Accumulation and inactivation of adenosine by fat cells from hypothyroid rats.

It has been suggested that the deficient lipolytic response to catecholamines in hypothyroidism may be due to an increased sensitivity to adenosine and/or increased adenosine levels in this condition. We confirmed that the addition of adenosine deaminase enhanced the lipolytic response of hypothyroid fat cells, but the stimulation was at least as large in euthyroid cells. Adenosine analogs were more potent as antagonists of NA-induced lipolysis in hypothyroid than in euthyroid fat cells, but the difference could be explained by a decreased response to NA. Suspensions of hypothyroid cells accumulated more purine nucleosides (115 +/- 20) than did euthyroid cells (48 +/- 8 pmol/30 min/10(5) cells; p less than 0.01). This difference could not be explained by a lower rate of adenosine elimination, which occurred by three different pathways: uptake followed by phosphorylation, uptake followed by deamination and deamination by the serum albumin preparation. Under certain circumstances the latter pathway is of overwhelming importance. Fat cells from mature rats (460-480 g) behaved similarly as cells from young control rats. Thus, the changes induced by hypothyroidism was not due to a developmental change. The results are discussed in relation to earlier findings on the alterations in catecholamine responsiveness in hypothyroidism. It is concluded that an increased influence of adenosine could possibly explain some aspects of altered catecholamine responsiveness. If it does the mechanism is likely to involve an enhanced amount of adenosine rather than an increased sensitivity to adenosine.