Evidence for a modulating effect of Na+/H+ exchange on the metabolic response of rat brown adipose tissue.
Membrane potential and intracellular pH (pHi) were simultaneously monitored in rat perifused brown adipose tissue fragments by means of double-barrelled microelectrodes. In parallel experiments, the respiratory rate was measured. The cytosolic pH of unstimulated brown adipocytes was about 0.5 units higher than the value expected for a passive transmembrane distribution of H ions. Isoproterenol (5.10(-10)M) had no effect on pHi and membrane potential while it induced a 3.1 +/- 0.5-fold increase of the respiratory rate. Clonidine (10(-7)M) alone was followed by a cytosolic alkalinization of 0.14 +/- 0.05 pH units with no concomitant increase in the respiratory rate. A mirror image of the intracellular alkalinization induced by clonidine, i.e. an acidification of 0.09 +/- 0.03, was noted by monitoring the extracellular pH. Addition of clonidine in the presence of isoproterenol induced an alkalinization of 0.17 +/- 0.03 pH units and a 7.7 +/- 1.0-fold increase of the respiratory rate. Thus the alkalinizing effect of clonidine developed despite a massive increase in CO2 production. Pretreatment of the preparation with amiloride (10(-3)M), an inhibitor of Na+/H+ exchange, completely prevented the alkalinization and markedly reduced the potentiating effect of clonidine on the isoproterenol-induced respiratory rate. The results obtained are compatible with the hypothesis of a modulating effect of Na+/H+ exchange on the brown adipocyte metabolic response to catecholamine stimulation.
Giovannini
P
P
Département de Physiologie, Centre Médical Universitaire, Geneva, Switzerland.
Seydoux
J
J
Girardier
L
L
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007474:Ion Exchange; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D011522:Protons; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism*
D011522:Protons; D000584:Amiloride; D012964:Sodium; D007545:Isoproterenol; D003000:Clonidine