Chronic exposure of sheep adipose tissue to growth hormone (GH) in vitro decreases the ability of the adenosine analogue, N 6 -phenylisopropyladenosine (PIA), to inhibit isoprenaline-stimulated lipolysis by a mechanism which is dependent on both gene transcription and protein serine/threonine phosphorylation. The inhibition is not due to a change in ligand binding to the adenosine receptor, the amounts of the three isoforms of the inhibitory GTP-binding protein, G i , or the maximum

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... timulated) adenylate cyclase activity. The ability of GH to modulate the PIA-activated adenosine receptor to stimulate dissociation of heterotrimeric G i was assessed by measurement of pertussis toxin-catalysed ADP-ribosylation of G i ; GH does not appear to alter the interaction between the activated receptor and G i . The ability of GH to alter the ability of activated G i to inhibit adenylate cyclase activity was assessed by measuring the ability of a GTP analogue, guanosine 5 -[imido]triphosphate (p[NH]ppG), to inhibit forskolinstimulated adenylate cyclase activity; chronic exposure to GH prevented this effect of p[NH]ppG. Thus the attenuation of the inhibition of lipolysis by PIA by chronic exposure of adipocytes to GH appears to be due to an impairment in the interaction between adenylate cyclase and the subunit of one or more isoforms of G i .