QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online December 1, 2006
Journal of Experimental Biology 209, 4966-4973 (2006)
Published by The Company of Biologists 2006
doi: 10.1242/jeb.02595

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Imbrogno, S. Articles by Cerra, M. C. Search for Related Content PubMed PubMed Citation Articles by Imbrogno, S. Articles by Cerra, M. C. Social Bookmarking                         What's this?

Beta3-Adrenoceptor in the eel (Anguilla anguilla) heart: negative inotropy and NO-cGMP-dependent mechanism

S. Imbrogno^1,2, T. Angelone^1,2, C. Adamo², E. Pulerà², B. Tota^2,* and M. C. Cerra^1,2

¹ Departments of Pharmaco-Biology, University of Calabria, 87030, Arcavacata di Rende, CS, Italy
² Departments of Cell Biology, University of Calabria, 87030, Arcavacata di Rende, CS, Italy

^* Author for correspondence at address 2 (e-mail: tota{at}unical.it)

Accepted 16 October 2006

Neuroendocrine regulation of cardiac function involves a population of three types of ß-adrenoceptors (ARs). In various mammalian species, ß1- and ß2-AR stimulation produces an increase in contractility; whereas ß3-AR activation mediates negative inotropic effects. At the moment, nothing is known about the physiological role of ß3-AR in fish.

Using an isolated working heart preparation, we show that a ß3-AR selective agonist BRL₃₇₃₄₄ (0.1-100 nmol l^-1) elicits a dose-dependent negative inotropism in the freshwater eel Anguilla anguilla. This effect was insensitive to the ß1/ß2-AR inhibitor nadolol (10 µmol l^-1), but was blocked by the ß3-AR-specific antagonist SR₅₉₂₃₀ (10 nmol l^-1). The analysis of the percentage of stroke work (SW) variations, in terms of EC₅₀ values, induced by BRL₃₇₃₄₄ alone (10 nmol l^-1), and in presence of SR₅₉₂₃₀ (10 nmol l^-1), indicated a competitive antagonism of SR₅₉₂₃₀. In addition to the classic positive inotropism, the non-specific ß agonist isoproterenol (100 nmol l^-1) induced, in 30% of the preparations, a negative inotropic effect that was abrogated by pre-treatment with SR₅₉₂₃₀, pointing to a ß3-mediated pathway. The BRL₃₇₃₄₄-induced negative inotropic effect was abolished by exposure to a G_i/o proteins inhibitor pertussis toxin (PTx; 0.01 nmol l^-1), suggesting a G_i/o-dependent mechanism. Using L-N5(l-imino-ethyl)ornithine (L-NIO; 10 µmol l^-1), as a nitric oxide (NO) synthase (NOS) blocker and haemoglobin (Hb; 1 µmol l^-1), as a NO scavenger, we demonstrated that NO signalling is involved in the BRL₃₇₃₄₄-induced response. Pre-treatment with either an inhibitor of soluble guanylate cyclase (GC) 1H-(1,2,4) oxadiazolo-(4,3-a)quinoxalin-1-one (ODQ; 10 µmol l^-1), or an inhibitor of the cGMP-activated protein kinase (PKG) KT₅₈₂₃ (100 nmol l^-1), abolished the ß3-dependent negative inotropism, indicating the cGMP-PKG component as a crucial target of NO signalling. Taken together, our findings provide functional evidence for the presence of ß3-like adrenoceptors in the eel Anguilla anguilla heart identifying, for the first time in a working fish heart, the ß3-AR-dependent negative inotropy discovered in mammals.

Key words: catecholamines, teleost, G_i/o proteins, cGMP-dependent protein kinase, autocrine-paracrine regulation, myocardial performance, NOS

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				F. Garofalo, M. L. Parisella, D. Amelio, B. Tota, and S. Imbrogno Phospholamban S-nitrosylation modulates Starling response in fish heart Proc R Soc B, November 22, 2009; 276(1675): 4043 - 4052. [Abstract] [Full Text] [PDF]

				P. C. Mendonca and A. K. Gamperl Nervous and humoral control of cardiac performance in the winter flounder (Pleuronectes americanus) J. Exp. Biol., April 1, 2009; 212(7): 934 - 944. [Abstract] [Full Text] [PDF]

				M. Misfeldt, A. Fago, and H. Gesser Nitric oxide increases myocardial efficiency in the hypoxia-tolerant turtle Trachemys scripta J. Exp. Biol., April 1, 2009; 212(7): 954 - 960. [Abstract] [Full Text] [PDF]