AJP - Cell Physiology, Vol 252, Issue 3 C342-C348, Copyright © 1987 by American Physiological Society
Effect of N6-(L-2-phenylisopropyl)adenosine and insulin on cAMP metabolism in 3T3-L1 adipocytes
M. L. Elks, M. Jackson, V. C. Manganiello and M. Vaughan
The antilipolytic effect of N6-(L-2-phenylisopropyl)-adenosine (PIA), an
adenosine analogue thought to act via cell surface receptors, was
investigated in 3T3-L1 adipocytes. PIA (1 microM) was as effective as 1 nM
insulin in reducing lipolysis stimulated by 1 nM isoproterenol and more
effective than insulin at higher isoproterenol concentrations. In intact
adipocytes, PIA reduced isoproterenol-induced cyclic AMP (cAMP)
accumulation and increased particulate cAMP phosphodiesterase. In
particulate preparations PIA suppressed isoproterenol stimulation of
adenylate cyclase. PIA was more effective than 5'-N-ethylcarboxamide
adenosine (NECA) or adenosine in inhibiting adenylate cyclase and
activating phosphodiesterase. In intact adipocytes, two agents with
so-called "insulin-like" activities, i.e., anti-insulin receptor antibodies
and wheat germ agglutinin (WGA), also increased particulate cAMP
phosphodiesterase. Pertussis toxin, which inhibits stimulation of the
particulate cAMP phosphodiesterase by insulin (but not by isoproterenol),
also inhibited the effects of PIA, anti-insulin receptor antibodies, and
WGA. In 3T3-L1 cells, PIA appears to inhibit lipolysis by inhibiting
adenylate cyclase and stimulating phosphodiesterase; these effects of PIA,
as well as those of anti-insulin receptor antibodies and WGA on
phosphodiesterase, may be mediated via guanyl nucleotide-binding proteins.
