Impairment of hormone-stimulated cardiac adenylate cyclase activity in the genetically obese (fa/fa) Zucker rat.
The age-related development of the capacity of the cardiac adenylate cyclase system to be stimulated with secretin, vasoactive intestinal peptide (VIP), glucagon, the beta-adrenergic agonist isoproterenol, Gpp(NH)p, and NaF was compared in obese (fa/fa) Zucker rats and their lean (FA/?) littermates. The obese (fa/fa) Zucker rats tested developed postweaning obesity associated with marked hypertriglyceridemia, mild hyperglycemia, and hyperinsulinism. At 4 weeks, there was already a 57% reduction in secretin-VIP-stimulated adenylate cyclase activity in fa/fa rats. At 12 weeks, the secretin-VIP-stimulation was reduced by 77%, and glucagon- and isoproterenol-stimulations by 16-21%. At 45 weeks, secretin-VIP-stimulation was reduced by 91%, glucagon- and isoproterenol stimulations by 34-42%, and Gpp(NH)p- and NaF-stimulations by 16-23%. The reductions of isoproterenol-, Gpp(NH)p-, and NaF-stimulations were totally or partially reversed in 30-week old fa/fa animals submitted for 5 weeks to severe food restriction that almost normalized the altered blood parameters. In sharp contrast, food restriction imposed a further decrease in secretin-VIP- and glucagon-stimulated adenylate cyclase activities. This pattern of impaired secretin-VIP-stimulated adenylate cyclase activity appeared limited to cardiac membranes in obese animals as the responses of liver, brain and anterior pituitary adenylate cyclase activities to secretin and/or VIP were unaltered. These results suggest that secretin-VIP receptors coupled to adenylate cyclase were rapidly and specifically altered in the heart of fa/fa Zucker rats.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000367:Age Factors; D000818:Animals; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D005508:Food Deprivation; D005934:Glucagon / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000201:enzymology*; D009765:Obesity / Q000201:enzymology* / Q000235:genetics; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects*; D012633:Secretin / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D011956:Receptors, Cell Surface; D012633:Secretin; D014660:Vasoactive Intestinal Peptide; D005934:Glucagon; D000262:Adenylyl Cyclases; D007545:Isoproterenol