Comparison of responses to adrenomedullin and calcitonin gene-related peptide in the pulmonary vascular bed of the cat

DeWitt, Bracken J.; Cheng, David Y.; Caminiti, Gregory N.; Nossaman, Bobby D.; Coy, David H.; Murphy, William A.; Kadowitz, Philip J.

doi:10.1016/0014-2999(94)90143-0

Cited by 56 publications

(13 citation statements)

References 10 publications

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“…Although the expression of AM has not been observed in the normal brain (1,2), the effects of AM on rat pial arteries in situ and on canine basilar arteries in vitro demonstrated the similar vasodilation function of AM in the brain as in the non-central nervous system vasculature (1,(3)(4)(5)(6). i.v.…”

Section: Resultsmentioning

confidence: 99%

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Discovery of adrenomedullin in rat ischemic cortex and evidence for its role in exacerbating focal brain ischemic damage.

Wang

Yue

Barone

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

184

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Focal brain ischemia is the most common event leading to stroke in humans. To understand the molecular mechanisms associated with brain ischemia, we applied the technique of mRNA differential display and isolated a gene that encodes a recently discovered peptide, adrenomedullin (AM), which is a member of the calcitonin gene-related peptide (CGRP) family. Using the rat focal stroke model of middle cerebral artery occlusion (MCAO), we determined that AM mRNA expression was significantly increased in the ischemic cortex up to 17.4-fold at 3 h post-MCAO (P < 0.05) and 21.7-fold at 6 h post-MCAO (P < 0.05) and remained elevated for up to 15 days (9.6-fold increase; P < 0.05). Immunohistochemical studies localized AM to ischemic neuronal processes, and radioligand (12II-labeled CGRP) displacement revealed high-affinity (IC50 = 80.3 nmol) binding of AM to CGRP receptors in brain cortex. The cerebrovascular function of AM was studied using synthetic AM microinjected onto rat pial vessels using a cranial window or applied to canine basilar arteries in vitro. AM, applied abluminally, produced dosedependent relaxation of preconstricted pial vessels (P < 0.05). Intracerebroventricular (but not systemic) AM administration at a high dose (8 nmol), prior to and after MCAO, increased the degree of focal ischemic injury (P < 0.05). The ischemia-induced expression of both AM mRNA and peptide in ischemic cortical neurons, the demonstration of the direct vasodilating effects of the peptide on cerebral vessels, and the ability of AM to exacerbate ischemic brain damage suggests that AM plays a significant role in focal ischemic brain injury.Adrenomedullin (AM) is a recently discovered peptide that was initially identified from human pheochromocytoma (1). Biologically active AM consists of 52 amino acids in humans and 50 amino acids in rats (1, 2), and both AMs exhibit potent vasodilator activity in vitro and in vivo (3-6). AM bears homology to a family of peptides that includes calcitonin gene-related peptide (CGRP) (7-10) and amylin (11,12). CGRP is a widely distributed neuropeptide best known for its potent vasodilator actions (13-15) and its effect on insulin functions (16). Amylin is the major protein found in islet amyloid (11, 16) in humans with non-insulin-dependent diabetes mellitus. CGRP and amylin have been found to have a wide range of biological activities, including energy metabolism, central nervous system and cardiovascular functions, and calcium metabolism (for review see refs. 16 and 17). In contrast, little is known of the biological function of AM beyond vasodilation. In contrast to CGRP, AM mRNA and peptide have not been detected in normal brain (1, 2). Very recently, AM has been associated with congestive heart failure, since elevated levels of AM were found in cardiac tissue of the failing hearts (18).In the present report, we used a recently developed mRNA differential display technique (19) to identify genes expressedThe publication costs of this article were defrayed in part by page charge payment. Th...

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Section: Resultsmentioning

confidence: 99%

“…Biologically active AM consists of 52 amino acids in humans and 50 amino acids in rats (1,2), and both AMs exhibit potent vasodilator activity in vitro and in vivo (3)(4)(5)(6). AM bears homology to a family of peptides that includes calcitonin gene-related peptide (CGRP) (7)(8)(9)(10) and amylin (11,12).…”

mentioning

confidence: 99%

Discovery of adrenomedullin in rat ischemic cortex and evidence for its role in exacerbating focal brain ischemic damage.

Wang

Yue

Barone

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

184

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“…3 fmol ml-', Kitamura et al, 1994a), and in several species has been shown to have potent actions in the vasculature both in vivo and in vitro. For example, in the anaesthetized rat (Ischiyama et al, 1993) and cat , intravenous injection of ADM causes a potent and longlasting hypotensive response, and when infused into the intralobar artery of the cat, evokes vasodilatation in the pulmonary circulation (DeWitt et al, 1994;Lippton et al, 1994). In vitro, low doses of ADM evoke vasodilatation in the isolated perfused mesentery of the rat (Nuki et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Interaction of human adrenomedullin _13–52 with calcitonin gene‐related peptide receptors in the microvasculature of the rat and hamster

Hall

Siney

Lippton³

et al. 1995

British J Pharmacology

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1 Adrenomedullin (ADM), a recently discovered circulating hypotensive peptide, shares limited sequence homology with the sensory nerve-derived vasodilator, calcitonin gene-related peptide (CGRP). This study compared the vasodilator effect of sequence 13-52 of human adrenomedullin (ADM,352) with that of human a CGRP (CGRP), in the microvasculature of the hamster cheek pouch and rat skin in vivo.2 Single arterioles (20-40 lim diameter) in the hamster cheek pouch were visualised by intravital microscopy and video recording, and measured by image analysis. Both ADM1352 (1 pmol-0.4 nmol) and CGRP (0.1 pmol-1 nmol) evoked dose-related increases in the diameter of preconstricted arterioles (n = 6). ADM1352 (ED5o 14 pmol) was 20 fold less active than CGRP (ED50 0.71 pmol). The kinetics of onset and decline of vasodilator responses to both peptides were similar, with vasodilator responses to both peptides reaching a maximum at ca. 2 min, and reversing after 10-15 min (n = 5-7). The submaximal increase in blood flow evoked by ADM,3.52 was significantly inhibited (P<0.05; n = 6) by the CGRPI receptor antagonist, CGRP837, at a dose (300 nmol kg-', i.v.) that we have previously shown to inhibit significantly equivalent vasodilator responses to CGRP in this preparation.3 In experiments measuring changes in local blood flow in rat skin by a 133xenon clearance technique, intradermal injection of both ADM,352 (3-300 pmol) and CGRP (0.1-30 pmol) evoked dose-related increases in local blood flow. ADM13.52 (ED50 27 pmol) was 17 fold less potent than CGRP (ED50 1.6 pmol) (n = 6). The submaximal increase in blood flow evoked by both peptides was significantly inhibited (P<0.02; n = 5) by CGRP837 (100 nmol kg-', i.v.).4 We conclude that ADM1352 is a potent vasodilator in the microvasculature of the hamster and rat in vivo. It mediates its vasodilator effect by arteriolar dilatation and this effect is due, at least in part, to the stimulation of CGRPI receptors.

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“…Originally, it was suggested that the cytotrophoblast is the builder of the bridge between mother and fetus; developing along either the syncytiotrophoblast, or extravillous trophoblasts, which possess a more aggressive invasive behavior to provide maternal-fetus interface. ADM is known as a potent vasodilator [28] and an angiogenic factor [46]. It is expressed in many tissues and has the potential to possess more functions such as cell natriuretic, diuretic, and antiapoptosis functions besides vasodilation [31][32][33][34][35][36][37][38][39].…”

Section: Discussionmentioning

confidence: 99%

“…Adrenomedul- lin (ADM) is a polypeptide that was first identified in pheochromocytoma [27]. It belongs to the calcitonin gene-related peptide (CGRP) superfamily [28]. ADM is expressed in several vital organs [29,30] and shows multiple functions [31][32][33][34][35][36][37][38][39].…”

Section: Introductionmentioning

confidence: 99%

Adrenomedullin Enhances Invasion by Trophoblast Cell Lines1

Zhang

Green

Yallampalli

et al. 2005

Biology of Reproduction

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We have tested the hypothesis that adrenomedullin (ADM), a multifunctional peptide hormone, works as a trophoblast proinvasion factor. Our results showed that ADM receptor components-the mRNA and proteins of calcitonin receptor-like receptor (CALCRL) and receptor activity modifying proteins (RAMPs)-were expressed by human choriocarcinoma JAr cells and first-trimester cytotrophoblast HTR-8/SV neo cells. ADM stimulates both JAr and HTR-8/SV neo cell proliferation. The invasion capabilities of JAr cells and HTR-8/SV neo cells were also enhanced by ADM, and this was associated with increased gelatinolytic activity and reduced plasminogen activator inhibitor-1 mRNA expression (SERPINE1). Our data support the notion that ADM may be involved in the human implantation process via regulating trophoblast proliferation and differentiation.

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Comparison of responses to adrenomedullin and calcitonin gene-related peptide in the pulmonary vascular bed of the cat

Cited by 56 publications

References 10 publications

Discovery of adrenomedullin in rat ischemic cortex and evidence for its role in exacerbating focal brain ischemic damage.

Discovery of adrenomedullin in rat ischemic cortex and evidence for its role in exacerbating focal brain ischemic damage.

Interaction of human adrenomedullin _13–52 with calcitonin gene‐related peptide receptors in the microvasculature of the rat and hamster

Adrenomedullin Enhances Invasion by Trophoblast Cell Lines1

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Comparison of responses to adrenomedullin and calcitonin gene-related peptide in the pulmonary vascular bed of the cat

Cited by 56 publications

References 10 publications

Discovery of adrenomedullin in rat ischemic cortex and evidence for its role in exacerbating focal brain ischemic damage.

Discovery of adrenomedullin in rat ischemic cortex and evidence for its role in exacerbating focal brain ischemic damage.

Interaction of human adrenomedullin 13–52 with calcitonin gene‐related peptide receptors in the microvasculature of the rat and hamster

Adrenomedullin Enhances Invasion by Trophoblast Cell Lines1

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Interaction of human adrenomedullin _13–52 with calcitonin gene‐related peptide receptors in the microvasculature of the rat and hamster