CHARACTERIZATION OF THE ALPHA(1)-ADRENOCEPTOR-MEDIATED RESPONSES IN PERFUSED-RAT-LIVER

Citation
E. Urcelay et al., CHARACTERIZATION OF THE ALPHA(1)-ADRENOCEPTOR-MEDIATED RESPONSES IN PERFUSED-RAT-LIVER, Biochimica et biophysica acta, 1220(1), 1993, pp. 49-56
Citations number
34
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biophysics,Biology
ISSN journal
0006-3002
Volume
1220
Issue
1
Year of publication
1993
Pages
49 - 56
Database
ISI
SICI code
0006-3002(1993)1220:1<49:COTARI>2.0.ZU;2-8
Abstract
The present work aimed to further characterise the hepatic alpha1-adre nergic actions by studying the influence of nutritional status and/or extracellular medium composition in the alpha1-adrenoceptor-induced re sponses. The experiments were performed in a non-recirculating liver-p erfusion system featuring continuous monitoring of vascular resistance , as well as the effluent perfusate changes in pO2, pCa2+, pK+ and pH. The alpha1-adrenoceptor activation produced biphasic responses to mos t parameters studied. The acute phase lasted for about 3 min and it wa s followed by a phase of sustained stimulation that lasted as long as the receptor activation was maintained. Our data indicate that there i s not a single pattern of alpha1-adrenergic responses but variable pat terns depending on the nutritional status and the experimental conditi ons. Gluconeogenic substrates alone produced reciprocal changes in the outflow perfusate pH and Ca2+ activity. The magnitude of these change s indicates that the diversity of alpha1-adrenoceptor responses are th e result of the superposed effects of different rates of substrates an d/or metabolites transport. The sustained alpha1-adrenoceptor stimulat ion produced extracellular acidification and increases in respiration, vascular resistance and Ca2+ release. These responses required physio logical extracellular [Ca2+]. At low extracellular [Ca2+], the alpha1- adrenoceptor activation failed to acidify the extracellular medium, su ggesting that receptor-induced H+ efflux demands normal rates of Ca2influx. The correlation between alpha1-adrenergic-induced increase in O2 uptake and Ca2+ release indicates that the increased energy product ion can be accounted for by the energy cost of Ca2+ release. The alpha 1-agonist concentration-response studies have shown significant differ ences in the [alpha1-agonist]0.5 for each type of response, suggesting the existence of multiple alpha1-adrenoceptor-coupled signal-transduc tion pathways.