Endogenous adenosine inhibits lipolysis induced by nerve stimulation without inhibiting noradrenaline release in canine subcutaneous adipose tissue in vivo.

Abstract

The influence of adenosine on blood flow, lipolysis and adrenergic neurotransmission was studied in canine subcutaneous adipose tissue in situ. Tissue concentrations of endogenous adenosine were elevated in 2 ways: (1) by inhibition of adenosine elimination by i. a. infusion of the uptake blocker dipyridamole (0.5–1.5 μM in arterial plasma) + the deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA; 3–5μM) or (2) by prolonged nerve stimulation (4 Hz for 30 min). Furthermore, effects of exogenous adenosine and the adenosine antagonist theophylline were studied. Dipyridamole+EHNA increased resting vascular conductance from 0.055 to 0.096 ml×min−1×100 g−1×mm Hg−1, whereas lipolysis induced by sympathetic nerve stimulation (2,4 and 8 Hz during 2 min) was inhibited (by 91, 71 and 34%, respectively). “Therapeutic” concentrations of theophylline (5–15 μg/ml plasma) completely reversed the effects of dipyridamole + EHNA on blood flow and significantly reversed the antilipolytic effect of these drugs. In untreated adipose tissue theophylline reduced resting vascular conductance by 40% and enhanced the lipolytic response to prolonged nerve stimulation but not that to brief nerve stimulation. Transmitter release, evaluated by the outflow of endogenous noradrenaline and/or by the outflow of radioactivity after 3H-noradrenaline labelling, was linearly related to the stimulation frequency (2,4 and 8 Hz). Dipyridamole + EHNA increased plasma noradrenaline by inhibiting uptake or binding of noradrenaline to blood cells. However, noradrenaline release induced by nerve stimulation was not significantly affected by dipyridamole + EHNA or by theophylline. It is concluded that a rise in endogenous adenosine concentration caused by drugs or by prolonged sympathetic nerve stimulation inhibits the lipolytic response to nerve stimulation without any effect on noradrenaline release. The results also show that theophylline in a therapeutic dose range is capable of enhancing lipolysis only if endogenous adenosine concentrations are raised.