Characterization of the alpha 1-adrenoceptor-mediated responses in perfused rat liver.
The present work aimed to further characterise the hepatic alpha 1-adrenergic actions by studying the influence of nutritional status and/or extracellular medium composition in the alpha 1-adrenoceptor-induced responses. The experiments were performed in a non-recirculating liver-perfusion system featuring continuous monitoring of vascular resistance, as well as the effluent perfusate changes in pO2, pCa2+, pK+ and pH. The alpha 1-adrenoceptor activation produced biphasic responses to most parameters studied. The acute phase lasted for about 3 min and it was followed by a phase of sustained stimulation that lasted as long as the receptor activation was maintained. Our data indicate that there is not a single pattern of alpha 1-adrenergic responses but variable patterns depending on the nutritional status and the experimental conditions. Gluconeogenic substrates alone produced reciprocal changes in the outflow perfusate pH and Ca2+ activity. The magnitude of these changes indicates that the diversity of alpha 1-adrenoceptor responses are the result of the superposed effects of different rates of substrates and/or metabolites transport. The sustained alpha 1-adrenoceptor stimulation produced extracellular acidification and increases in respiration, vascular resistance and Ca2+ release. These responses required physiological extracellular [Ca2+]. At low extracellular [Ca2+], the alpha 1-adrenoceptor activation failed to acidify the extracellular medium, suggesting that receptor-induced H+ efflux demands normal rates of Ca2+ influx. The correlation between alpha 1-adrenergic-induced increase in O2 uptake and Ca2+ release indicates that the increased energy production can be accounted for by the energy cost of Ca2+ release. The alpha 1-agonist concentration-response studies have shown significant differences in the [alpha 1-agonist]0.5 for each type of response, suggesting the existence of multiple alpha 1-adrenoceptor-coupled signal-transduction pathways.
Urcelay
E
E
Endocrine Physiology Unit, Centro de Investigaciones Biológicas, C.S.I.C., Madrid, Spain.
Butta
N
N
Arias-Salgado
M J
MJ
Ayuso
M S
MS
Parrilla
R
R
D000818:Animals; D005943:Gluconeogenesis; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009752:Nutritional Status; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*
D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine