The antilipolytic effect of endogenous and exogenous adenosine in canine adipose tissue in situ

The effects of adenosine, 2-Cl-adenosine, two adenosine uptake inhibitors (dipyridamole and dilazep) and the adenosine deaminase (ADA) inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) were studied on basal and stimulated lipolysis in subcutaneous adipose tissue. The basal lipolysis was unaffected by all agents. Lipolysis induced by nerve stimulation (4 Hz, 5 min) was dose-dependently antagonized (up to 100%) by close i.a. infusions of adenosine (1--40 microM in blood); if the nerve induced vasoconstriction was prevented by alpha-adrenoceptor-blockade. 2-Cl-adenosine was a more potent antilipolytic agent than adenosine. EHNA (3--10 microM in blood) did not inhibit stimulated lipolysis in vivo possibly because of the low ADA activity in fat cells. Dipyridamole (0.5--1.5 microM in blood) in combination with EHNA increased the venous plasma concentration of adenosine from 0.3 +/- 0.05 to 0.7 +/- 0.1 microM and enhanced the tissue concentration close to 3-fold. Lipolysis induced by nerve stimulation (4 Hz) was reduced by about 40% by dipyridamole + EHNA and that induced by close i.a. noradrenaline injection (20 nmol) by approximately 60%. It is concluded that adenosine is an antagonist of stimulated lipolysis in subcutaneous adipose tissue in situ in concentrations that are reached during prolonged sympathetic nerve stimulation.