peptides and neuropeptide Y (6, 7), which have unique functions such as regulating catecholamine release (8), regulating antibacterial activity (9), sorting peptides from the trans-Golgi network to dense core secretory granules (10), and regulating cell adhesion (11). Catecholamines and other constituents in the chromaffin granules from chromaffin cells are released by pathophysiological stress. Hypoglycemia, hemorrhage, cold exposure or hypoxia causes exocytotic release directly via activation of chromaffin cells, as well as indirectly via activation of the preganglionic sympathetic fibers innervating chromaffin cells (1).On the other hand, adrenomedullin (AM) is a hypotensive peptide that was originally identified in human pheochromocytoma by monitoring of its action on 3 ,5 -cyclic adenosine monophosphate (cAMP) in platelets (12). The AM level in plasma is altered in various diseases; for example, it is increased in patients with hypertension and normalized by anti-hypertensive therapy, indicating that AM is involved in protection against injury occurring in various pathological conditions (13,14). The precursor of AM, the preproAM gene, also produces another hypotensive peptide, the proadrenomedullin N-terminal 20 peptide (PAMP20) (15). However, the mechanisms of action of these peptides are different. In the perfused rat mesenteric arteries, AM directly dilates vascular smooth muscle via receptor that reacts with calcitonin gene-related peptide (CGRP) (16), whereas PAMP20 inhibits noradrenaline release from sympathetic nerve endings, resulting in vasodilatation (17).These peptides are produced not only in pheochromocytoma, but also in almost all organs of the body, and regulate a variety...

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Section: Functions Of Am Pamp20 and Pamp12 Incontrasting

confidence: 67%

Section: (A) (B)mentioning

confidence: 99%

Pathophysiological Function of Adrenomedullin and Proadrenomedullin N-Terminal Peptides in Adrenal Chromaffin Cells

et al. 2003

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“…The truncated PAMP analog PAMP (12)(13)(14)(15)(16)(17)(18)(19)(20) was a partial agonist that elicited ϳ50% of the maximal vasodilator response to the full-sequence peptide, suggesting that activity was retained when the first 11 amino acids were deleted, but that these residues may be necessary for the full expression of vasodilator activity. Although PAMP (12-20) is a partial agonist in human thymic arteries, this truncated peptide does not inhibit Ca 2ϩ -dependent agoniststimulated aldosterone secretion (2). The reason for the difference in activity is uncertain but may suggest differences in activity of the truncated peptide on receptors in small thymic arteries and in the human adrenal cortex.…”

Section: Discussionmentioning

confidence: 97%

Responses to human CGRP, ADM, and PAMP in human thymic arteries

Champion

Bivalacqua

Pierce

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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. Responses to human CGRP, ADM, and PAMP in human thymic arteries. Am J Physiol Regul Integr Comp Physiol 284: R531-R537, 2003; 10.1152/ajpregu.00337.2002Responses to human CGRP, adrenomedullin (ADM), and proadrenomedullin NH2-terminal 20 peptide (PAMP) were studied in small human thymic arteries. CGRP, ADM, and PAMP produced concentrationdependent vasodilator responses in arteries preconstricted with the thromboxane mimic U-46619. Responses to ADM and PAMP were attenuated, whereas responses to CGRP were not altered by endothelial denudation. Inhibitors of nitric oxide synthase and guanylyl cyclase attenuated responses to ADM and PAMP but not to CGRP. The CGRP1 receptor antagonist CGRP(8-37) attenuated responses to CGRP and ADM but not to PAMP. Responses to CGRP were reduced by SQ-22536 and Rp-cAMPS, inhibitors of adenylyl cyclase and PKA. These data suggest that responses to CGRP and ADM are mediated by CGRP(8-37)-sensitive receptors and that the endothelial ADM receptor induces vasodilation by a nitric oxide-guanylyl cyclase mechanism, whereas a smooth muscle CGRP receptor signals by a cAMP-dependent mechanism. A different endothelial receptor recognizes PAMP and signals by a nitric oxide-dependent mechanism. CGRP1 receptor; vascular endothelium; vascular tone; human thymus ADRENOMEDULLIN (ADM) and proadrenomedullin NH 2 -terminal 20 peptide (PAMP) are distinct products encoded by the ADM gene (20-23). The human form of ADM consists of 52 amino acids and a six-membered ring structure that shares homology with CGRP and amylin (20)(21)(22)(23). PAMP consists of 20 amino acids and does not share the six-membered ring structure (20)(21)(22). ADM was discovered in human pheochromocytoma cells and has been localized in many tissues, including vascular smooth muscle cells and the endothelium (11,13,15,16,20). ADM plasma levels are increased in disorders, such as hypertension, heart and renal failure, and hypoxia, and ADM induces a different spectrum of hemodynamic effects than do nitrovasodilators (8, 12-14, 18, 23, 26, 35). PAMP is found in the NH 2 -terminal portion of the precursor for ADM and has a similar distribution, including vascular smooth muscle and the endothelium (17,20,24,36).

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“…PAMP binding sites are well distinct from AM Rs but have not yet been fully characterized, although recent findings seem to suggest that corticostatin MrgX 2 -R may act as PAMP R (Kamohara et al, 2005;Nothacker et al, 2005). Nevertheless, evidence indicates that PAMP(12-20) behaves as a potent antagonist of PAMP Rs (Belloni et al, 1999).…”

Section: Proadrenomedullin-derived Peptidesmentioning

confidence: 99%

Nonclassic Endogenous Novel Regulators of Angiogenesis

Ribatti

Conconi²,

Nussdorfer³

2007

Pharmacol Rev

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162

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Angiogenesis, the process through which new blood vessels arise from preexisting ones, is regulated by several "classic" factors, among which the most studied are vascular endothelial growth factor ( VEGF) and fibroblast growth factor-2 (FGF- 2). In recent years, investigations showed that, in addition to the classic factors, numerous endogenous peptides play a relevant regulatory role in angiogenesis. Such regulatory peptides, each of which exerts well-known specific biological activities, are present, along with their receptors, in the blood vessels and may take part in the control of the "angiogenic switch." An in vivo and in vitro pro-angiogenic effect has been demonstrated for erythropoietin, angiotensin II (ANG- II), endothelins (ETs), adrenomedullin (AM), proadrenomedullin N-terminal 20 peptide (PAMP), urotensin-II, leptin, adiponectin, resistin, neuropeptide- Y, vasoactive intestinal peptide ( VIP), pituitary adenylate cyclase- activating polypeptide ( PACAP), and substance P. There is evidence that the angiogenic action of some of these peptides is at least partly mediated by their stimulating effect on VEGF ( ANG- II, ETs, PAMP, resistin, VIP and PACAP) and/ or FGF-2 systems ( PAMP and leptin). AM raises the expression of VEGF in endothelial cells, but VEGF blockade does not affect the proangiogenic action of AM. Other endogenous peptides have been reported to exert an in vivo and in vitro antiangiogenic action. These include somatostatin and natriuretic peptides, which suppress the VEGF system, and ghrelin, that antagonizes FGF- 2 effects. Investigations on "nonclassic" regulators of angiogenesis could open new perspectives in the therapy of diseases coupled to dysregulation of angiogenesis

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Proadrenomedullin N-Terminal 20 Peptide (PAMP), Acting Through PAMP(12–20)-Sensitive Receptors, Inhibits Ca ²⁺ -Dependent, Agonist-Stimulated Secretion of Human Adrenal Glands

Abstract: Abstract-Proadrenomedullin

Cited by 18 publications

References 26 publications

Pathophysiological Function of Adrenomedullin and Proadrenomedullin N-Terminal Peptides in Adrenal Chromaffin Cells

Pathophysiological Function of Adrenomedullin and Proadrenomedullin N-Terminal Peptides in Adrenal Chromaffin Cells

Responses to human CGRP, ADM, and PAMP in human thymic arteries

Nonclassic Endogenous Novel Regulators of Angiogenesis

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Proadrenomedullin N-Terminal 20 Peptide (PAMP), Acting Through PAMP(12–20)-Sensitive Receptors, Inhibits Ca 2+ -Dependent, Agonist-Stimulated Secretion of Human Adrenal Glands

Abstract: Abstract-Proadrenomedullin

Cited by 18 publications

References 26 publications

Pathophysiological Function of Adrenomedullin and Proadrenomedullin N-Terminal Peptides in Adrenal Chromaffin Cells

Pathophysiological Function of Adrenomedullin and Proadrenomedullin N-Terminal Peptides in Adrenal Chromaffin Cells

Responses to human CGRP, ADM, and PAMP in human thymic arteries

Nonclassic Endogenous Novel Regulators of Angiogenesis

Contact Info

Product

Resources

About

Proadrenomedullin N-Terminal 20 Peptide (PAMP), Acting Through PAMP(12–20)-Sensitive Receptors, Inhibits Ca ²⁺ -Dependent, Agonist-Stimulated Secretion of Human Adrenal Glands