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Titolo:
EVIDENCE FOR CAMP-INDEPENDENT MECHANISMS MEDIATING THE EFFECTS OF ADRENOMEDULLIN, A NEW INOTROPIC PEPTIDE
Autore:
SZOKODI I; KINNUNEN P; TAVI P; WECKSTROM M; TOTH M; RUSKOAHO H;
Indirizzi:
UNIV OULU,DEPT PHARMACOL & TOXICOL,BIOCTR OULU,KAJAANINTIE 52 D FIN-90220 OULU FINLAND UNIV OULU,DEPT PHARMACOL & TOXICOL,BIOCTR OULU FIN-90220 OULU FINLAND UNIV OULU,DEPT PHYSIOL,BIOCTR OULU FIN-90220 OULU FINLAND SEMMELWEIS UNIV MED,SCH MED,DEPT CARDIOVASC SURG BUDAPEST HUNGARY SEMMELWEIS UNIV MED,SCH MED,DEPT INTERNAL MED 1 BUDAPEST HUNGARY
Titolo Testata:
Circulation
fascicolo: 11, volume: 97, anno: 1998,
pagine: 1062 - 1070
SICI:
0009-7322(1998)97:11<1062:EFCMMT>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
ATRIAL-NATRIURETIC-PEPTIDE; SMOOTH-MUSCLE CELLS; PROTEIN-KINASE-C; CA-2+ RELEASE CHANNEL; HEART-FAILURE; RAT ADRENOMEDULLIN; CYCLIC-AMP; SARCOPLASMIC-RETICULUM; VENTRICULAR MYOCARDIUM; HYPOTENSIVE PEPTIDE;
Keywords:
ADRENOMEDULLIN; CONTRACTILITY; CALCIUM; PEPTIDES; SIGNAL TRANSDUCTION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
59
Recensione:
Indirizzi per estratti:
Citazione:
I. Szokodi et al., "EVIDENCE FOR CAMP-INDEPENDENT MECHANISMS MEDIATING THE EFFECTS OF ADRENOMEDULLIN, A NEW INOTROPIC PEPTIDE", Circulation, 97(11), 1998, pp. 1062-1070

Abstract

Background-Adrenomedullin (ADM), a new vasorelaxing and natriuretic peptide, may function as an endogenous regulator of cardiac function, because ADM and its binding sites have been found in the heart. We characterize herein the cardiac effects of ADM as well as the underlying signaling pathways in vitro, Methods and Results-In isolated perfused, paced rat heart preparation, infusion of ADM at concentrations of 0.1 to 1 nmol/L for 30 minutes induced a dose-dependent, gradual increase in developed tension, whereas proadrenomedullin N-20 (PAMP; 10 to 100 nmol/L), a peptide derived from the same gene as ABM, had no effect. The ADM-induced positive inotropic effect was not altered by a calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP(8-37), or H-89, a cAMP-dependent protein kinase inhibitor. ADM also failed to stimulate ventricular cAMP content of the perfused hearts. Ryanodine (3 nmol/L), a sarcoplasmic reticulum Ca2+ release channel opener, suppressedthe overall ADM-induced positive inotropic effect. Pretreatment with thapsigargin (30 nmoI/L), which inhibits sarcoplasmic reticulum Ca2+ ATPase and depletes intracellular Ca2+ stores, attenuated the early increase in developed tension produced by ADM. In addition, inhibition ofprotein kinase C by staurosporine (10 nmol/L) and blockade of L-type Ca2+ channels by diltiazem (1 mu mol/L) significantly decreased the sustained phase of ADM-induced increase in developed tension. Superfusion of atrial myocytes with ADM (1 nmol/L) in isolated left atrial preparations resulted in a marked prolongation of action potential durationbetween 10 and -50 mV transmembrane voltage, consistent with an increase in L-type Ca2+ channel current during the plateau. Conclusions-Ourresults show that ADM enhances cardiac contractility via cAMP-independent mechanisms including Ca2+ release from intracellular ryanodine-and thapsigargin-sensitive Ca2+ stores, activation of protein kinase C, and Ca2+ influx through L-type Ca2+ channels.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/11/20 alle ore 11:08:54