Regulation of the GTP-binding protein-based antilipolytic system of sheep adipocytes by growth hormone.
Chronic exposure of sheep adipose tissue to growth hormone (GH) in vitro decreases the ability of the adenosine analogue, N6-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, Gi, or the maximum (forskolin-stimulated) adenylate cyclase activity. The ability of GH to modulate the PIA-activated adenosine receptor to stimulate dissociation of heterotrimeric Gi was assessed by measurement of pertussis toxin-catalysed ADP-ribosylation of Gi; GH does not appear to alter the interaction between the activated receptor and Gi. The ability of GH to alter the ability of activated Gi to inhibit adenylate cyclase activity was assessed by measuring the ability of a GTP analogue, guanosine 5'-[beta gamma-imido]triphosphate (p[NH]ppG), to inhibit forskolin-stimulated 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 alpha subunit of one or more isoforms of Gi.
Doris
R A
RA
Hannah Research Institute, Ayr, Scotland, UK.
Kilgour
E
E
Houslay
M D
MD
Vernon
R G
RG
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D046508:Culture Techniques; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D013006:Growth Hormone / Q000494:pharmacology*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007536:Isomerism; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D008954:Models, Biological; D019319:Okadaic Acid / Q000494:pharmacology; D037342:Pertussis Toxin; D010660:Phenylisopropyladenosine / Q000494:pharmacology*; D011485:Protein Binding; D018047:Receptors, Purinergic P1 / Q000187:drug effects*; D012756:Sheep; D013268:Stimulation, Chemical; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D018047:Receptors, Purinergic P1; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D019319:Okadaic Acid; D000246:Adenosine Diphosphate Ribose; D010660:Phenylisopropyladenosine; D006165:Guanylyl Imidodiphosphate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D013006:Growth Hormone; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol