DIFFERENTIATION OF PREADIPOSE CELLS - PARACRINE ROLE OF PROSTACYCLIN UPON STIMULATION OF ADIPOSE-CELLS BY ANGIOTENSIN-II

Prostacyclin (PGI(2)), the major metabolite of arachidonic acid in adi pose tissue, has been shown to play a key role in the process of pread ipose cell differentiation in vitro. Moreover, angiotensin-II (Ang II) is able to induce the production of PGI(2) in suspensions of isolated adipocytes as well as in the interstitial fluid of rat adipose tissue . A possible role of Ang II in the control of the autocrine-paracrine adipogenic effect of PGI(2) has been investigated, using cells of the Ob1771 preadipocyte clonal line cultured in serum-free chemically defi ned medium. Whereas both preadipose and adipose cells were able to pro duce PGI(2) upon exposure to arachidonic acid, only adipose cells were able to do so when challenged with Ang II. In agreement with this obs ervation, the ability of Ang II to induce preadipose cells to differen tiate required the simultaneous presence of differentiated cells. Such coculture experiments show that the promoting effect of Ang II on pre adipose cell differentiation was strongly reduced by aspirin, antibodi es able to neutralize PGI(2), and the AT(2) receptor antagonist PD1231 77, but not by the AT(1) receptor antagonist losartan. Together, these results support Ang II as being able, by means of binding to a recept or of the AT(2) subtype present in adipose cells, to control the adipo genic effect of PGI(2) through a paracrine mode of action.